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    Kappa opioid signaling in the right central amygdala causes hind paw specific loss of diffuse noxious inhibitory controls in experimental neuropathic pain

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    Author
    Phelps, Caroline E
    Navratilova, Edita
    Dickenson, Anthony H
    Porreca, Frank
    Bannister, Kirsty
    Affiliation
    Department of Pharmacology
    Issue Date
    2019-07-01
    Keywords
    Neuropathic pain
    Amygdala
    Kappa opioid receptor
    Diffuse noxious inhibitory controls
    Conditioned pain modulation
    Descending pain modulation
    
    Metadata
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    Publisher
    Wolters Klower
    Citation
    Phelps 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
    Journal
    PAIN
    Rights
    © 2019 International Association for the Study of Pain.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Diffuse 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.
    Note
    12 month embargo; publication date: 1 July 2019
    ISSN
    0304-3959
    EISSN
    1872-6623
    PubMed ID
    30870321
    DOI
    10.1097/j.pain.0000000000001553
    Version
    Final accepted manuscript
    Sponsors
    This work was supported by grants from the National Institutes of Health (NS106902 and DA041809) and by the Wellcome Trust Pain Consortium [102645].
    ae974a485f413a2113503eed53cd6c53
    10.1097/j.pain.0000000000001553
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