Injection of adjuvant but not acidic saline into craniofacial muscle evokes nociceptive behaviors and neuropeptide expression

Abstract

Craniofacial muscle pain including muscular temporomandibular disorders accounts for a substantial portion of all pain perceived in the head and neck region. In spite of its high clinical prevalence, the mechanisms of chronic craniofacial muscle pain are not well understood. Injection of acidic saline into rodent hindlimb muscles produces pathologies which resemble muscular pathologies in chronic pain patients. Here we investigated whether analogous transformations occur following repeated injections of acidic saline into the rat masseter muscle. Injection of acidic saline (pH 4) into the masseter muscle transiently lowered intramuscular pH to levels comparable to those reported for rodent hindlimb muscles. Nevertheless, repeated unilateral or bilateral injections of acidic saline (pH 4) into the masseter muscle failed to alter nociceptive behavioral responses as occurs in the hindlimb. Changing the pH of injected saline to pH 3.0 or 5.0 also did not evoke nocifensive behavior. ASIC3 receptors, which are implicated in transformations following acidification of hindlimb muscles, were found on trigeminal ganglion muscle afferent neurons via combined neuronal tracing and immunocytochemistry. In contrast to the acidic saline, injection of complete Freund's adjuvant (CFA) into the masseter muscle induced mechanical allodynia for three weeks, thermal hyperalgesia for one week and an increase in the number of CGRP-immunoreactive muscle afferent neurons in the trigeminal ganglion. Although pH may alter CGRP release in primary afferent neurons, the number of CGRP-muscle afferent neurons did not change following intramuscular injection of acidic saline. Further, there was no change in ganglionic iCGRP levels at one, four or twelve days after intramuscular injection of acidic saline. While these findings extend our earlier reports that CFAinduced muscle inflammation results in behavioral and neuropeptide changes they further suggest that intramuscular acidification in craniofacial muscle evokes different responses than in hindlimb muscle and imply that disparate proton sensing mechanisms underlie these discrepancies. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 November 9. Published in final edited form as:Neuroscience. 2007 November 9; 149(3): 650-659. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptFifteen percent of the American population suffers from chronic musculoskeletal pain, placing a substantial burden on the health care system (Magni et al., 1993;...

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