{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:11:30Z","timestamp":1778134290389,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,25]],"date-time":"2015-05-25T00:00:00Z","timestamp":1432512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["20020"],"award-info":[{"award-number":["20020"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the contribution of sensory neurons in ankle joints and adjacent tissue to the development of pain in collagen\u2010induced arthritis (CIA), and to determine the relationship between pain and the appearance of clinical signs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mechanical and heat hypersensitivity and hind paw swelling were assessed in Lewis rats before and until 18 days following collagen immunization. We examined the effect of intrathecal administration of a calcitonin gene\u2010related peptide (CGRP) antagonist (CGRP<jats:sup>8\u201337<\/jats:sup>) from day 11 to day 18 postimmunization on CIA\u2010induced hypersensitivity. During CIA development, CGRP and p\u2010ERK immunoreactivity was quantified in lumbar dorsal root ganglia in which sensory neurons innervating the ankle joint were identified by retrograde labeling with Fluoro\u2010Gold. Microgliosis in the lumbar dorsal horn was assessed by immunohistochemistry, and release of CGRP evoked by activity of primary afferent fibers was measured using a preparation of isolated dorsal horn with dorsal roots attached.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CIA was associated with mechanical hypersensitivity that was evident before hind paw swelling and that was exacerbated with the development of swelling. Heat hyperalgesia developed along with swelling. Concomitant with the development of mechanical hypersensitivity, joint innervating neurons exhibited enhanced CGRP expression and an activated phenotype (increased p\u2010ERK expression), and significant microgliosis became evident in the dorsal horn; these peripheral and central changes were augmented further with disease progression. CGRP release evoked by dorsal root stimulation was higher in the dorsal horn on day 18 in rats with CIA compared to control rats. Prolonged intrathecal administration of CGRP<jats:sup>8\u201337<\/jats:sup> attenuated established mechanical hypersensitivity and reduced spinal microgliosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sensory neuron\u2013derived CGRP sustains mechanical hypersensitivity and spinal microglial reactivity in CIA, suggesting that central mechanisms play critical roles in chronic inflammatory pain. Blockade of these central events may provide pain relief in rheumatoid arthritis patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39082","type":"journal-article","created":{"date-parts":[[2015,2,23]],"date-time":"2015-02-23T11:19:21Z","timestamp":1424690361000},"page":"1668-1677","source":"Crossref","is-referenced-by-count":58,"title":["Calcitonin Gene\u2010Related Peptide\u2013Expressing Sensory Neurons and Spinal Microglial Reactivity Contribute to Pain States in Collagen\u2010Induced Arthritis"],"prefix":"10.1002","volume":"67","author":[{"given":"Francisco R.","family":"Nieto","sequence":"first","affiliation":[{"name":"King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna K.","family":"Clark","sequence":"additional","affiliation":[{"name":"King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Grist","sequence":"additional","affiliation":[{"name":"King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Chapman","sequence":"additional","affiliation":[{"name":"University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzia","family":"Malcangio","sequence":"additional","affiliation":[{"name":"King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,5,25]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"2006","article-title":"Subgrouping of patients with rheumatoid arthritis based on pain, fatigue, inflammation, and psychosocial factors. 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