MODULATED EXPRESSION OF C-FOS IN THE SPINAL-CORD FOLLOWING NOXIOUS THERMAL-STIMULATION OF MONOARTHRITIC RATS

Peripheral noxious stimulation evokes functional and biochemical chang es in the spinal cord which results in central sensitization and hyper algesia, but at the same time also induces the activation of inhibitor y control systems. The purpose of the present study was to investigate whether the adaptive changes induced by ongoing peripheral inflammati on influence the spinal cord expression of c-Fos (a commonly used mark er of neuronal activity) following an additional acute noxious stimulu s. Therefore, the spinal expression of c-Fos was immunohistochemically investigated following noxious thermal stimulation of a rat monoarthr itic hindpaw at various time points (1, 4, 8, 21 days) after induction of monoarthritis. Compared to normal rats, c-Fos expression following ipsilateral noxious thermal stimulation of monoarthritic rats was str ongly modified in the deep laminae of the dorsal horn depending on the time course of inflammation. At 1 day of monoarthritis, an enhanced i psilateral expression (135% and 208% of normal rats in laminae III-VI and VII, respectively) and at 3 weeks a reduced expression (38% and 23 % of normal rats in laminae III-VI and VII, respectively) was detected . The amount of c-Fos-positive neurons in the ipsilateral superficial laminae I and II was unchanged at all time points investigated. To ass ess excitability changes on the contralateral side at an early stage o f inflammation, a group of monoarthritic rats received a contralateral noxious stimulus at day 1 of monoarthritis. This resulted in a potent iated expression of c-Fos ipsilateral to the acute noxious stimulus (i .e., contralateral to the monoarthritic hindpaw) restricted to lamina II (137% of normal rats) of the dorsal horn. The data showed that chan ges in c-Fos expression depended on the time point of noxious heat sti mulation (NHS) of monoarthritic rats, and differed in the ipsi- and co ntralateral side of the spinal cord. In addition to a possible habitua tion of c-Fos expression, it may be speculated that the time course-de pendent changes reflect laminae-specific modulations of excitatory and inhibitory mechanisms during monoarthritis. Further studies are neces sary in order to provide more insights into the contribution of these mechanisms on noxious stimulus-evoked c-Fos expression. J. Neurosci. R es. 53:203-213, 1998. (C) 1998 Wiley-Liss, Inc.