The next study may be of little use to most of those suffering from TN, however, it has application to surgeries which pose a risk of TN or other neuropathic pain disorders. In 2007, Guindon, Desroches, Dani and Beaulieu at the Université de Montréal-CHUM reported that the suppression of neuropathic allodynia and hyperalgesia by WIN described previously was significantly enhanced by a one week pretreatment with WIN prior to the neural injury. This suggests that preemptively treating patients with cannabinoids prior to surgery with a high risk of inducing future neuralgia could significantly improve their chances of living a relatively pain-free life in the future (8).
CB1 vs CB2 vs CB1 and CB2
The studies discussed so far have all come to a conclusion that either the CB1 receptor alone (4,6,7) or a combination of both the CB1 and the CB2 receptors (5,8) are responsible for the antineuralgia effects of cannabinoids like WIN. There is however a growing body of evidence to suggest that CB2 receptor activation alone might be enough to produce cannabinoid mediated antineuralgia effects. A new CB2 receptor agonist was found to effectively reduce pain in rat models of neuropathic pain and three other types of pain without significantly effecting motor skills (9). Interestingly, unlike with the CB1 receptor, there is evidence from a mouse model of allodynia that only activation of CB2 receptors in the CNS, but not the periphery, is involved in the anti-allodynia produced by CB2 agonists (10). Yet another study has shown that neither CB1 nor CB2 receptors need be involved in cannabinoid mediated antihyperalgesia, but that cannabinoid mediated activation of vanilloid receptors (TRPV1) was enough (11). This study further suggested that the other terpenes and flavinoids in cannabis may work to potentiate the antinociceptive effect of the primary cannabinoids. Although targeting just CB2 or TRPV1 receptors may be a viable treatment for neuropathic pain, it is beginning to look more and more likely that pan-receptor cannabinoids like THC and WIN will provide the most benefit to the widest number of sufferers of neuropathic pain (12). This leads us to our next question: what role does the endocannabinoid system appear to play in the expression of—or reaction to—neuralgia?
Evidence from the Endocannabinoid System Itself
In 2006, Mitrirattanakul, et al., used the same rat model of neuropathic pain utilized in the majority of studies discussed above to help answer this question. They found that 76 to 83 per cent of the nociceptive neurons near the site of nerve damage expressed CB1 and TRPV1 receptors. After nerve damage, the density of nociceptive neurons expressing CB1 and TRPV1 receptors appeared unchanged whereas both the expression of RNA encoding for the CB1 protein in these cells and the protein itself were elevated, when compared to pre-damage levels. In some of these cells, TRPV1 expression and levels of endocannabinoids anandamide and 2-AG were also elevated (13). Increases in CB1 and CB2 receptor densities have also been observed in both the affected peripheral site and the CNS in a mouse model of neuralgia bearing greater resemblance to TN than the nerve damaged model of neuralgia used in most studies on rats. This study also verified that WIN was able to inhibit neuropathic allodynia and hyperalgesia (14). These findings suggest that the endocannabinoid system is upregulated in effected parts of the nervous system after neuropathic assault. This intern suggests that further manipulating the function of the endocannabinoid system may present a valuable target for future treatments for neuralgia.