Regulatory mechanisms for substance P in the dorsal horn during a nociceptive stimulus: axoplasmic transport vs electrical activity.

Substance P (SP) is believed to be a neuromediator of nociception in the dorsal horn of the spinal cord. SP precursor is synthesized in the dorsal root ganglia (DRG) and transported via axoplasmic transport to the nerve terminal where it is stored and released as SP. The chemical nociceptive stimulus, formalin, when injected into the hindpaw causes an increase in the level of SP in the dorsal horn. This increase in SP may be the result of increased electrical activity due to activation of free nerve endings or the transport of some chemical or trophic signal to the DRG or to the central terminal. This study investigates the mechanism of the SP increase during the formalin stimulus. Rats were anesthetized and a laminectomy performed. In some experiments the sciatic nerve was exposed. Agar gel pads containing either colchicine or tetrodotoxin (TTX) were applied to the dorsal root or sciatic nerve prior to the injection of 5% formalin or saline into the hindpaw. Electrical activity across the dorsal root distal to the gel pad was monitored to determine the effects of colchicine and TTX on the nerve. Sixty min after the injection into the hindpaw, the animal was perfused and the lumbar spinal cord removed. Ten-micron frozen sections were stained for SP. It was found that the formalin-evoked increase in SP could be partially blocked by either colchicine or TTX applied to the dorsal root and completely blocked by the application of both agents together. TTX or colchicine applied to the sciatic nerve completely blocked the formalin-evoked increase in SP.(ABSTRACT TRUNCATED AT 250 WORDS)