Persistent Fos protein expression after orofacial deep or cutaneous tissueinflammation in rats: Implications for persistent orofacial pain

This study was designed to systematically examine the effects of persistent orofacial tissue injury on prolonged neuronal activation in the trigeminal nociceptive pathways by directly comparing the effects of orofacial deep v s. cutaneous tissue inflammation on brainstem Fos protein expression, a mar ker of neuronal activation. Complete Freund's adjuvant (CFA) was injected u nilaterally into the rat temporomandibular joint (TMJ) or perioral (PO) ski n to produce inflammation in deep or cutaneous tissues, respectively. Rats were perfused 2 hours, 24 hours, 3 days, or 10 days following CFA injection . The TMJ and PO inflammation-induced Fos expression paralleled the intensi ty and course of inflammation over the 10-day observation period, suggestin g that the increase in intensities and persistence of Fos protein expressio n may be associated with a maintained increase in peripheral input. Compare d to PO CFA injection, the injection of CFA into the TMJ produced a signifi cantly stronger inflammation associated with a greater Fos expression. In T MJ- but not in PO-inflamed rats, Fos-like immunoreactivity (LI) spread from superficial to deep upper cervical dorsal horn as the inflammation persist ed and there was a dominant ipsilateral Fos-labeling in the paratrigeminal nucleus. Common to TMJ and PO inflammation, Fos-LI was induced in the trige minal subnuclei interpolaris and caudalis, C1-2 dorsal horn, and other medu llary nuclei. Substantial bilateral Fos-LI was found in the interpolaris-ca udalis trigeminal transition zone. Further analysis revealed that Fos-LI in the ventral transition zone was equivalent bilaterally, whereas Fos-LI in the dorsal transition zone was predominantly ipsilateral to the inflammatio n. The differential induction of Fos expression suggests that an increase i n TMJ C-fiber input after inflammation and robust central neuronal hyperexc itability contribute to persistent pain associated with temporomandibular d isorders. J. Comp. Neurol. 412:276-291, 1999. (C) 1999 Wiley-Liss, Inc.