PLASTICITY OF CALCITONIN-GENE-RELATED PEPTIDE NEUROTRANSMISSION IN THE SPINAL-CORD DURING PERIPHERAL INFLAMMATION

Injection of complete Freund's adjuvant (CFA; 75 mu L) into the planta r surface of the hind paw of the rat results in a mild inflammation th at lasts for several days and is accompanied by hyperalgesia. Multiple components of calcitonin gene related peptide (CGRP) neurotransmissio n in the spinal cord are altered during the course of this peripheral inflammation. The content of immunoreactive (i) CGRP in the dorsal hor n of the spinal cord, where primary afferent neurons terminate, is sig nificantly decreased within 2 days after injection of CFA but increase s to a level greater than that of the control at 8 days. The early dec rease in iCGRP in the spinal cord suggests that the release of CGRP fr om primary afferent neurons is increased during the period of maximal hyperalgesia that accompanies peripheral inflammation. Changes in the mRNA for CGRP suggest that the increase in spinal content of iCGRP is due to an increase in synthesis of the peptide as the level of mRNA fo r CGRP is increased from 2 to 8 days after injection of CFA. Despite t he decrease in the content of iCGRP in the spinal cord, there is no ap parent decrease in the amount of iCGRP that can be released from the d orsal spinal cord by capsaicin; in fact, capsaicin-evoked release is i ncreased at 4 days. Measurements of the binding of I-125-labelled CGRP in the dorsal spinal cord indicate that high affinity binding sites f or CGRP are downregulated at 4 days after injection of CFA. In total, these data support the hypothesis that the activity of CGRP-containing primary afferent neurons is increased during peripheral inflammation. CGRP released from primary afferent neurons in the spinal cord may co ntribute to cellular changes that accompany peripheral inflammation.