The effects of stress-induced analgesia and peripherally-administered cannabinoid receptor antagonists on formalin-induced pain behavior
Feistritzer, Rebecca Carter
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Stress-induced analgesia (SIA) occurs when naturally occurring brain constituents inhibit pain pathways upon exposure to a stressor and provide pain relief. These pathways involve cannabinoid receptors (CB1 and CB2) and their activation by their natural ligands, the endocannabinoids. The CB1antagonist AM251 and CB2 antagonist SR144528 were used to block CB1 and CB2 receptors. The formalin test serves as a useful rodent model of pain in that an intradermal formalin injection inflicts two phases of pain behavior separated by a quiescent interval. Pain behaviors can be analyzed via quantification of time spent lifting, licking, or shaking the injected paw. These experiments were designed to compare the effects of SIA on formalin-induced pain and identify the role of peripherally-mediated cannabinoid receptors in contributing to endocannabinoid-mediated SIA in the formalin model. First, rats were exposed to footshock to induce SIA before injections of varying concentrations of formalin. The composite pain score (CPS) of pain behavior of shocked and non-shocked rats increased with increasing formalin concentrations, but was significantly lower overall in shocked rats. Thus, SIA effectively suppressed formalin-induced pain sensation. Next, AM251 and SR144528 were intradermally to the paw before SIA induction and formalin injections. In animals subjected to footshock, SR144528 increased phase 1 pain behavior compared to vehicle controls. By contrast, neither SR144528 nor AM251, administered locally in the paw. increased phase 2 behavior. In summary, SIA is effective at reducing formalin-induced pain, and blockade of cannabinoid CB2 receptors in the paw attenuates SIA. Thus, peripherally-located CB2 receptors play a role in stress-induced analgesia in the formalin test.