“Understanding how the body regulates pain is fundamental to develop rational strategies to combat the growing prevalence of chronic pain states, opioid dependency, and the increased financial burden to the medical care system.
Pain is the most prominent reason why Americans seek medical attention and extensive literature has identified the importance of the endocannabinoid pathway in controlling pain. Modulation of the endocannabinoid system offers new therapeutic opportunities for the selective control of excessive neuronal activity in several pain conditions (acute, inflammatory, chronic, and neuropathic).
Cannabinoids have a long history of medicinal use and their analgesic properties are well documented; however, there are major impediments to understanding cannabinoid pain modulation.
One major issue is the presence of psychotropic side effects associated with D9-tetrahydrocannabinol (THC) or synthetic derivatives, which puts an emphatic brake on their use. This dose-limiting effect prevents the appropriate degree of analgesia .
Animal studies have shown that the psychotropic effects are mediated via brain cannabinoid type 1 (CB1) receptors, while analgesic activity in chronic pain states may be mediated via CB1R action in the spinal cord, brainstem, peripheral sensory neurons, or immune cells.
The development of appropriate therapies is incumbent on our understanding of the role of peripheral versus central endocannabinoid-driven analgesia. Recent physiological, pharmacological, and anatomical studies provide evidence that one of the main roles of the endocannabinoid system is the regulation of gamma-aminobutyric acid (GABA) and/or glutamate release.
This article will review this evidence in the context of its implications for pain. We first provide a brief overview of CB1R’s role in the regulation of nociception, followed by a review of the evidence that the peripheral endocannabinoid system modulates nociception.
We then look in detail at regulation of central-mediated analgesia, followed up with evidence that cannabinoid mediated modulation of pain involves modulation of GABAergic and glutamatergic neurotransmission in key brain regions. Finally, we discuss cannabinoid action on non-neuronal cells in the context of inflammation and direct modulation of neurons.
This work stands to reveal long-standing controversies in the cannabinoid analgesia area that have had an impact on failed clinical trials and implementation of therapeutics targeting this system.”
https://www.ncbi.nlm.nih.gov/pubmed/31596190
https://www.tandfonline.com/doi/abs/10.1080/15504263.2019.1668100?journalCode=wjdd20
“Many Americans rely on opioids at varying dosages to help ameliorate their suffering. However, empirical evidence is mounting that opioids are ineffective at controlling non-cancer related chronic pain, and many argue the strategies meant to relieve patient suffering are contributing to the growing opioid epidemic.
“It is thought that endogenous cannabinoids have a role in the analgesia induced by specific forms of stress.
“Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics.
