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However, it is unknown whether these features of CA change depending on its stage of evolution. To address this, in a well\u2010established animal model of CA we studied the time course of electromyographic responses to electrical stimulation of C fibers (C\u2010reflex), pain\u2010like behavior as a response to mechanical nociceptive stimulation, and the inhibition of both responses by a prototypic opioid analgesic, morphine. To induce CA, rats received a single injection of complete Freund's adjuvant into the ankle joint and the C\u2010reflex responses to electrical stimuli or the nociceptive response to paw pressure test were studied 2, 4 or 6\u00a0weeks later. The C\u2010reflexes evoked by threshold and supra\u2010threshold electrical stimulation exhibited progressive increases together with enhancement of the nociceptive behavior to mechanical stimulation during induction of monoarthritis. Notably, while systemic morphine produced antinociceptive effects upon both experimental approaches, the effects were markedly reduced during the early stages of CA but enhanced at later stages. These data indicate that C\u2010reflex and pain\u2010like responses evolve in parallel, and are inhibited by morphine in a stage\u2010dependent manner through the induction of CA. The present results may contribute to explain the enhanced pain response and variable analgesic efficacy of opioids that characterize arthritic pain in humans.<\/jats:p>","DOI":"10.1111\/ejn.12685","type":"journal-article","created":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T12:36:50Z","timestamp":1408624610000},"page":"3264-3272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Stage\u2010dependent C\u2010reflex, pain\u2010like behavior and opioid analgesia during the induction of chronic arthritis in rats"],"prefix":"10.1111","volume":"40","author":[{"given":"Pedro","family":"Alvarez","sequence":"first","affiliation":[{"name":"Program of Molecular and Clinical Pharmacology Institute of Biomedical Sciences (ICBM) Faculty of Medicine University of Chile Independencia 1027, PO Box 70000 Santiago 7 Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology Department of Biology Faculty of Chemistry and Biology University of Santiago of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Constandil","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology Department of Biology Faculty of Chemistry and Biology University of Santiago of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Infante","sequence":"additional","affiliation":[{"name":"Program of Physiopathology Institute of Biomedical Sciences (ICBM) Faculty of Medicine University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Pelissier","sequence":"additional","affiliation":[{"name":"Program of Molecular and Clinical Pharmacology Institute of Biomedical Sciences (ICBM) Faculty of Medicine University of Chile Independencia 1027, PO Box 70000 Santiago 7 Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,8,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-2391(03)00678-5"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(02)00020-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200112210-00010"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)94830-O"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.27"},{"key":"e_1_2_8_7_1","first-page":"879","article-title":"Is IL\u20101 a good therapeutic target in the treatment of arthritis? 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