Chronic Pain In America

Today's post from updates.pain-topics.org (see link below) illuminates the massive problem of chronic pain, not only in the USA but all across the world. It's enormously costly, has effects on work productivity and social interaction and unless managed properly can directly affect the economy of a country. Why it happens is not discussed here but the fact that such a crisis exists begs the question; what can be done about it and why isn't it a top issue in government circles? Meanwhile, the pharmaceutical industry is not complaining - it's a cash cow for them.

Chronic Pain in America is a National Disgrace
Posted bySB. Leavitt, MA, PhD: Friday, July 1, 2011

Chronic pain affects more than a third of all citizens, it is widely undertreated or mistreated, patients are stigmatized, physicians are inadequately educated, and it costs more than half a trillion dollars each year in medical expenses and lost productivity alone. Those are just a few of the startling findings of a newly released report from the U.S. Institute of Medicine (IOM), which also proposes a multifaceted blueprint for action. The big question is, will something really be done about this public health crisis… and soon?

The 2010 Patient Protection and Affordable Care Act required the U.S. Department of Health and Human Services (HHS) to enlist the IOM in examining pain as a public health problem. The lengthy report, released on June 30, 2011 — Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research — calls for a cultural transformation of attitudes toward pain and its prevention and management. The entire consensus report is available [here].

Among the many noteworthy findings of the 19-member committee assembled by the IOM are the following…
Chronic pain affects an estimated 116 million American adults — more than the total affected by heart disease, cancer, and diabetes combined. This is a much higher number than previously reported [see UPDATE here] and, at that, it may be understated, since it does not include children or people living in institutional settings (eg, nursing homes, prisons). And, as ‘baby boomers’ age, it is expected that the incidence rate of chronic pain will continue to increase.

Pain costs the nation up to $635 billion each year in medical treatments and lost productivity. This, too, is most likely underestimated, since the costs of pain among institutionalized or non-civilian (eg, military) populations were not included. Nor were indirect costs — eg, lost employment, lost tax revenue, costs for replacement workers, etc. — and costs incurred caregivers (eg, family members who miss work while caring for a loved one in pain).

Chronic pain negatively affects socioeconomic status. Whether preventing sufferers from working or interfering with completion of education or training, chronic pain contributes to lower educational and income status, with disproportionate numbers of afflicted persons living below the poverty level.

The report notes that primary care professionals, who manage the bulk of patients with chronic pain, are undertrained and under-staffed for such purposes. Meanwhile, there is a severe scarcity of pain-care specialists and pain facilities to adequately treat patients in need. The IOM report notes that there are only about 3,500 physicians board certified in pain care — equal to 33,000 people with chronic pain for every specialist — and fewer than 200 accredited pain care facilities in all of America. Four out of five patients with severe chronic pain have never been referred to a specialist practitioner or clinic for their conditions.

The IOM panel writes extensively on what they call the “Opioid Conundrum.” While acknowledging that the long-term effects and effectiveness of opioid therapy are uncertain, they also point out that “Federal and state drug abuse prevention laws, regulations, and enforcement practices have been considered impediments to effective pain management….” Among other barriers, they say “Twenty-nine percent of primary care physicians and 16 percent of pain specialists report they prescribe opioids less often than they think appropriate because of concerns about regulatory repercussions.”

The report observes that, “Ironically, while many people with pain have difficulty obtaining opioid medications, nonmedical users appear to obtain them far too easily.” However, the panel also states in italics for emphasis that “the majority of people with pain use their prescription drugs properly, are not a source of misuse, and should not be stigmatized or denied access because of the misdeeds or carelessness of others.”

The IOM committee offers a blueprint for action in transforming prevention, care, education, and research, with the goal of providing relief for people with pain in America. They say that more data and research are needed, and that the nation must adopt a population-level pain prevention and management strategy. At the same time, however, the committee acknowledges that federal dollars for programs and research are “in short supply and likely to decrease.” Still, they state, “Given the burden of pain in human lives, dollars, and social consequences, relieving pain should be a national priority.”

COMMENTARY: The IOM Report is extensively researched, elegantly written, and thought-provoking. Clearly, there is a crisis of chronic pain in America and its long-standing neglect is a scandalous disgrace. The committee recognizes that there are many barriers to pain care, including regulatory, legal, institutional, financial, and geographical — all of them factors that not only limit access to effective pain care but contribute to disparities among select groups, most notably but not exclusively the financially and/or socially disadvantaged.

The committee calls for government agencies, healthcare providers, and public and private funders of health care to adopt a comprehensive, strategic approach to reduce or eliminate the barriers to pain care. However, while this may be rhetorically inspiring, putting such ideology into everyday practice at grass-roots levels is another matter.

It is particularly disconcerting in the report to find a rehash of the usual “doom and gloom” statistics pertaining to the alleged rates of misuse, abuse, diversion, overdose, and mortality associated with opioid analgesics. Many of the data come from surveys and reports that are outdated, inaccurate, and/or biased — a remarkably low quality of evidence — and it was hoped the committee would take a more critical look at the research or at least question its veracity. Apparently, they had neither the time nor inclination to do that; although, their overall perspective on opioids does achieve a measure of balance and they acknowledge certain inequities.

What is most striking in the IOM report is the tremendous toll in human suffering and financial burden inflicted by pain in America. With a third of the population affected directly, and many more when one includes families of persons with pain, this could easily serve as a major campaign platform for eager politicians. A lot of votes could be at stake; so, perhaps someone will take up the cause.

http://updates.pain-topics.org/2011/07/chronic-pain-in-america-is-national.html

Parenting While In Chronic Pain

The final 'self-help' post of the week from theatlantic.com (see link below) looks at dealing with pain when children are involved. Children cannot understand other people's pain the way that adults can and sometimes parents forget that their children may be confused as to why mum or dad is always seeming to be ill and doesn't have enough energy to spend time with them. Children also often try to hide their own needs when it's obvious their parents are having problems and that can't be healthy for them either. This article highlights the problem and may help some parents seek answers to a problem they may have underestimated.

Parenting Through Chronic Physical Pain 
 Rachel Rabkin Peachman Jan 6 2014,

Studies say that when parents are in pain, children suffer. I push my body as hard as I can.

I closed the door on my wailing toddler and left her standing in her crib, reaching out for me. Her cries intensified, like the siren of an ambulance getting closer and louder until its howl drowns out everything else. I walked away and broke down crying. My daughter was sick, and I desperately wanted to soothe her. But I just couldn’t stand and rock her for one more minute to help her get to sleep. My broken body had reached its limit.

I’ve had back pain for much of my life caused by scoliosis, a curvature of the spine. And that afternoon, I felt my back would break if I cradled my daughter’s squirming 25-pound body any longer. I had to give up. My miserable best was to leave the room.

Because of my pain, I was causing my daughter additional suffering—and if recent research is right, this may be only be a harbinger of what’s to come. Experts from Kent State University in Ohio recently did a review of scientific literature examining how children are affected when their parents are in chronic pain. The results, published in the Journal of Child and Adolescent Psychiatric Nursing, are, well, painful to read. It turns out that children whose parents experience chronic pain are at increased risk for adjustment problems and behavioral issues, and are more likely to complain of pain themselves. The whole family suffers. When parents had chronic pain, children often hid their true feelings and needs, and lived in fear of stressing their parents out.

A close look at some of the studies on this topic rocked me to my core. In one study published this month in the Journal of Nursing Scholarship, researchers interviewed a group of 30 adolescents who grew up with parents experiencing chronic pain. In many cases, the children felt their parents were uninvolved physically and/or emotionally, and more likely to be irritable, hostile, and unpredictable. Because of this, the children often hid their true feelings and needs from their parents, lived in fear of stressing their parents out or causing their parents pain, took on a caretaking role before they were ready to do so, and questioned whether they were to blame for their parents’ suffering. The children and young adults dealt with these feelings in various ways—becoming perfectionists, retreating in silence, or turning to substance abuse. Reading these outcomes broke my heart.

Another study—this one published in the Journal of Pain in 2006—compared 39 mothers with chronic pain to 35 pain-free mothers. The mothers with chronic pain reported that they were more likely to be lax in their parenting and that the quality of their relationships with their children suffered compared to mothers without pain. A 2012 study published in Pain examined 3,227 teenagers whose parents had chronic pain. Researchers found that if both parents experienced chronic pain, girls were particularly at risk for anxiety and depression compared to girls whose parents were pain free. What’s more, if it was the mothers who were in pain, girls were also at a greater risk for conduct problems in school.

If that weren’t tough enough to take, two separate studies—one in the Archives of Pediatrics & Adolescent Medicine published in 2012, and another in JAMA Pediatrics published in 2013—assessing 5,370 teens and 8,200 teens respectively, found that children whose parents have chronic pain are at greater risk for feeling chronic pain themselves. Researchers don’t know if this is due to genetics or a learned behavior pattern, but whatever the reason, the children are still in pain.

Before having children, I didn’t consider how my pain might affect my parenting. But one of the many things I couldn’t grasp until I lived it is that being a mother is demanding physical work, especially if you’re one of the 100 million Americans with chronic pain.

For me, the pain developed gradually. From ages eight to 16, I wore a brace under my clothes in an attempt to steady my S-shaped spine. Initially, the hard plastic brace kept my spine in line, like a stern headmaster forcing a malleable student to conform. But the curvature, like an unruly teenager, couldn’t be contained. As an adult, it continued its wayward path, which made pain a constant inhabitant in my body, taking up residence in my back, shoulders, neck, and head. How does a mother suppress her instinct to hold her child when those little arms reach out?

After a strenuous pregnancy with my older daughter (now five), the pain took on a new dimension. Within two years of hoisting my precious cargo into her stroller and high chair, and yes, standing and rocking her to sleep—my body buckled under the strain. Back spasms made it impossible for me to stand or walk for long stretches and sometimes put me out of commission all together. Neck stiffness stopped me from turning my head, shoulder pangs kept me from lifting my arm, and my fingers tingled. I got through my days by popping anti-inflammatory medication, and I spent nights laid up with a heating pad.

Yet whenever my daughter reached for me, I was there with open arms. When my husband was home, he’d often urge me to let him carry her, but all I could think was, “How does a mother suppress her instinct to hold her child when those little arms reach out?”

A scoliosis specialist recommended corrective spinal fusion surgery but after scheduling a surgery date, I learned that the risks of the invasive procedure may not be worth the potential benefits. The surgery would involve cutting open my back, inserting steel rods into my spine, taking a bone graft of my hip, and fusing the vertebrae together to straighten and stabilize the curve. Under the best of circumstances this surgery could lead to complications, cause pain in other areas, and may eventually necessitate a second surgery. Plus, after the operation, I’d barely be able to move for three months, or carry my daughter for a year. Who would dance with her in music class or tuck her into her crib? What if the surgery caused nerve damage, paralysis, or worse? Sure, the physical demands of parenting were backbreaking, but at least I was there to attempt them. I cancelled my surgery date and decided I’d deal with the pain.

Fast-forward a few years—to that afternoon when I couldn’t rock my younger daughter to sleep. My worst symptoms were flaring up, and I couldn’t see how I’d carry us through this time. I sat on the couch, muscles clenched, listening to my toddler cry, distraught that I was of no use to her and could even be causing her harm.

Then, mercifully, she stopped. I checked the baby monitor and saw she’d finally fallen asleep, her arms holding her pink baby doll. My muscles relaxed, and I thought of the pain-free moments I have with my daughters—talking, singing, laughing—moments that strengthen me. I envisioned our cozy weekend mornings, snuggled up, both girls on my lap, enveloped in the soft red blanket that’s big enough to cradle us all.

Science may say the odds are against parents with chronic pain. And I know there are days I’m sidelined and short-tempered. But I’m determined to raise children who feel supported, secure, and loved. I don’t know what my future holds—surgery, therapies, or a lifetime of pain. But I have to believe that despite a deteriorating body, it’s possible to be a successful mother.

I’m still the one my girls reach for—and I refuse to let the pain take that away from me. Motherhood may have weakened my body but my love for my daughters has strengthened my spirit. Per doctor’s orders, I monitor my curve, which has taken us all on a winding ride. And I’m acutely aware that as surely as my curve will grow, so will my children. In a flash, they’ll be older—no longer reaching for me, asking me to carry them, rock them, and hold them. So I push my body beyond its limits now, damn the curve, damn the pain. I carry my girls when I can, rock them for as long as I can, and hold them tight.

http://www.theatlantic.com/health/archive/2014/01/parenting-through-chronic-physical-pain/282543/

Diagnosis Diffculties With Neuropathic Pain

Today's post from articlesnatch.com (see link below) is another article discussing testing procedures and looks at how difficult the whole testing and diagnosis of various forms of neuropathy can be and how a lack of clear results during the testing process can lead to mis-diagnoses.

Diagnostic And Therapeutic Issues Of Neuropathic Pain
By: Sam Edwards

The use of laboratory studies and imaging studies in the diagnosis of neuropathic pain present clinical challenges and, although medications remain the mainstay of therapy, it is frequently necessary to try multiple different medications and modalities for adequate treatment.

There are two types of pain: nociceptive and neuropathic. The former is of a mechanical nature and relates to nerve pain through direct nerve irritation, such as an arthritic joint. The latter implies a specific injury or insult to nerves causing pain and discomfort. Based on my clinical observations in treating patients with neuropathic pain for almost 20 years, it is my belief that neuropathic pain and, in particular, radicular pain has been under-diagnosed and under-treated for a variety of reasons. Partly its our reliance on electrodiagnostic testing in making the diagnosis of radicular pain and the difficulty in obtaining an accurate history from the patient, and an absence of other diagnostic testing to make this diagnosis. Also, health care professionals often overlook the neuropathic component of pain and focus on other causes of chronic pain. Further, the difficulty in the treatment of neuropathic pain presents a clinical challenge.

Neuropathic pain includes, but is not limited to diabetic neuropathy, all peripheral neuropathies, radiculopathy, complex regional pain syndrome, sympathetically mediated pain, fibromyalgia, and interstitial cystitis. A variety of medical conditions that cause peripheral neuropathy include inherited diseases, alcoholism, nutritional vitamin deficiencies, cancers, autoimmune reactions, medications, kidney and thyroid disease and infections such as Lyme disease, shingles or AIDS. Peripheral neuropathy of idiopathic etiology, diabetic peripheral neuropathy, radiculopathy and mono-neuropathies make up the majority of all the causes of neuropathic pain.

Diagnostic Issues
Although the diagnosis of a specific type of neuropathic pain can be complicated, distinguishing between neuropathic pain and nociceptive pain is not as complicated. It is important to distinguish pain patterns in making the diagnosis of neuropathic pain. Practitioners should evaluate the patients as to whether the pain involves an extremity and, if so, is it radiating from the spine or is it a separate pain of a joint or a separate part of the extremity.
Pain location is important and the patient needs to elaborate specifically where the pain occurs. It is helpful to use a pain diagram to show where their pain is located. The practitioner should then go over the diagram with the patient and complete an examination and have the patient show them physically on their body where the pain occurs. If the pain involves an extremity, is it sock-like pain or is it linear in fashion? Are there neurological changes on examination and does the patient have other neurological symptoms or complaints such as numb-ness or tingling?For the purpose of this article, Noxicare Natural Pain Relief examined 30 patients in my clinic with chronic back pain and confirmed compressive pathology in patients who also had extremity pain. Of those 30 patients, only two were able to adequately describe a radicular symptomatology that could be considered as anatomically accurate. Less than half the patients had EMG studies and, of those, about two thirds were reported as negative. In our practice, we have found that the treatment of radicular pain has frequently been denied specifically based on these two issues: that there is a lack of a clear dermatomal pain pattern, and that there is a normal EMG report.

http://www.articlesnatch.com/Article/Diagnostic-And-Therapeutic-Issues-Of-Neuropathic-Pain-/3794002

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Suicide And Chronic Pain Dont Judge!

Today's post from lifeinslowmotionblog.com (see link below) is personally very relevant because this week, I received an email from a man's daughter, who told me that her father had recently taken his own life after 15 years of chronic neuropathic pain. He had been on strong medication for some years. That medication had dulled the pain but never taken it away and he was just tired, both physically and tired of living in constant pain, which impacted so much on the lives of those around him. I decided to see what was written on this subject and if there were reasons why so many people see no other way out than to remove themselves from the equation. Tragically, suicide never does that because the people left behind end up feeling as guilty as the person himself. With all the pressures of life and the message that we should be healthy and productive members of society, suicide numbers may continue to rise as people feel themselves more and more a burden on the people dear to them and on the state that 'supports' them. Legislators should consider very carefully before they blithely remove the drugs that keep people functioning! This article looks at the reasons why so many people in chronic pain, end up taking their own lives. Don't judge...there but for the grace of god go you. If you know of someone in this position, or are in this position yourself, it may be time to read this article and take action!

Understanding Why Individuals with Severe Pain and Illness Die by Suicide. And What We Can Do About It.
Posted on November 7, 2016 by lifeinslowmotion 

It is an undeniable fact that individuals with chronic pain have a higher prevalence rate of suicide than the general population.

Tang and Crane (2006) summarized the results of 12 articles examining correlations between suicide and chronic pain, concluding that individuals with chronic pain are twice as likely to die by suicide than the general population. More specifically, approximately 5-14% of individuals with chronic pain attempt suicide, and about 20% report some level of suicidal ideation.

One of my counseling clients who has experienced chronic pain for the past three years recently told me, “I keep praying that God will take me home as I sleep. I would never kill myself, but I just need a break.” In my work as a counselor, I have found that passive suicidal thoughts such as these are the norm among individuals undergoing constant physical suffering.

Although I have never contemplated suicide, my own experience with chronic pain has been eye-opening regarding how people can get to the place of either active or passive suicidal thoughts. Before pain, the thought of suicide seemed foreign and strange. After dealing with long periods of uncontrolled pain, it is not hard for me to see how people find themselves in a place of hopeless that drifts into suicidal intentions.

I am currently reading a book entitled Myths About Suicide by Thomas Joiner, and it has been eye-opening in understanding some of the finer nuances of why individuals with pain and illness die by suicide. Joiner’s theory is that individuals die by suicide due to the merging of three key factors in their lives: perceived burdensomeness, failed belongingness, and learned fearlessness.

When these three factors converge, individuals are able to move past the ingrained human desire for self-preservation to a place in which death is no longer feared. Not only is death no longer feared, but it becomes seen as a better option than life.

As I considered these three factors, it became apparent why suicide is such an immense risk for individuals facing severe and ongoing illness and pain.

Factor #1: Perceived Burdensomeness

Most individuals with pain or illness feel like a burden. There are so many things we can no longer do and so many tasks others must take over for us. Perhaps we can no longer work and contribute financially. Perhaps, we can’t get around on our own and need constant and close caretaking. Wherever we fall on the spectrum of disability, we can’t shake the feeling that we are burdensome to our families and our friends.

When this feeling of burdensomeness becomes strong enough, individuals begin weighing the costs and benefits of life versus death in terms of how it will affect family and loved ones. They begin to wonder, “Would it be more beneficial for the people around me if I were dead than my current state of being alive?”

Factor #2: Failed Belongingness

Many individuals with severe pain and illness struggle to maintain a sense of belongingness. Joiner describes failed belongingness as “the feeling that one is alienated from others and not an integral part of a family, circle of friends, or other valued group” (Joiner, 2011).

This sense of alienation happens for many reasons among individuals with severe pain and illness. Perhaps most significantly, moving into community becomes difficult to impossible when physical limitations leave individuals bedbound, homebound, or severely limited in their mobility. Many times, groups of people are centered around activities, and those with pain and illness become alienated because they are no longer able to engage in activities that once made them feel as though they belonged.

Friends leave, families drift away, and it becomes difficult to find people to relate to when you aren’t up and doing what everyone else is doing.

Factor #3: Learned Fearlessness

Learned fearlessness is a process of habituation that occurs when individuals go through long-term painful situations.

Joiner explains it this way: “past experience with injury, pain, and the like creates a familiarity and fearlessness, which, if combined with desire for death, can prove fatal” (p. 21).

Individuals with severe pain and illness have no choice but to become acquainted with injury and pain. There is no possible way not to experience it. Over and over again, they are desensitized to physical suffering. The thought of death begins to lose its terror because they have faced so many physical terrors already. In the end, severe and unending pain and illness lead to an erosion of the natural fear of dying.

Some Possible Solutions

Here are some of my initial thoughts on what all this might mean for prevention of suicide among individuals with pain and illness.

When it comes to learned fearlessness, individuals with chronic pain and illness need real relief from their physical and emotional suffering. The process of habituation that occurs due to sustained exposure to severely undermanaged pain and symptoms can often be avoided, to some extent, if physical pain is taken seriously. Patients with pain and illness need doctors and nurses and other medical professionals to believe their pain is real and believe it is actually as bad as they say it is.

They need counselors and friends who will walk with them through their emotional pain, recognizing it as a real and important issue, but not blaming their pain on their emotional status.

They need pain management options and doctors who are willing to try over and over again to bring sustained relief. Individuals with severe pain need opioids and other medicines that are often stigmatized, and they need to be able to take them without being labeled addicts.

Anecdotal evidence reported by the Pain News Network suggests that the new CDC opioid guidelines could be leading to an increase in deaths by suicide among individuals with chronic pain. According to the Pain News Network, many of their readers have written in, explaining that their doctors have decreased or cut off treatment, leading some of them to consider suicide as a better option than years of uncontrolled pain. Something needs to be done.

When it comes to failed belongingness, individuals with chronic pain and illness need real community to welcome them in. Community is so hard to find for individuals with severe pain and illness.

Sometimes it is impossible for them to go into community, and they desperately need community to come to them. They need family, friends, church members, anyone who is willing, to come and be with them.

An acquaintance once approached me several years ago and asked if I needed help with anything. Did I need help getting to doctor’s appointments? Someone to clean my house? Could they do anything for me? I responded that what I actually really needed at that time was company. Would they be willing to come visit me because I was feeling incredibly isolated and unable to get out and be around people. My schedule was flexible, and they could let me know a good time for them.

It was so strange. The moment I asked for this kind of help, the conversation stopped. They never followed up, never said anything further about my request.

Perhaps this was because visiting someone doesn’t necessarily seem like offering help. But it is. It may be the most important thing that can be offered to people isolated because of physical pain and symptoms.

People with severe pain and illness need relief from suffering, but more importantly they need people who will walk with them through their suffering that will not be going away.

When it comes to perceived burdensomeness, individuals with chronic pain and illness need to believe their value does not come from what they are able to do or contribute.

In considering burdensomeness, I think it is important to recognize that burdens do exists. Yes, sometimes we perceive ourselves as burdensome when this is not the case. But, if we are going to deal with this topic honestly, we have to recognize that our pain represents a cost to the people around us.

Yet here is the important difference. You carry a great burden, but you are not a burden. A burden is not who you are, it does not define you. It does not determine your value or your worth.

Every single person who has ever lived will carry burdens, and some people must carry bigger burdens than others. So often we devalue people who carry bigger burdens, when really our response should be to carry one another’s burdens in love, each of us using the measure of strength we have been given. We carry each other’s burdens because this is part of who we were created to be – those who serve one another in love.

And we do this back and forth, for each other. Those who are healthy do what those who are sick cannot. Those who are sick care for their caretakers as well, proving a listening ear, showing interest in their life, looking out for their needs, and encouraging them to ask for help.

If you are considering suicide, know that the people around you would not be better off without you. Who you are is not measured by how much you are able to accomplish or do. From the moment you were born, you were filled with great value and great worth, given to you by God that can never be taken away, no matter how bad the pain becomes, no matter how long the pain persists.

If you are experiencing suicidal thoughts, please call The National Suicide Hotline at 1-800-273-8255. (USA only...hopefully there exists something similar in your own country Ed.)

Joiner, T. (2011) Myths About Suicide. Cambridge, MA: Harvard University Press

Tang N. K. Y. and Crane, C. (2006). Suicidality in chronic pain: A review of prevalence, risk factors, and psychological links. Psychological Medicine, 36(5), 575-586.

http://www.lifeinslowmotionblog.com/understanding-why-individuals-with-severe-pain-and-illness-die-by-suicide-and-what-we-can-do-about-it/

Nerve Cell Transplantation Study For Neuropathic Pain

Today's post from allvoices.com (see link below) reveals a little bit more information about the research into the transplantation of nerve cells to treat neuropathic pain. It's a complex subject so every new explanation of how it works will add to our understanding. It's clearly still a long way away from being successfully used on humans but the signs are good.

New study finds treatment for neuropathic pain
May 27th, 2012 by Sarah1

The neuropathic pain that results from damage to neurons was again studied by scientists recently. They experimented the transplantation of neurons to replace the damaged ones. The experiment involved transplanting immature neurons in mice. The immature neurons grew into full-nerve cells but not all of the those survived. However, it was proved that they can actually grow and function as complete cells.
"Now we are working toward the possibility of potential treatments that might eliminate the source of neuropathic pain, and that may be much more effective than drugs that aim only to treat symptomatically the pain that results from chronic, painful conditions," the senior author of the study, Allan Basbaum PhD, who is also the chair of the Department of Anatomy at UCSF, states in the study report, as reported on sciencedaily.com. The previous post here on the blog can be seen by clicking here.

Neuropathic pain is very difficult to treat, as even strong painkillers do not act on it. The study aimed at finding a way to treat the pain and the related diseases by replacing the lost nerve cells. The co-author of the study, Arnold Kriegstein, commented on the research, saying that he feels it is a starting point for further study. "This research is at a very early stage, and we're a long way from thinking about it in human trials, but we do have a method of making cells that are like these inhibitory neurons, starting with human embryonic stem cells," Kriegstein said in his remarks, as reported on sciencedaily.com.

The study suggests that transplantation of nerve cells would have a direct effect on the pain, something which is not achievable by medication. The advancement in the research can potentially lead to a conclusive treatment for humans, as the results of this experiment are very encouraging. "Unlike drugs, the transplanted cells can have very focused effects, depending on where they are transplanted," Kriegstein said about the new finding.

There might be various causes of the pain and the scientists are working on determining the specific causes that are treatable by this newly proposed therapy. They are hopeful that they would be successful in finding the cure through this method. The study has opened a new window for the treatment of neuropathic pain, which is usually considered untreatable.

sarah1 is based in California, California, United States of America, and is a Reporter for Allvoices.    

http://www.allvoices.com/contributed-news/12256335-study-conducted-to-find-treatment-for-chronic-pain      

Still Waiting For Firm Evidence That Marijuana Helps Pain

Today's post from newswise.com (see link below) throws a cautionary note into the arguments concerning marijuana as an analgesic. As the article points out, much of the evidence showing the benefits of cannabinoids for pain patients is anecdotal and asks for more studies to provide much more hard evidence. It certainly seems that marijuana can be extremely helpful to patients with chronic nerve pain; everything points that way and there are thousands of examples of satisfied patients struggling against outdated lawgivers etc etc but it is true that we need as much hard evidence as possible to remove all shadow of doubt and in our current systems, that can only come from extensive studies and research by recognised medical bodies. The only way that we can prevent people from being criminalised for treating their pain, is providing irrefutable evidence, so let's get on with gathering that evidence as quickly as possible.
 

Strong Evidence Still Lacking on Medical Marijuana for Pain
Some Case Studies Show Efficacy, More Scientific Studies Needed
Released: 15-May-2015

Source Newsroom: American Pain Society more news from this source
Contact Information Available for logged-in reporters only
Citations American Pain Society Annual Scientific Meeting

PNewswise — ALM SPRINGS, May 15, 2015 – With increasing numbers of chronic pain patients experimenting with marijuana to get relief, physicians need to learn more about the plant and its constituents to counsel patients appropriately about its safety and possible analgesic benefits, according to a leading medical marijuana researcher speaking today in a plenary session at the American Pain Society Annual Scientific Meeting, www.americanpainsociety.org.

Mark Ware, M.D., executive director, Canadian Consortium for the Investigation of Cannabinoids and director of clinical research, Alan Edwards Pain Management Unit, McGill University Health Center, moved to Canada in 1999 following a court decision that legalized marijuana there. He had been working in Jamaica at a sickle-cell anemia clinic, where he encountered several patients who told him that using marijuana eased their pain. At McGill University, Ware evaluates claims from patients about the medical benefits of marijuana and is involved in research on the long-term safety of the plant in patients using it for chronic conditions.

“Much of what we know about medical marijuana is anecdotal, so the challenge is to recognize that patients who say they get pain relief by self medicating with marijuana may be right, and move forward in conducting more scientific studies to better understand its analgesic benefits and overall safety,” said Ware.

The New York Times has reported that worldwide some 15 trials of medical cannabinoids have been conducted. Results have shown effectiveness in reducing pain from neuropathy, diabetes and fibromyalgia.

The FDA has approved two cannabinoid medications, dronabinal and nabilone. They are prescribed for controlling nausea and vomiting caused by chemotherapy and to treat anorexia in HIV patients. Other cannabinoid-based medications are under FDA review for treating cancer pain and other conditions.

Ware said several challenges lie ahead for conducting marijuana pain studies. “With legalization of medical marijuana in more than 20 states, widespread access will yield more reports that need to be evaluated,” said Ware. “And, while it’s clear that large, Phase 3 clinical trials are needed to better understand medical marijuana’s potential clinical efficacy, who will pay for them and is it necessary to conduct trials for every pain condition that could be treated with marijuana?”

Another obstacle for medical marijuana research, according to Ware, is lack of standardized products. “Plants grown in Colorado and other legalization states could be different, so when talking about cannabis in various states, there could be a variety of compounds,” he said. According to the National Institute on Drug Abuse, most marijuana used as medicine is the same quality and carries the same health risks as marijuana sold on the street.

New studies also are needed to explore safety problems. “There are safety concerns about the molecule itself, and studies of recreational marijuana users show the drug can affect the brain and lungs. Questions also arise about smoking as a safe route of administration vs. oral dosing,” Ware stated.

In states where medical marijuana is legal, physicians have discretion in advising patients about using it for pain management. “Doctors are being asked every day if using marijuana can lessen pain intensity,” said Ware. “Even though there are no efficacy and safety data from large controlled clinical trials, doctors interested in medical marijuana should learn about the plant itself and its myriad active ingredients by reviewing the scientific literature, understanding local legal issues and potential liability, and weighing the risks and benefits vs. other analgesics, including opioids.”

About the American Pain Society

Based in Chicago, the American Pain Society (APS) is a multidisciplinary community that brings together a diverse group of scientists, clinicians and other professionals to increase the knowledge of pain and transform public policy and clinical practice to reduce pain-related suffering. APS is the professional home for investigators involved in all aspects of pain research including basic, translational, clinical and health services research to obtain the support and inspiration they need to flourish professionally. APS strongly advocates expansion of high quality pain research to help advance science to achieve effective and responsible pain relief. For more information on APS, visit www.americanpainsociety.org. 

http://www.newswise.com/articles/strong-evidence-still-lacking-on-medical-marijuana-for-pain

Has Spinal Cord Stimulation Improved To The Point Where It Provides A Viable Alternative For Chronic Nerve Pain

Today's post from medlatest.com (see link below) reports on an interesting discussion about Spinal Cord Stimulation as being a means of reducing chronic nerve pain. Spinal Cord Stimulation has been around for years of course but has suffered from poor results and neuropathy patients and doctors alike have become reluctant to offer, or try it. In these days of looking for opioid alternatives, it's logical that SCS methods will be re-examined and that's exactly why these specialists got together to discuss the issue. It's somewhat ironic that research into treatments for neuropathy has been stagnant for decades but the minute that opioids become a 'hot' issue, then research into pain relief goes into overdrive. That said, nerve pain patients mustn't grumble: at least efforts are now being made to find alternative solutions. However, this discussion concluded that patient reluctance regarding SCS is based on past experiences with older technology which rarely worked as was hoped. The physicians maintain that the technology has now moved on to the point where success in controlling pain via electrical stimulation is now much more likely. The problem lies in how you measure pain and results and this is a whole new ball game because pain is so subjective and by asking a patient to point to a smiley face to indicate their pain levels, you might as well lick your finger and stick it in the air. The conclusion must be that if SCS technology is so much better, then evaluation methods need to drastically change to catch up. Interesting read.

The Case for Spinal Cord Stimulation in Chronic Pain
Source: Boston Scientific March 10, 2017 

Expert physicians gathered in a round table event to discuss Spinal Cord Stimulation as a treatment for chronic pain.

Background 

With opioid abuse posing a national health crisis, the American College of Physicians recently issued a new guideline to promote treatment alternatives like acupuncture and yoga ahead of opioids on the treatment continuum for low back pain. But, many pain specialists believe alternative therapies like these don’t provide adequate symptom relief, leaving patients to look toward opioids as their only option.

A group of the nation’s leading experts in spinal cord stimulation (SCS) convened for a roundtable discussion at the 2017 North American Neuromodulation Society Annual Meeting to discuss why SCS should be used earlier in the treatment continuum and how it can play a role in addressing the ongoing opioid epidemic.

What becomes immediately apparent on reading the executive summary from the discussion, is that all 6 participants shared the view that SCS should play a much greater role in the management of chronic pain. There was unanimity of opinion that opioid use is problematic, carrying risks of misuse and abuse, while also only being “50% effective in 30% of patients treated.”

Management of patients off their opiates is of course another problem for the clinician, withdrawal being a weaning process and requiring an educational approach. The consensus seemed to be that SCS should be positioned ahead of opiates in the pain treatment continuum.

So why isn’t that already the case? Well it seems that the early days of the therapy weren’t quite as successful as today, which may have spawned resistance in both the clinical and patient community. The panel took this subject on too, suggesting that older technologies presented difficulties targeting specific nerves, while today’s is considered “not the same therapy” and “capable of yielding 100% pain relief.”

The final topic was the SCS patient pathway, the group concluding that the subjective nature of current pain scoring methods meant that their use should not be the only factor. The group expressed a desire to work with medical societies and regulatory bodies to develop a more nuanced standard for measuring patient outcomes.

Selected Physician comments 

Dr. Mark Wallace, chair of the division of Pain Medicine in the Department of Anesthesiology of University of California at San Diego stated; “In my 25 years’ experience, all of my patients reduced their opiates once I put a spinal cord stimulator in them. Most of them completely go off of the opiates. So what we need to do is we need to position the neuromodulations before opiates, and we need to change the pain treatment continuum and get it earlier in the treatment continuum so we can keep patients from starting the opioids in the first place.”

On the subject of the modern SCS therapies, Dr Julie Pilitsis, professor of neurosurgery and of neuroscience at Albany Medical College and Chair of the Department of Neuroscience and Experimental Therapeutic, stated; “I would just like to encourage people…that may have had a negative experience with spinal cord stimulation 20 or 30 years ago to come back to the therapy. It is not the same therapy. We have so many more capabilities. We can help so many more people.”

On the need for a new approach to scoring patients for pain levels, Dr Simon Thomson, consultant in pain medicine and neuromodulation at Basildon and Thurrock University NHS Trust, UK, stated; “I think most people would say in something like chronic pain, it’s plainly ridiculous just to have linear pain scores to define, if you like, the suffering that this patient and those around them are going through … the measure that seems to best define what we’re looking at achieving in our patients is a health-related quality of life measure.”

http://www.medlatest.com/clinical-educational/congresses-meetings/case-spinal-cord-stimulation-chronic-pain/

Chronic Pain Reduced By Cannabis Receptors Without Cannabis Or Opioids!

Today's post from sciencedaily.com (see link below) could be an astonishing breakthrough in the battle against neuropathic pain. It discusses research on certain compounds that can modify the brain's cannabis receptors to reduce chronic pain symptoms, without the need for cannabis itself, or strong opioid-type drugs and most importantly, without any side effects! The science in the second half of the article may leave you somewhat baffled but the message in the first half is easy to understand. What's ironic is that the current hysteria about opioid addiction and overdose deaths has been the trigger for this research. This reflects the current state of medical research: if there's enough demand (the 'disease' becomes widespread or the group of patients grows enormously) suddenly money appears for research and development. Never underestimate the pharmaceutical industry's ability to sniff out profits!  That's not very encouraging for people with rare diseases or those who belong to a small group of patients but in our case, we have 20 million Americans with neuropathy and a media hype over opioid abuse and its consequences - a double stimulus to pour money into research. That's why we're suddenly seeing advances in research regarding nerve pain and its treatments, even if they are only tested on long-suffering rodents - it's about time!!

Compound suggests chronic pain treatment without opioid or medical marijuana side effects 
November 15, 2016 Source: Indiana University 

FULL STORY

Indiana University neuroscientist Andrea Hohmann took the stage at a press conference Nov. 14 in San Diego to discuss research conducted at IU that has found evidence that the brain's cannabis receptors may be used to treat chronic pain without the side effects associated with opioid-based pain relievers or medical marijuana.

The study was discussed during the annual meeting of the Society for Neuroscience, the world's largest source of emerging news about brain science and health. Hohmann was joined by three other international researchers whose work focuses on similar topics.

"The most exciting aspect of this research is the potential to produce the same therapeutic benefits as opioid-based pain relievers without side effects like addiction risk or increased tolerance over time," said Hohmann, a Linda and Jack Gill Chair of Neuroscience and professor in the IU Bloomington College of Arts and Sciences' Department of Psychological and Brain Sciences.

Chronic pain is estimated to affect nearly 50 million adults in the United States. The rise in opioid-based pain relievers to treat chronic pain has also contributed to an opioid addiction epidemic in the United States, with 19,000 deaths linked to prescription opioid abuse in 2014. In Indiana, the use of needles associated with prescription opioid abuse led to a major HIV outbreak in the state's southeastern region, prompting the governor to declare a public health emergency in 2015.

"The fact that deaths associated with prescription opioid abuse have surpassed cocaine and heroin overdose deaths combined is a significant factor in exploring cannabinoids as an alternative treatment for pain," said Richard Slivicki, a graduate student in Hohmann's lab who led the study. "It's a major epidemiological crisis, and one that helps motivate our work."

The IU study found that a compound that modulates the activity of the brain's receptors for THC and endocannabinoids reduced chronic pain in mice. THC, or tetrahydrocannabinol, is the main psychoactive ingredient in marijuana; endocannabinoids are natural pain-relieving compounds released by the brain.

These modulating compounds, called positive allosteric modulators, or PAMs, work by binding to a recently discovered site on a cannabinoid receptor in the brain called CB1, which is different from the site that binds THC. The PAMs were synthesized by Ganesh A. Thakur at Northeastern University, who is a collaborator on the study.

The IU scientists specifically tested the effects of CB1 PAM on neuropathic pain, a type of chronic pain caused by nerve damage, which is estimated to affect as many as 40 percent of cancer patients as a side effect of chemotherapy. The scientists gave mice paclitaxel, a chemotherapy drug known to damage nerves and cause pain, and then treated them with CB1 PAM.

After receiving paclitaxel, mice became hypersensitive to both mechanical and cold stimulations to the paw, indicating increased pain. After treatment with the CB1 PAM, the mice behaved like normal mice that did not experience pain.

The study also found evidence that the use of CB1 PAM amplified the therapeutic effect of endocannabinoids without the negative side effects of a "marijuana high," such as impaired motor function. The PAMs were administered in combination with a compound to increase endocannabinoid levels in the brain by preventing their breakdown in the body.

Moreover, the team found that the use of the CB1 PAM remained effective over time to prevent pain in mice, as opposed to THC and endocannabinoid breakdown inhibitors, both of which stopped working with repeated dosing.

"We found that the compound did not produce reward on its own, so it's unlikely that a CB1 PAM would be abused as a recreational drug," Hohmann added. "Our studies show that we can maintain or preserve therapeutic efficacy in ways that we haven't seen with some of the other classes of analgesics that are used in the clinic."

The event was titled "Targeting the Brain's Cannabinoid System."

Story Source:

Materials provided by Indiana University. Note: Content may be edited for style and length.

Cite This Page:
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Indiana University. "Compound suggests chronic pain treatment without opioid or medical marijuana side effects." ScienceDaily. ScienceDaily, 15 November 2016. .

RELATED TOPICS
Health & Medicine
Pain Control
Neuropathy
Controlled Substances
Mind & Brain
Opium
Marijuana
Brain Injury


RELATED TERMS
Opioid drug
Chronic pain
Aggression
Cannabis
Psychoactive drug
Anticonvulsant
 
https://www.sciencedaily.com/releases/2016/11/161115085503.htm

Pain in the Brain A Guide to Chronic Pain

Today's useful Australian animated video shows you precisely why the pain you have when afflicted by neuropathy (amongst other diseases), is called Chronic Pain. Always handy to know the basics!

"Brain Man" A collaborative video made by The Hunter Integrated Pain Service and GP Access

Dealing With Chronic Pain

Today's post from canadianliving.com (see link below) is an extract from a somewhat longer article about controlling pain which begins with a personal account which is not shown here. What you read here is relevant to people suffering from neuropathic pain and looks at holistic treatment and possible choices for self-help. There is of course more reference to the Canadian situation but everything here could be of value to anyone looking for answers when the drug treatments are not working as they should. Worth a read.

How to deal with chronic pain

By Anna Sharratt

Chronic pain sufferers are finding relief in holistic solutions that involve innovative mind-body approaches and new therapeutic techniques. It's a far cry from the days of popping painkillers and curling up with a hot pack.

.......

The consequence of chronic painThe root cause of chronic pain often remains a mystery. Another survey carried out last year, by Harris/Decima for Pfizer Canada, found that among those who have been regularly suffering from two or more symptoms of chronic pain for more than six months, almost half (47 per cent) have not been diagnosed.

Chronic pain is also costly, with nine per cent of women and 10 per cent of men with chronic pain reporting that their pain interferes with their ability to work. The price tag is an estimated $12,558 in lost income per person with pain per year, according to SES.

Worse, it can have devastating consequences on self-esteem. When Nicole St-Laurent-Ward, 53, of Moncton, N.B., developed fibromyalgia in 1995, the excruciating pain in her hips began to limit her mobility and led to chronic fatigue. She was forced to quit her job at Radio-Canada and became depressed and anxious. "I felt scattered, disconnected," she says.

Seeking help
Like Kelly, Nicole sought help from traditional pain drugs. But while over-the-counter pain relievers, such as hot packs and analgesic rubs, are readily available in drugstores, they're not likely to do the trick for chronic, unremitting pain. It's often a challenge for chronic pain sufferers to get effective prescription pain medication, partly because doctors are leery of taking on the task. "Are patients undertreated? I think so," says Dr. Zohar Waisman, a psychiatrist with the Wasser Pain Management Centre in Toronto. "Unlike an infection, where we give a person antibiotics," he says, "chronic pain is much more complicated to deal with."

That's not to say there isn't a wide variety of effective prescription pain relievers. First, there are the opioids, such as codeine, morphine, oxycodone and methadone, which can be critical in chronic pain management, says Mary Lynch, president-elect of the Canadian Pain Society and director of pain management at Queen Elizabeth II Health Sciences Centre in Halifax. These drugs, which are most often taken orally but can be infused (administered through intravenous, intraspinal, epidural or subcutaneous routes) or applied through the skin with a patch, can be important in managing pain. However, doctors need to screen for risk of addiction and watch for signs of overdose (recently reported with the use of fentanyl patches) and long-term dependence. "About 10 per cent of the population has the disease of addiction," says Allan Gordon, a neurologist and director at the Wasser Centre.

As well as the opioids, there are analgesic combinations – an antidepressant taken with an anticonvulsant – that act as aneuro-modulators, explains Lynch, meaning they alter the way the brain processes pain. Included in these combinations can be Gabapentin and Carbamazepine, anticonvulsant drugs formerly used solely to treat epileptic seizures.

Also emerging are the cannabinoids, drugs derived from cannabis, such as medical marijuana. "It's a field that is developing," says Lynch.

Accurate diagnosis
Before a doctor prescribes any of these drugs, though, he should make an accurate diagnosis. And that can be difficult because of the many different types of pain; for example, there are various forms of arthritis pain, neuropathic pain (stemming from an injury to the nervous system), multiple sclerosis pain, migraine pain and fibromyalgia, to name a few.

Accurately pinpointing the source of pain takes some detective work, but it's important because it can affect treatment, notes Marlene Noble, a physiotherapist at St. Paul's Hospital in Vancouver. "There's a whole different way of treating pain if it's peripheral pain due to a new injury than if it's long-term chronic pain," she says.The waiting gameUnfortunately, given an aging population that demands an increasing level of services, the waiting period for a thorough assessment and treatment plan can be long. Many pain clinics across the country have waiting lists of a year or longer.

But once patients do get assessed at a clinic, they're likely to be greeted with a whole new approach to treatment. They may be seen by a pain specialist and a psychiatrist, as well as a neurologist and a physiotherapist – all under one roof.

It's part of the new mind shift in chronic pain management that's been burgeoning over the last 10 years. The emphasis has changed from a quick fix to patients learning how to self-manage their pain for a lifetime, explains Noble. Today, there is also more of a team approach; members of a treatment team work together on all aspects of the pain problem, including psychological, social and physical. "You really have to look at all areas of that person and not just the pain problem," she says.

Alternative therapy

Acupuncture is an increasingly important part of this new holistic approach. A mainstay of Chinese medicine, acupuncture balances the body's energy by inserting fine sterile needles under the skin at specific points along energy pathways (meridians). When treating pain, the needles are sometimes placed on the opposite body part to that afflicted with pain (on a right hand, for example, if the left hand is affected), says David A. Bray, a doctor of traditional Chinese medicine in Toronto.

There's mounting evidence that acupuncture reduces pain, especially for people with muscular, nerve and lower-back pain. German researchers recently found that patients who were treated with acupuncture over six weeks experienced a nearly 50 per cent decrease in pain intensity, while those treated with conventional treatments over the same period had a less than 25 per cent decrease in pain.

A growing body of research is uncovering the benefits of other alternative approaches to pain, too. For example, a study released last September found that tai chi, qi gong and yoga in particular improved arthritis pain, joint pain and stiffness; and in other studies, yoga improved hip extension and stride length, and reduced joint tenderness and hand pain.

As well as traditional drugs, Nicole uses the holistic approach, including massage, reflexology and meditation, to keep her pain manageable. "I think it was a wake-up call for my health," she says.

As for Kelly, both meditation and acupuncture helped reduce her pain. Recent personal issues made it difficult for her to continue these practices, but she says she wants to get back to them. "I'm open to anything that works."

Embracing the holistic approachAs the pain management community embraces a holistic approach to care, it's also beginning to view pain itself in a whole new light. Increasingly, pain is seen less as a physical affliction and more as the result of an injury that permanently changes the brain and leaves a lingering fear. "When someone hurts you as a kid, you remember it really well," explains Min Zhou, a pain researcher at the University of Toronto. "The idea is that the injury leaves a mark that doesn't go away, which can trigger pain long after the initial symptoms have subsided." Zhou's research focuses on the part of the brain that may be responsible for that – the anterior cingulate cortex, located in the prefrontal cortex. It's an area that "lights up" in diagnostic tests, such as a functional MRI, when a person is exposed to painful stimuli.

Zhou has developed a genetically mutant mouse that feels pain such as a needle prick, but not chronic pain. He's optimistic that this model will lead the way to the development of a drug that reduces chronic pain but preserves other sensations like hot and cold in humans – something that current pain medicines can't do. (Many patients who take drugs like oxycodone lose sensation of hot and cold.) But Zhou acknowledges that such a drug could take at least 10 years to develop.

Kelly certainly hopes that day will come a lot sooner. Dosed up on oxycodone and still suffering from chronic inflammation, she says even short trips to Tim Hortons can be gruelling and are a regular reminder of her reduced quality of life. But she's determined nonetheless. "You've got to keep going," she says.

Managing
Dealing with long-term pain can be exhausting and emotionally draining. Here are some tips for coping.
• Chronicle the pain. Day-to-day tracking of pain and paying attention to the variations in intensity can provide clues as to the nature and severity of the condition, while providing a scale on which to grade the pain, says David A. Bray, a doctor of Chinese medicine in Toronto.

• Get a referral to a pain clinic. Such a referral may be key since some family doctors don't feel comfortable managing chronic pain, says Dr. Zohar Waisman, a neurologist in Toronto. Beware: You may have a long wait ahead of you.

• Learn the stages of pain. By doing so, you'll understand the different treatment approaches, including the physical and cognitive techniques such as meditation, says Marlene Noble, a physiotherapist in Vancouver.
• Keep moving. With help from a pain clinic specialist or doctor, develop an exercise routine, such as yoga, that keeps you limber. The worst thing patients can do is not exercise, says Noble.

• Be your own pain advocate. "You can't just sit back and let the doctors do it," says Kelly Corry, a chronic pain sufferer In Hillsdale, Ont. What you can do: search out pain specialists on the Internet, join a support group to share findings, know your treatment options and be vocal about your concerns to doctors, employers, friends and family.

http://www.canadianliving.com/health/prevention/how_to_deal_with_chronic_pain_5.php

Neuropathic Pain

Today's post from geenabhud.wordpress.com (see link below) has no visible original author and doesn't refer back to the original source but nevertheless, contains some very useful information for those wondering how neuropathic pain works and why it feels the way it does. It also refers to several verifiable scientific studies and is clearly informative and not opinion-based. Having checked through the article, the information is verifiable on countless other sites and working on the principle that neuropathy patients deserve to read all available information and from many different angles, this post is worth a read.

 

Treatment of Painful Peripheral Neuropathies
footpadpatch: November 6, 2012

INTRODUCTION

Peripheral neuropathy is a common problem and for some patients, pain is a disabling component of the neuropathy. The first goal in evaluating patients with painful peripheral neuropathies is to identify the cause, with the hope of identifying treatment to reverse nerve damage. There are a large number of disorders that may be associated with a painful peripheral neuropathy. (Table 1) When neuropathic pain is present, it is appropriate to treat this concurrently, during the evaluation, as well as during the treatment of the neuropathy, if identified is in process. For some types of neuropathy, there are no available treatments for the underlying disorder, and therapy for neuropathic pain, if present may be the only treatment available.

Pain can be classified broadly as two types. Nociceptive pain is protective and is a normal response to tissue injury, serving to warn of the presence of injury. There is also sensitization of peripheral nociceptors and central nervous system changes, which protect the damaged area by avoiding contact.

Neuropathic pain is a pathologic or maladaptive pain, which results from damage to the nervous system, producing pain in the absence of stimulation of nociceptors or inappropriate response to stimulation of nociceptors. Nociceptive and neuropathic pain are not synonymous with acute and chronic pain. For instance, rheumatoid arthritis is a chronic pain, which is nociceptive pain. A herniated disc can cause acute sciatic pain, which is neuropathic.

Patients with neuropathic pain typically describe burning, lancinating, stabbing, cramping, aching and sometimes vice-like pain. It can be paroxysmal or constant. On examination hyperalgesia, allodynia or hyperpathia are sometimes elicited.

The normal pathways involved in the transmission of pain begin with stimulation of nociceptors including those that respond to chemical irritant stimuli such as VR1, DRASIC, P2X3 and noxious heat stimuli such as VR1 and VRL1. Signals resulting from intense mechanical and thermal stimulate A delta fiber nociceptors and intense mechanical ,thermal and chemical stimuli stimulate polymodal C nociceptors. Afferent fibers synapse in Rexed’s lamina I, II and V in the spinal cord, which is the first level of modulation. Opiate receptors and interneurons are present at the dorsal horn. There are are also descending inputs from the hypothalamus, periaqueductal gray. Opiods, norepineprhine and serotonin have modulatory effects on pain transmission.

MECHANISMS OF NEUROPATHIC PAIN
Why certain neuropathies cause pain is unknown, but there has been increasing knowledge about the mechanism of pain. The gate theory of pain proposed that the substantia gelatinosa acted as a gate allowing pain transmission to proceed and that the inhibitory affect of the substantia gelatinosa is increased by large diameter fibers. Central descending influence was also postulated. [Melzack and Wall 1965]Though specifics of this theory have been shown to be incorrect, the basic premise of central modification of pain perception at the dorsal horn and other parts of the central nervous system is still held. Dyck et al [Dyck et al. 1976], noted that neuropathic pain was related to the rate and kind of nerve fiber degeneration. It is not related simply to the ratio of remaining large and small nerve fibers. Brown et al noted that unmyelinated and small myelinated fibers were most prominently involved and unmyelinated nerve fiber sprouting was evident in painful diabetic neuropathy. [Brown et al. 1976]

Animal models of pain have added to the understanding of neuropathic pain. There are 4 commonly used animal models, which include the chronic constrictive injury (CCI) model, the partial nerve transection, spinal nerve transection model and the spared nerve model. [Kim and Chung 1992;Seltzer et al. 1990;Bennett and Xie 1988;Decosterd and Woolf 2000]The chronic constrictive injury model is produced by a loosely constrictive ligature around the sciatic nerve. [Bennett and Xie1988] Almost all of A-β fibers die, as do the majority of Aδ fibers. A large percentage of C fibers persist.

The partial nerve transection model involves tightly ligating and transecting 1/3 to ½ of of the rat sciatic nerve. The spinal nerve transection model involves tight ligation and transection of the L5 and L6 nerve roots. This affects 50% of the sural and saphenous nerve fibers. The spared nerve model involves a lesion of 2 of the 3 terminal branches of the sciatic nerve (tibial and peroneal) intact, leaving the sural nerve intact. [Decosterd and Woolf2000]There is partial deafferentation but not differential involvement of nerve fibers, in these three models.

Heat hyperalgesia, mechano-hyperalgesia, mechano-allodynia and cold-allodynia may be observed and behavioral changes consistent with spontaneous pain such as limping and guarding the hind paw are seen. Both peripheral and central mechanisms have been observed in animal models.

After nerve injury there are spontaneous discharges of nerve fibers, neuromas and dorsal root ganglion. This has been seen in traumatic nerve injury models , as well as models of peripheral neuropathy from diabetes and heavy metal intoxication. Increased expression of sodium channels are seen in neuroma’s in humans and animal models. The density of sodium channel expression correlates with the degree of pain. [England et al. 1996] Changes in sodium channel expression are seen and may contribute to nerve excitability and spontaneous pain. [Waxman et al. 1999;Craner MJ et al. 2002].

These spontaneous discharges by themselves can cause pain, but they also have additional affects. C fiber afferents trigger cell death of neurons in the dorsal horn, where inhibitory interneurons are concentrated, possibly through an excitotoxic mechanism. This may result in increased pain transmission.. ([Sugimoto et al. 1989;Sugimoto et al. 1990;Laird and Bennett 1992] C fiber afferents release glutamate and synapse on 2nd order neurons and have excitatory affects. Glutamate synapses at AMPA receptors which depolarizes the membrane. This depolarization releases the inhibition of the NMDA receptor by the magnesium ions and there is an influx of calcium. Second order neurons are gradually depolarized and responses are amplified and this changes the response of neurons to subsequent input.

Two processes that are distinct occur at the dorsal horn which are designated “windup” and “central sensitization.” Windup up results from repetitive C fiber firing at low frequencies that result in a progressive buildup of the amplitude of the response of the dorsal horn neuron, only during the repetitive train. Central sensitization is an abnormal sensitivity with a spread of hypersensitivity to uninjured sites and pain resulting from stimulation of low threshold A mechanoreceptors. Central sensitization follows a brief high frequency input and the increased response to subsequent inputs is prolonged. Both can be blocked by NMDA receptor antagonists. Central sensitization can result from windup. This is a result of the calcium influx through the NMDA receptor following depolarization of the dorsal horn membrane. The intracellular calcium activated a number of kinases of which protein kinase C (PKC) is likely important. PKC enhances the NMDA receptor , which results in subsequent glutamate binding of the NMDA receptor generating an inward current. Though windup can result in central sensitization it is not necessary for central sensitization to occur. [Woolf and Salter 2000;Woolf 1996]

Similar observations had previously been noted by Denny-Brown who described an enlarged and hypersensitive dermatomal region in primates when severing the surrounding nerve roots distal to the dorsal root ganglion compared with severing proximal to the DRG. This suggested plasticity of the dorsal horn neurons secondary to input from the DRG. [Kirk and Denny-Brown 1970;Kirk and Denny-Brown1970;Denny-Brown et al. 1973]

Nerve injury also results in sprouting of myelinated fibers into lamina II of the dorsal horn, which under normal circumstances receives only C fiber input. [Mannion et al. 1996]This may result in allodynia.

There is a genetic influence on the experience of neuropathic pain though it is poorly delineated. There are variations on the expression of pain behaviors seen in different strains of animals. [Devor and Raber 1990] A recent study noted that 56% of patients with painful diabetic neuropathy had a relative with painful diabetic neuropathy suggesting a genetic component.[Galer et al. 2000]

The relative importance of these various mechanisms is not clearly known, however there is potentially multiple sites for intervention in treating painful neuropathies.

Medications
Tricyclic anti-depressants have been beneficial in controlled studies of neuropathic pain. [Max 1995]They block the reuptake of norepinephrine and serotonin and are thought to modulate descending inhibitory pathways. There benefit with neuropathic pain is independent of their effect on depression. [Max et al. 1987] Patients who are not depressed can respond and lower doses than are used to treat depression are effective to treat neuropathic pain. Tricyclic anti-depressants can block voltage dependent sodium channels and this may contribute to their efficacy to treat neuropathic pain. [Brau et al. 2001] They are typically started at a dose of 10-25 mg at night and titrated as tolerated up to a dose of 150 mg if necessary. Side effects include dry mouth, cardiac arrhythmias, urinary retention and sexual dysfunction. Venlafaxine has fewer side effects and has also been reported to benefit neuropathy pain. [Ansari 2000]

The selective serotinin reuptake inhibitors (SSRI) have been less effective for treatment of neuropathic pain. Fluoxetine was not effective in clinical trials. [Max et al. 1992]Paroxetine and Citalopram been reported to be effective. [Sindrup et al. 1992;Sindrup et al. 1990]

Anticonvulsants have also been studied in neuropathic pain. Both phenytoin (Dilantin) and carbamezapine (Tegretol) have been beneficial in trials of diabetic neuropathy. [Chadda VS 1978;Rull et al. 1969]They act as sodium channel blockers. Both medications have frequent side effects that are well known.

Gapapentin (Neurontin), binding site alpha delta Ca channel. It is though to act at a spinal site of action. [Xiao and Bennett 1996] Controlled studies in diabetic neuropathy, post-herpetic neuralgia and other neuropathic pain states. [Backonja et al. 1998] Starting doses are usually100mg tid or 300mg qhs. Unless the drug is not tolerated or a dose of 600 mg tid has been tried it should not be considered a treatment failure. Often higher doses provide more benefit. Side effects include drowsiness, fogginess, leg edema. Gabapentin is cleared by the kidneys and there are not significant drug interactions. The dosing should be adjusted in renal insufficiency and failure.

Lamotrigine (Lamictal) is a sodium channel blocker, which also inhibits glutamate release. It has reduced cold allodynia in the CCI model. [Hunter et al. 1997]Lamotrigine is effective in controlled studies in diabetic, HIV associated painful neuropathy, post-herpetic neuralgia, and trigeminal neuralgia.[Simpson et al. 2000;Eisenberg et al. 2001]. I’ve found lamotrigine to cause less drowsiness or dizziness than most other medications used for neuropathic pain and though these symptoms have been seen during epilepsy trials, they were not seen more commonly than placebo in 2 recent trials of neuropathy pain. Rash is a side effect and a Stevens Johnson syndrome may occur. This is less frequent when the medication is titrated slowly. The rash is less common with a slow titration. The following titration schedule has been used for neuropathic pain: 25mg qd for 2 weeks, 25 mg bid for the next 2 weeks, 50 mg bid for the next 2 weeks, 100mg bid for 2 weeks. If the patient is also taking valproate which inhibits the metabolism of lamotrigine, a dose of 25 mg qod is recommended as an initial dose.

Oxcarbazepine (Trileptal) is similar in structure to carbamezapine, but lacks the 10,11 epoxide, which is thought to be responsible for better tolerability. Autoinduction does not occur and rash and drug interactions are less frequent than with carbamezapine. Hyponatremia does occur. [Zakrzewska and Patsalos 1989]

Double blind placebo controlled studies of mexilitine have been negative, however subgroups with stabbing and burning pain had benefit. Another study noted benefit in night time pain with the 675 mg dose, but not the lower doses of 450 mg or 225 mg.

Topiramate (Topamax) showed benefit in animal models and preliminary studies and anecdotal reports of diabetic neuropathy and neuropathic pain. [Edwards et al. 2000;Potter and Edwards 1998]Though the results have not been published Johnson & Johnson announced that the results of clinical trials in diabetic neuropathy pain were not positive (Reuter 9/18/2001).

Dextromorthorphan is a low affinity NMDA antigonist. It has been beneficial in animal studies and painful neuropathies. Side effects are frequent and it is poorly tolerated. [Nelson et al. 1997] Dextromethorphan in combination with other medications as well as more selective NMDA receptor antagonists that may have less side effects are being pursued.[Boyce et al. 1999]

Clonidine an alpha-2 agonist, as a transdermal patch was successfully used in a subset of patients with painful diabetic neuropathy using an enrolled enrichment design. Tizanidine, also an alpha-2 agonist, reduces thermal hyperalgesia in the CCI rat model and has been successful in open label studies in neuropathic pain.[Hord et al. 2001;Semenchuk and Sherman 2000b]

Tramodol (Ultram) has been effective in studies of painful diabetic neuropathy.[Harati et al. 1998] Side effects include nausea, headache, constipation, somnolence and seizures. Lidoderm is beneficial for post-herpetic neuralgia. The dose of 1-3 patches for 12 hours, with 12 hours off the patch. It has been beneficial in other forms of neuropathic pain. [Devers and Galer 2000]

Based on small preliminary and anecdotal series, as well as animal data, other medications including zonisamide and levetiracetam may be beneficial. [Backonja 2002;Semenchuk and Sherman 2000a;Hord et al2001]

HIV painful neuropathy is a particularly difficult syndrome to treat. Controlled studies of amitriptyline, mexilitine, and acupuncture have been negative. [Shlay et al. 1998;Kieburtz et al. 1998]Gabapentin has been reported to be successful, though requiring higher doses. [Newshan 1998] Phenytoin and carbamezapine as P450 inducers should be avoided as they can induce the metabolism of the protease inhibitors and make them ineffective. [Romanelli et al. 2000]Lamotrigine has been successful in blinded placebo controlled studies. Two consecutive studies however provided conflicting data with the first suggesting that there was no benefit above placebo in patients taking neurotoxic dideoxynucleotide anti-retrovirals compared with those patient not taking neurotoxic antiretrovirals and the second study showed the opposite. [Simpson et al. 2002;Simpson et al2000]

Since several different mechanisms are involved in neuropathic pain, treatment directed against the mechanism of pain would be desirable and has been proposed. Unequivocally identifying mechanisms at work to date has been difficult in patients. For instance the symptom of allodynia may occur from peripheral sensitization or central sensitization. [Woolf et al. 1998] It is a commonly held belief that tricyclic anti-depressants are more effective against burning pain and anti-convulsants are more effective against paroxysmal stabbing pain. In clinical trials however this has not been demonstrated.. Selective affects in animal models have been demonstrated. For example dextrorphan reduces heat hyperalgesia, but has no effect on mechanical allodynia in the CCI model. [Tal and Bennett 1994] How this correlates to treatment of people with neuropathic pain is still evolving. In the future cocktails targeting different mechanisms at work in patients with peripheral neuropathies may be possible.

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