Amylin, a peptide expressed by nociceptors, modulates chronic neuropathic pain

Abstract

Background

Amylin is a calcitonin gene‐related peptide family member expressed by nociceptors. Amylin's expression is down‐regulated following nerve damage, and studies suggested it affects nociception. We aimed at clarifying amylin's effects on chronic neuropathic pain and investigating its site of action.

Methods

Chronic neuropathic pain was induced in rats by spared nerve injury (SNI) surgery. Mechanical allodynia/hyperalgesia and cold allodynia/hyperalgesia were assessed by the von Frey, pinprick, acetone and cold plate behavioural tests, respectively. Amylin, amylin‐receptor antagonist (AC187) or vehicle solutions were delivered chronically, by a subcutaneous (SC) mini‐osmotic pump, or acutely, by SC or intrathecal (IT) injections. Cellular and fibre markers were used to detect spinal cord alterations in SNI rats after chronic amylin administration.

Results

Continuous subcutaneous amylin administration aggravated cold allodynia in SNI animals, possibly via amylin‐receptors (AmyR) in supraspinal areas. Acute intrathecal administration of amylin attenuated mechanical hyperalgesia, whereas AC187 reduced mechanical allodynia, suggesting distinct roles of endogenous amylin and of pharmacological amylin doses when targeting spinal cord amylin receptors. Chronic amylin administration promoted c‐Fos activation only in the dorsal horn neurons of SHAM animals, suggesting a distinctive role of amylin in the activation of the spinal neuronal circuitry under neuropathic and physiological conditions. ERK1/2 phosphorylation increased in the dorsal horn neurons of SNI rats chronically treated with amylin. This ERK1/2 cascade activation may be related to amylin's effect on the aggravation of cold allodynia in SNI rats.

Conclusions

Amylin's nociceptive effects seem to depend on the treatment duration and route of administration by acting at different levels of the nervous system.

Significance

Amylin modulated neuropathic pain by acting at different levels of the nervous system. Whereas supraspinal areas may be involved in amylin's induced pronociception, modulation of spinal cord amylin receptors by endogenous or pharmacological amylin doses triggers both pro‐ and antinociceptive effects.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/2UEXq3H
via IFTTT