EFFECTS OF MORPHINE AND NALOXONE ON BASAL AND EVOKED FOS-LIKE IMMUNOREACTIVITY IN LUMBAR SPINAL-CORD NEURONS OF ARTHRITIC RATS

We have previously shown, on the one hand, that the number of Fos-like immunoreactive (Fos-LI) neurons in the lumbar spinal cord observed during the development of adjuvant-induced arthritis in the rat correlates with the clinical and behavioral scores and, on the other hand, that the number of Fos-LI neurons induced by repeated mechanical pressure to the ankle was greater in arthritic animals than in healthy ones. In non-stimulated arthritic rats, Fos-LI neurons were mainly present in the neck of the dorsal horn and in the ventral horn of L3-L5, whereas following stimulation they were numerous in the superficial laminae. The aim of this study was to evaluate Fos-LI following morphine injection (1) in arthritic animals in the absence of any stimulation, (2) in arthritic rats after ankle stimulation pretreated with morphine or by the combination of morphine and naloxone, and (3) following naloxone treatment in non-stimulated and stimulated polyarthritic rats. In non-stimulated arthritic rats, a single morphine injection (1-9 mg/kg, i.v.) or a single naloxone injection (1-3 mg/kg, i.v.) induced no change in the basal Fos-LI present in lumbar spinal neurons. In contrast, Fos-LI evoked by noxious pressure was strongly depressed by morphine. In the superficial laminae pretreatment with a single morphine injection of either 0.5 or 1 mg/kg, i.v., reduced by more than 50% the number of Fos-LI neurons and at 3 mg/kg completely abolished the labeling evoked by the stimulation. Similar effects were obtained in the neck of the dorsal horn. These effects were reversed by naloxone (morphine 3 mg/kg and naloxone 0.3 mg/kg). Pretreatment with naloxone (1 mg/kg) did not change Fos labeling. This study which is based on mechanical stimulation in arthritic rats confirms and extends previous investigations and demonstrates that the use of Fos-LI is a suitable method to reveal the efficacy of opioid analgesic. However, the lack of effects of opioids on basal labeling suggests that long-term drug treatment should be used to study the effects of various putative analgesics on chronic pain models.