Corticotropin-releasing factor in the rat amygdala differentially influences sensory-discriminative and emotional-like pain response in peripheral neuropathy

The central nucleus of the amygdala (CeA) is involved in processing and regulation of pain. We determined whether amygdaloid corticotropin-releasing factor (CRF) contributes to pain modulation in the neuropathic rat. Emotional aspect of pain was assessed by an aversive place-conditioning test and sensory aspect of pain by determining monofilament-induced limb-withdrawal threshold. CRF_6-33 (an inhibitor of CRF-binding protein) or CRF_9-41, a nonselective CRF receptor antagonist, was microinjected to the left or right CeA or a control site in rats with spared nerve injury (SNI) or sham operation of the left hind limb. In SNI animals, CRF_6-33 in the left or right CeA, but not in a control site, attenuated emotional painlike behavior and increased sensory pain. In sham controls, CRF_6-33 in the right but not left CeA increased sensory aspect of pain, without influence on place-avoidance behavior. The effects induced by CRF_6-33 were reversed by CRF_9-41. The results indicate that endogenous CRF in the CeA, through action on CRF receptors, may differentially influence emotional and sensory aspects of pain in neuropathy. While the right CeA had a dominant role in modulation of pain-related responses in sham controls, left as well as right CeA contributed to pain modulation in neuropathic animals. Perspective: An increase in free endogenous corticotropin-releasing factor in the central nucleus of the amygdala was accompanied by increased cutaneous hypersensitivity and decreased emotional painlike behavior in neuropathic animals. This finding indicates that CRF in the amygdala may have differential effects on sensory and emotional aspects of neuropathic pain.