ENKEPHALINERGIC AND DYNORPHINERGIC NEURONS IN THE SPINAL-CORD AND DORSAL-ROOT GANGLIA OF THE POLYARTHRITIC RAT - IN-VIVO RELEASE AND CDNA HYBRIDIZATION STUDIES

Complex and contradictory data have been reported regarding the change s in spinal opioidergic systems associated with chronic inflammatory p ain in the rat. In an attempt to solve these discrepancies, the in viv o release of met-enkephalin and dynorphin and the expression of the co rresponding propeptide genes were investigated at the spinal level in arthritic rats and paired controls. A dramatic increase in the concent ration of prodynorphin mRNA (+300-550%) and a less pronounced elevatio n of that of dynorphin-like material (+40-50%) were found in the dorsa l part of cervical and lumbar segments of the spinal cord in rats rend ered arthritic by an intradermal injection of Freund's adjuvant four w eeks prior to these measurements. In addition, the spinal release of d ynorphin-like material (assessed through an intrathecal perfusion proc edure in halothane-anaesthetized animals) was approximately twice as h igh in arthritic rats as in controls. In spite of significant elevatio ns in the levels of both met-enkephalin (+30-70%) and proenkephalin A mRNA (+40-50%) in the dorsal part of cervical and lumbar segments, the spinal release of metenkephalin-like material was decreased (-50%) in arthritic rats as compared to paired controls. Proenkephalin A mRNA ( but not prodynorphin mRNA) could be measured in dorsal root ganglia, a nd its levels were dramatically reduced in ganglia at the lumbar segme nts in arthritic rats. Such parallel reductions in the spinal release of met-enkephalin-like material and the levels of proenkephalin A mRNA in dorsal root ganglia of arthritic rats support the idea that the ac tivity of primary afferent enkephalinergic fibres decreases markedly d uring chronic inflammatory pain.