A new animal model for assessing mechanisms and management of muscle hyperalgesia

Musculoskeletal pain is one of the most frequent symptoms for which medical assistance is sought. Yet, the majority of our knowledge regarding pain ph ysiology is based on studies of cutaneous tissue. Comparatively little is k nown about activation of visceral, joint and perhaps least of all, musculos keletal nociceptors although clinically-treated pain originates principally in these structures. Studies elucidating the mechanisms of muscle hyperalg esia have been hampered by the lack of an animal model that permits the eva luation of hypotheses using behavioral, biochemical, pharmacological, anato mical and molecular experimental approaches. Here we describe an animal mod el of muscle hyperalgesia we recently developed that permits such multidisc iplinary investigation. This model employs the intramuscular injection of c arrageenan, a chemical stimulus which evokes a well recognized model of cut aneous inflammation and is reported to activate muscle nociceptors. Intramu scular carrageenan evokes a time- and dose-dependent reduction in forelimb grip force that is anatomically specific. The carrageenan-evoked reduction in grip force is blocked by the mu-opioid agonist levorphanol in a dose-dep endent, stereoselective and naltrexone-reversible manner. This behavioral d ependent measure is also significantly reversed by agents used clinically t o treat muscle pain, indomethacin and dexamethasone, as well as the non-com petitive N-methyl-D-aspartate receptor antagonist MK801. Finally, evidence that reduction in grip force is in part mediated by small, unmyelinated aff erents is provided by the demonstration that neonatal capsaicin treatment s ignificantly reduced carrageenan-evoked behavioral hyperalgesia (similar to 45% reduction) and reduced muscle content of immunoreactive CGRP (similar to 60% reduction) relative to control levels. Collectively, these findings provide converging lines of evidence for the validity of this animal model to investigate mechanisms involved in the development of muscle hyperalgesi a. (C) 2000 International Association for the Study of Pain. Published by E lsevier Science B.V. All rights reserved.