Inhibition of fatty-acid amide hydrolase enhances cannabinoid stress-induced analgesia: Sites of action in the dorsolateral periaqueductal gray and rostral ventromedial medulla

A role for the ventral hippocampal endocannabinoid system in fear-conditioned analgesia and fear responding in the presence of nociceptive tone in rats

“…These findings corroborate the work of Hohmann and colleagues who have demonstrated involvement of the endocannabinoid system in a form of unconditioned stress-induced analgesia in rats [34]. Stress-induced analgesia is thought to be mediated by activation of the descending inhibitory pain pathway, of which the amygdala, PAG and RVM are key components, and indeed a key role for the endocannabinoid system in these brain regions during expression of stress-induced analgesia [16,34,74] and FCA [60,69] has been demonstrated. However, surprisingly, given its key role in contextual memory and limbic system function, there is a paucity of studies investigating the role of the vHip in stress-or fear-induced analgesia.…”

Cross-sensitization and cross-tolerance between exogenous cannabinoid antinociception and endocannabinoid-mediated stress-induced analgesia

“…Different parameters and durations of stress activate either opioid-dependent or opioid-independent analgesic mechanisms (Lewis et al, 1980;Terman et al, 1996). Previous work from our laboratories demonstrated that the coordinated release of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide mediates opioid-independent stress antinociception by engaging cannabinoid CB 1 receptors Suplita II et al, 2005. This discovery is consistent with the hypothesis that endocannabinoids, released under physiological conditions, produce adaptive changes in pain responses.…”

“…Our previous work demonstrated that opioid-independent stress antinociception is mediated by mobilization of endocannabinoids and subsequent activation of cannabinoid CB 1 receptors Suplita II et al, 2005. In these studies, pharmacological blockade of CB 1 with rimonabant or the structurally similar CB 1 antagonist AM251 blocked the antinociceptive effects of stress.…”

“…Stress antinociception was induced by exposure to continuous footshock (0.9 mA, AC current for 3 min (Lewis et al, 1980)), as described in our previously published work Suplita II et al, 2005. Stress antinociception was quantified using the tailflick test (D'Amour and Smith, 1941).…”

“…Nonetheless, due to the potential for such confounds, it is necessary to demonstrate that apparent antinociceptive effects observed in behavioral studies are not experimental artifacts attributable to motor suppression. Here we examine the effects of the stressor used in our previous studies to induce stress antinociception (Connell et al, 2006;Hohmann et al, 2005;Suplita II et al, 2005; on the ambulatory behavior of rats. These studies demonstrate that the ability of rimonabant to attenuate stress antinociception cannot be attributed to changes in basal locomotor activity.…”