INCREASED IN-VIVO RELEASE OF CALCITONIN-GENE-RELATED PEPTIDE-LIKE MATERIAL FROM THE SPINAL-CORD IN ARTHRITIC RATS

Possible alterations in spinal systems containing calcitonin gene-rela ted peptide (CGRP) due to polyarthritis were assessed in rats 3-4 week s after an intradermal injection of Freund's adjuvant in the low back. The tissue levels of CGRP-like material (CGRPLM) were approximately 5 0% higher in the dorsal zone of the spinal cord and dorsal root gangli a at both the cervical and lumbar (but not thoracic) segments in polya rthritic rats than in age-paired control animals. In addition the rate of the spinal release of CGRPLM determined through an intrathecal per fusion procedure in halothane-anaesthetized animals was approximately 15-fold higher in polyarthritic rats than in controls. The blockade of mu-opioid receptors by intrathecal perfusion with 10 muM naloxone pro duced a larger increase in the spontaneous CGRPLM outflow in polyarthr itic rats than in age-paired controls. Furthermore, the stimulation of mu-opioid receptors by intrathecal perfusion with 10 muM DAGO signifi cantly inhibited the spinal outflow of CGRPLM only in polyarthritic ra ts. These data indicate that CGRP-containing primary afferent fibres a re markedly activated in chronic suffering polyarthritic rats. This ac tivation occurs in spite of an increased tonic inhibitory control by e ndogenous opioids acting at mu receptors.