SPINAL RELEASE OF IMMUNOREACTIVE DYNORPHIN A((1-8)) WITH THE DEVELOPMENT OF PERIPHERAL INFLAMMATION IN THE RAT

Microprobes bearing immobilised antibodies to dynorphin A((1-8)) were used to study the basal and evoked release of this prodynorphin derive d peptide in the spinal cord of urethane anaesthetised normal rats and those with a peripheral inflammation. In the absence of any active pe ripheral stimulus the antibody microprobes detected immunoreactive (ir )-dynorphin A((1-8)) in two areas (lamina I and laminae IV-V) in the d orsal horn of the spinal cord of normal rats. With the development of unilateral ankle inflammation over 3 to 5 days following subcutaneous injections of Freund's complete adjuvant, a basal presence of ir-dynor phin A((1-8)) was found in both the dorsal and ventral horn regions of both sides of the spinal cord. Lateral compression of the ankles of t he normal animals did not release ir-dynorphin A((1-8)) during the per iod of stimulation, but this neuropeptide was detected in increased am ounts in the ventral horn following the stimulus. By contrast, compres sion of inflamed ankles produced elevated levels of ir-dynorphin A((1- 8)) during the period of stimulus application at three major sites in the ipsilateral spinal grey matter. The largest peak was in the deep d orsal horn/upper ventral horn (laminae VI-VII), with further sites of significant release in the mid dorsal horn (laminae II-V) and the lowe r ventral horn. The observation that ir-dynorphin A((1-8)) is physiolo gically released in the ventral and deep dorsal in addition to the sup erficial dorsal horn of the rat suggests an involvement of dynorphins in several aspects of spinal function.