Cb1 Receptor Activation in the Basolateral Amygdala Produces Antinociception in Animal Models of Acute and Tonic Nociception

Abstract

1. Recent studies have suggested that the basolateral nucleus of the amygdala (BLA) participates in the processing of pain information, especially noxious somatic information. Cannabinoid receptors or CB1 mRNA are expressed more in the BLA than in other nuclei of the amygdala. Thus, the aim of the present study was to examine whether CB1 receptors in the BLA may be involved in modulating acute and/or tonic nociceptive processing. 2. Adult rats were exposed to intra-BLA microinjection of the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo [1,2,3,-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate [WIN 55,212-2 (1, 2.5, 5 or 10 microg/side)] and subjected to the tail flick and formalin tests. 3. The rats demonstrated a dose-dependent increase in latency to withdraw from a thermal noxious stimulus in the tail flick test and a decrease in formalin-induced pain behaviours. The antinociceptive effects of the CB1 receptor agonist WIN 55,212-2 (10 microg/side) in both tests were attenuated in the presence of the selective CB1 receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamide (AM251; 0.55 ng/side). Administration of the CB1 receptor antagonist AM251 (0.55, 5.5, or 55.5 ng/side) alone did not alter the nociceptive thresholds in either test. Bilateral microinjection of the selective CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 1 microg/side) had no effect on the antinociception produced by WIN 55,212-2, suggesting that the antinociceptive actions of WIN 55,212-2 are mediated by CB1 receptors. 4. The findings suggest the existence of a CB1-mediated inhibitory system in the BLA that, when activated, can diminish responsivity to acute and tonic noxious stimuli, but that normally has no tonic effect on the response threshold of these stimuli.

Evidence for a novel functional role of cannabinoid CB2 receptors in the thalamus of neuropathic rats

“…Previously, intralateral posterior thalamic microinjection of the mixed CB 1 and CB 2 receptor agonist WIN55212 attenuated nociceptive behavioural processing in naïve rats (Martin et al ., 1999), although the receptor mediating this effect was not further investigated. In other brain regions, such as the amygdala, the antinociceptive effects of intrabasolateral amygdala injection of WIN55212 in formalin and tail‐flick tests were abolished by CB 1 receptor antagonism but not CB 2 receptor antagonism in naïve rats (Hasanein et al ., 2007). Further support for a lack of functional role of supraspinal CB 2 receptors was provided by the report that intracerebroventricular injection of JWH‐133 did not alter formalin‐evoked nociceptive responses (Jafari et al ., 2007).…”

The effect of CB1 receptor antagonism in the right basolateral amygdala on conditioned fear and associated analgesia in rats

“…Moreover, the modulation of fear-related freezing and ultrasonic vocalizations towards the end of the trial suggests that SR141716A was biologically active throughout the test period. In a recent study, intra-BLA administration of AM251, a structurally related analogue of SR141716A, did not alter nociceptive behaviour in the formalin test (Hasanein et al, 2007). However, direct comparisons between these two studies are difficult due to methodological differences, including time of antagonist administration and duration of behavioural observation.…”

Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model

“…Exogenous cannabinoids reduce responsiveness to noxious thermal, chemical and mechanical stimuli in rats. Cannabinoids induce antinociception by acting in neuroanatomical regions subserving transmission and modulation of pain signals, including, the periaqueductal gray (PAG) [33,34] and the basolateral nucleus of amygdala [35]. The analgesic effect of endocannabinoids can be attributed in part to a neuronal mechanism based on the activation of CB 1 receptors expressed in primary afferent neurons.…”