Phelps, CE;
Navratilova, E;
Dickenson, AH;
Porreca, F;
Bannister, K;
(2019)
Kappa opioid signaling in the right central amygdala causes hind paw specific loss of diffuse noxious inhibitory controls in experimental neuropathic pain.
Pain
, 160
(7)
pp. 1614-1621.
10.1097/j.pain.0000000000001553.
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Abstract
Diffuse noxious inhibitory controls (DNIC) is a pain inhibits pain phenomenon demonstrated in humans and animals. DNIC 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 hindpaws 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 (WDR) neuronal activity was evaluated before and during noxious ear pinch, whilst stimulating the ipsilateral paw with von Frey hairs of increased bending force. In both assays, the DNIC response was significantly diminished in the ipsilateral (i.e., injured) paw of SNL animals. However, behavioral loss of DNIC was not observed on the contralateral (i.e., uninjured) paw. Systemic application of nor-Binaltorphimine (nor-BNI), a kappa opioid antagonist, did not ameliorate SNL-induced hyperalgesia but reversed loss of the behavioral DNIC response. Microinjection of nor-BNI 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 RCeA to promote diminished DNIC following neuropathy.
| Type: | Article |
|---|---|
| Title: | Kappa opioid signaling in the right central amygdala causes hind paw specific loss of diffuse noxious inhibitory controls in experimental neuropathic pain |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/j.pain.0000000000001553 |
| Publisher version: | https://doi.org/10.1097/j.pain.0000000000001553 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | neuropathic pain; Amygdala; Kappa opioid receptor; Diffuse Noxious Inhibitory Controls; conditioned pain modulation; Descending Pain Modulation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10071004 |
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