Endocannabinoid mechanisms of pain modulation

Abstract

Cannabinoids are antinociceptive in animal models of acute, tissue injury -, and nerve injury -induced nociception. This review examines the biology of endogenous cannabinoids (endocannabinoids) and behavioral, neurophysiological, and neuroanatomical evidence supporting the notion that cannabinoids play a role in pain modulation. Behavioral pharmacological approaches, in conjunction with the identifi cation and quantifi cation of endocannabinoids through the use of liquid and gas chromatography mass spectrometry, have provided insight into the functional roles of en docannabinoids in pain modulation. Here we examine the distribution of cannabinoid receptors and endocannabinoid-hydrolyzing enzymes within pain modulatory circuits to gether with behavioral, neurochemical, and neurophysiological studies that suggest a role for endocannabinoid signaling in pain modulation. This review will provide a comprehensive evaluation of the roles of the endocannabinoids 2-arachidonoylglycerol and anandamide in stress-induced analgesia. These fi ndings provide a functional framework with which to understand the roles of endocannabinoids in nociceptive processing at the supraspinal level.K EYWORDS: 2-arachidonoylglycerol , anandamide , CB1 , fatty acid amide hydrolase , monoacylglycerol lipase , periaqueductal gray , rostral ventromedial medulla

Hemopressin is an inverse agonist of CB 1 cannabinoid receptors

“…Because a large body of evidence has clearly demonstrated the antinociceptive action of CB 1 receptor agonists, these results are paradoxical (in that receptor antagonists also have antinociceptive effects; reviewed in refs. [23][24][25][26]. A possible explanation for these paradoxical in vivo effects (by CB 1 agonists and antagonists) could be that endocannabinoids activate distinct signal transduction pathways under different paradigms used to measure pain leading to distinct and opposing effects.…”

Peripheral antinociceptive effect of anandamide and drugs that affect the endocannabinoid system on the formalin test in normal and streptozotocin-diabetic rats

“…As current analgesic treatments for diabetic neuropathy are often considered ineffective and cannabinoids have been pointed out as emerging analgesic therapeutics (Lever and Rice, 2007), there is a growing interest in using these compounds for relieving neuropathic pain (Hohmann and Suplita, 2006), including neuropathic pain associated with diabetes. Previous studies have already demonstrated that local administration of a cannabinoid agonist WIN 55,212-2 is able to reduce mechanical allodynia in diabetic rats, suggesting local administration of cannabinoids as option for treatment of neuropathic pain in diabetic subjects (Ulugol et al, 2004).…”

Dynamic changes to the endocannabinoid system in models of chronic pain

“…Endocannabinoids also possess anti-nociceptive properties, and these have been thoroughly explored in animal models of pain (see references in recent studies [17][18][19]). Many chronic pain states have unknown aetiology and their underlying mechanisms remain unclear.…”