Cannabinoid CB1 receptor upregulation in a rat model of chronic neuropathic pain

3-[2-Cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butanesulfonate (BAY 59-3074): A Novel Cannabinoid CB1/CB2Receptor Partial Agonist with Antihyperalgesic and Antiallodynic Effects

“…Alternatively, it could imply that the endocannabinoid system becomes more sensitive to the analgesic effects of cannabinoids in chronic pain conditions. As discussed by Richardson et al (1998), Drew et al (2000), Piomelli et al (2000), and Siegling et al (2001), possible mechanisms for such increased sensitivity include 1) increased expression of cannabinoid CB 1 and/or CB 2 (-like) receptors, 2) changes in cannabinoid CB 1 and/or CB 2 (-like) receptor function and/or G-protein coupling, 3) altered formation/release of endocannabinoids such as anandamide and 2-arachidonylglycerol, or 4) synergism with other endogenous ligands that are active only during chronic pain conditions.…”

“…Interestingly, the antihyperalgesic and antiallodynic effects of cannabinoids were typically obtained at doses that are generally lower than the doses needed to induce analgesic effects against acute, nonpathological pain (De Vry et al, 2004a). Although the mechanism underlying this increased potency of cannabinoids against chronic, pathological pain is not entirely clear, it was found that neuropathic pain coincided with an up-regulation of cannabinoid CB 1 receptor mRNA in the thalamus (Siegling et al, 2001). Because this up-regulation was observed in the contralateral but not ipsalateral thalamus compared with the unilateral nerve damage, it was suggested that the increased sensitivity of the endocannabinoid system is specifically related to the modulation of pain processing.…”

Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

“…59 Several receptors have analgesic effects in models of neuropathic pain. Upregulation of thalamic nicotinic and cannabinoid receptors has been reported after peripheral nerve injury models of neuropathic pain, [60][61][62] suggesting that supra-spinal nicotinic and cannabinoid receptors in the thalamus may contribute to the modulation of neuropathic pain responses. On the other hand, μ-opioid receptormediated G-protein activity was reduced in the thalamus of CCI mice, indicating an apparent desensitization in receptors from this region.…”

The Highs and Lows of Cannabinoid Receptor Expression in Disease: Mechanisms and Their Therapeutic Implications

“…Endocannabinoids are synthesized "on demand" from membrane phospholipids in response to increases in intracellular calcium (as occurs with neuronal activation or cell stress) and immediately released to act in paracrine fashion on nearby G i/o -protein coupled receptors CB 1 R 1 and CB 2 R. Endocannabi- Neuropathic pain CB 1 R and CB 2 R up-regulated in peripheral and central sensory pathways in animal models of neuropathic pain (Siegling et al, 2001;Lim et al, 2003;Zhang et al, 2003;Walczak et al, 2005;Mitrirattanakul et al, 2006).…”