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."

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

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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

MRI Scan Can Prove Whether Chronic Pain Drugs Work Or Not

Today's post from sciencedaily.com (see link below) looks at the possibility of using an MRI scan to measure the effectiveness of new drugs meant to reduce chronic pain. The MRI measures the nerve cells in the brain's response to pain signals and can see very quickly if they respond positively. Apparently one of the problems with new drugs is that it takes so long to prove effectiveness or not. By using a non-invasive MRI scan, gathering that evidence (from the behaviour of the brain's neurological response,) will be both quicker and more accurate, thus reducing the amount of time patients have to wait for proven new drugs for chronic pain.

Functional MRI may help identify new, effective painkillers for chronic pain sufferers 
Date:February 4, 2016 Source:American Society of Anesthesiologists

New research may allow new, more effective and safer pain medications to reach patients who suffer from chronic pain sooner. According to a recent study published in Anesthesiology, the official medical journal of the American Society of Anesthesiologists (ASA), using functional magnetic resonance imaging (FMRI), to measure the brain's neural response to pain, may be a viable tool for evaluating the effectiveness of new pain medications during the early stages of human drug development -- providing the needed objective evidence to prevent the premature discarding of potentially beneficial therapies.

"Many potential pain relieving drugs identified in preclinical research fail to reach the market because of a lack of early objective evidence that shows whether a drug is effectively reaching target pain receptors in the body and regulating chronic pain mechanisms," said Vishvarani Wanigasekera, M.D., study lead author and clinical post-doctoral research fellow, Nuffield Division of Anaesthetics, University of Oxford, England. "We have used noninvasive FMRI to successfully obtain such evidence that we hope can help to prevent the premature discarding of potentially effective pain relievers, as well as avoid exposing patients to ineffective ones."

Currently, patient reported pain relief is the primary outcome measure used in human drug development studies to assess whether a pain relieving medication is effective. However, due to their subjective and context-dependent nature, self-reported pain perception and relief is subject to many influences, in addition to the actual pain relieving effectiveness of the drug. Early drug development studies typically involve a small sample size. When subjective pain reports are used as the sole outcome measure in these studies, researchers can easily miss effective compounds that might work well in the population at large.

In the double-blind, randomized study, researchers induced a phenomenon called central sensitization and some symptom-like features of neuropathic pain, a complex chronic pain condition, on three separate occasions in 24 healthy volunteers by applying capsaicin cream, a topical irritant often used to produce similar characteristics of neuropathic pain in an experimental setting, on the subjects' skin. Prior to capsaicin cream application, subjects either received a single dose of gabapentin, which is considered effective and a first line treatment for neuropathic pain; ibuprofen, which is generally not considered an effective treatment for the condition; or a placebo. Researchers then assessed the effect the drugs or placebo had on the brain's neural response to pain using FMRI in addition to patient reported pain relief.

They found in the absence of behavioral measures distinguishing which drug was most effective at low subject numbers, the imaging responses were clear. Pain relevant neural activity was significantly reduced in the subjects who received gabapentin, even with extremely low subject numbers, highlighting the potential for FMRI to make a drug's effect clear in small cohorts.

The authors acknowledge that the mechanisms and neural activity involved in the expression of pain in neuropathic patients is not exactly the same as in the healthy subjects with capsaicin cream-induced pain. However, similar studies in early human drug development can determine whether a drug has the ability to affect relevant neural activity in the brain.

"There is a clear need for more effective, safer pain relievers," said Dr. Wanigasekera. "Chronic pain is a very common condition. Even the most effective pain medications currently available only provide adequate pain relief, defined as a 50 percent reduction in pain, in one out of four patients, while some drugs, such as opioids, have significant side effects, including dependence and overuse. We believe that neuroimaging techniques, such as FMRI, can provide objective evidence that can be used as outcome measures in early drug development to enhance the efficiency of the drug development process."

Story Source:

The above post is reprinted from materials provided by American Society of Anesthesiologists. Note: Materials may be edited for content and length.

Journal Reference:
Vishvarani Wanigasekera, Melvin Mezue, Jesper Andersson, Yazhuo Kong, Irene Tracey. Disambiguating Pharmacodynamic Efficacy from Behavior with Neuroimaging. Anesthesiology, 2016; 124 (1): 159 DOI: 10.1097/ALN.0000000000000924

http://www.sciencedaily.com/releases/2016/02/160204121949.htm