{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:02:47Z","timestamp":1786618967175,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/87537\/2012"],"award-info":[{"award-number":["SFRH\/BPD\/87537\/2012"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004323","name":"Amylin Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Amylin is a calcitonin gene\u2010related peptide family member expressed by nociceptors. Amylin's expression is down\u2010regulated 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2010receptor antagonist (AC187) or vehicle solutions were delivered chronically, by a subcutaneous (SC) mini\u2010osmotic 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Continuous subcutaneous amylin administration aggravated cold allodynia in SNI animals, possibly via amylin\u2010receptors (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\u2010Fos 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Amylin's nociceptive effects seem to depend on the treatment duration and route of administration by acting at different levels of the nervous system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>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\u2010 and antinociceptive effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.1347","type":"journal-article","created":{"date-parts":[[2018,12,2]],"date-time":"2018-12-02T21:43:23Z","timestamp":1543787003000},"page":"784-799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Amylin, a peptide expressed by nociceptors, modulates chronic neuropathic pain"],"prefix":"10.1002","volume":"23","author":[{"given":"L\u00edgia Sofia","family":"Almeida","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto Porto Portugal"},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto Porto 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