Kappa opioid signaling in the right central amygdala causes hind paw specific loss of diffuse noxious inhibitory controls in experimental neuropathic pain
AffiliationDepartment of Pharmacology
Kappa opioid receptor
Diffuse noxious inhibitory controls
Conditioned pain modulation
Descending pain modulation
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CitationPhelps CE, Navratilova E, Dickenson AH, Porreca F, Bannister K. Kappa Opioid Signaling in the Right Central Amygdala Causes Hindpaw Specific Loss of Diffuse Noxious Inhibitory Controls (DNIC) in Experimental Neuropathic Pain. Pain 2019
Rights© 2019 International Association for the Study of Pain.
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AbstractDiffuse noxious inhibitory controls (DNICs) is a pain-inhibits-pain phenomenon demonstrated in humans and animals. Diffuse noxious inhibitory control is diminished in many chronic pain states, including neuropathic pain. The efficiency of DNIC has been suggested to prospectively predict both the likelihood of pain chronification and treatment response. Little is known as to why DNIC is dysfunctional in neuropathic pain. Here, we evaluated DNIC in the rat L5/L6 spinal nerve ligation (SNL) model of chronic pain using both behavioral and electrophysiological outcomes. For behavior, nociceptive thresholds were determined using response to noxious paw pressure on both hind paws as the test stimulus before, and after, injection of a conditioning stimulus of capsaicin into the left forepaw. Functionally, the spike firing of spinal wide-dynamic-range neuronal activity was evaluated before and during noxious ear pinch, while stimulating the ipsilateral paw with von Frey hairs of increased bending force. In both assays, the DNIC response was significantly diminished in the ipsilateral (ie, injured) paw of SNL animals. However, behavioral loss of DNIC was not observed on the contralateral (ie, uninjured) paw. Systemic application of nor-binaltorphimine, a kappa opioid antagonist, did not ameliorate SNL-induced hyperalgesia but reversed loss of the behavioral DNIC response. Microinjection of nor-binaltorphimine into the right central amygdala (RCeA) of SNL rats did not affect baseline thresholds but restored DNIC both behaviorally and electrophysiologically. Cumulatively, these data suggest that net enhanced descending facilitations may be mediated by kappa opioid receptor signaling from the right central amygdala to promote diminished DNIC after neuropathy.
Note12 month embargo; publication date: 1 July 2019
VersionFinal accepted manuscript
SponsorsThis work was supported by grants from the National Institutes of Health (NS106902 and DA041809) and by the Wellcome Trust Pain Consortium .