Stage-dependent C-reflex, pain-like behavior and opioid analgesia during the induction of chronic arthritis in rats

• Published in: The European journal of neuroscience 2014-10, Vol.40 (8), p.3264-3272
• Main Authors: Alvarez, Pedro, Hernández, Alejandro, Constandil, Luis, Infante, Claudio, Pelissier, Teresa
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - pharmacology; Animals; arthritic pain; Arthritis - chemically induced; Arthritis - complications; Biological and medical sciences; Chronic Disease; Disease Progression; Diseases of the osteoarticular system; Electric Stimulation; Electromyography; Freund's Adjuvant - toxicity; Hindlimb - physiopathology; Male; mechanical hyperalgesia; Medical sciences; Miscellaneous. Osteoarticular involvement in other diseases; morphine; Nerve Fibers, Unmyelinated - physiology; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Nociception - drug effects; Nociception - physiology; Pain - physiopathology; Pain - prevention & control; Rats; Rats, Sprague-Dawley; reflex response; Reflex, Stretch
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12685

Chronic arthritis (CA) is a common clinical entity associated with persistent pain and limited response to opioid analgesic therapy. However, it is unknown whether these features of CA change depending on its stage of evolution. To address this, in a well‐established animal model of CA we studied the time course of electromyographic responses to electrical stimulation of C fibers (C‐reflex), pain‐like 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‐reflex responses to electrical stimuli or the nociceptive response to paw pressure test were studied 2, 4 or 6 weeks later. The C‐reflexes evoked by threshold and supra‐threshold 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‐reflex and pain‐like responses evolve in parallel, and are inhibited by morphine in a stage‐dependent 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. A limited response to opioid analgesic therapy is common in chronic arthritis and it is unknown whether these features change depending on its stage of evolution. Rats were studied at 2, 4 or 6 weeks of monoarthritis in C‐reflex response and paw pressure test. Morphine was a reduced effect during 2‐week of monoarthritis and enhanced at 4 and 6‐week of monoarthritis. These results may contribute to explain the variable analgesic efficacy of opioids that characterizes arthritic pain in humans.