PERIPHERAL AND CENTRAL CONTRIBUTIONS TO THE PERSISTENT EXPRESSION OF SPINAL-CORD FOS-LIKE IMMUNOREACTIVITY PRODUCED BY SCIATIC-NERVE TRANSECTION IN THE RAT

Previous studies have demonstrated that noxious stimuli, intense enoug h to produce tissue injury, evoke a transient expression of the Fos pr otein product of the c-fos proto-oncogene in neurons, in regions of th e spinal cord that contribute to the transmission of nociceptive messa ges in the rat. Since there is evidence that increases in fos-like imm unoreactivity reflect increases in neuronal activity, it has thus been possible to identify populations of neurons that are activated in res ponse to tissue injury. In this study we used immunocytochemical local ization of fos-like immunoreactive (FLI) neurons to map the patterns o f neuronal activity in the spinal cord at different times after periph eral nerve injury in the rat. Sciatic nerve transection induced a pers istent (at least 1 month) elevation in the number of FLI neurons, pred ominantly in laminae 1, 2, 5, 6 and 7 of the ipsilateral lumbar enlarg ement of the spinal cord. In the L5 segment, the expression of fos-lik e immunoreactivity in the superficial dorsal horn (laminae 1 and 2) fl uctuated, with peaks of Fos expression at 2 h, 2 days and 2 weeks afte r nerve transection. Furthermore, by 2 weeks after nerve injury, the d istribution of labelled neurons in the superficial laminae of the dors al horn shifted, with the most densely labelled cells now located in t he central portion of the superficial dorsal horn. In contrast, the pa ttern of labelled neurons in laminae 5, 6 and 7 was relatively constan t over the 4-week study period. Local anesthetic block of the sciatic nerve significantly decreased the number of FLI neurons when it was ad ministered at either 2 days or 2 weeks post nerve injury. At 2 days, i njection of the local anesthetic subcutaneously in the dorsum of neck, to control for a systemic action, also reduced expression of FLI in l aminae 1 and 2; at 2 weeks, the systemic injection of the local anesth etic reduced expression of FLI throughout the gray matter of the spina l cord. These results demonstrate that peripheral nerve injury, in con trast to tissue injury, induces a prolonged increase in Fos expression in neurons predominantly in those regions of the spinal cord that are associated with the transmission of nociceptive messages. This patter n of fos-like immunoreactivity is probably the result of persistent ne uronal activity in the spinal cord. The increased 'activity' in the sp inal cord appears to be maintained both by abnormal activity in the in jured peripheral nerve as well as by reorganization of circuits within the spinal cord secondary to the nerve injury.