Vasoactive intestinal polypeptide increases in areas of the dorsal horn of the spinal cord from which other neuropeptides are depleted following peripheral axotomy

Abstract

Peripheral nerve section or local capsaicin application produces depletion of substance P and an enzymatic marker, fluoride-resistant acid phosphatase (FRAP), from circumscribed regions of the terminal areas in the spinal cord. We have made use of this phenomenon to map the extent of central termination of subpopulations of primary afferent neurons containing substance P (SP), somatostatin (SOM), cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP) and FRAP in the rat lumbar spinal cord following sciatic nerve section at midthigh level under ether anaesthesia. Between 2 days and 1 year postoperatively, the animals were perfused transcardially and SP, CCK, VIP and SOM were localised in frozen transverse sections of spinal cord segments L1 to S2 and their corresponding ganglia using unlabelled antibody immunohistochemistry. FRAP was localised using a modified Gomori method. SP, SOM, CCK and FRAP were maximally depleted from identical restricted areas of the dorsal horn of the third, fourth and fifth lumbar segments fifteen days after nerve section and remained so for a year. In contrast, VIP staining increased dramatically in the areas from which the other markers were depleted and showed the same time course. Moreover, a large number of neurons in the corresponding ganglia showed positive VIP immunoreactivity after axotomy but were absent from the unoperated side.