Regulation of substance P levels and release in the dorsal horn during nociception

Abstract

A series of experiments was· undertaken in order to address the regulation of substance P ( SP) levels and release in pri~ry afferent neurons during nociception. It was hypothesized that small diameter primary afferent neurons regulate increases in SP levels and release in the dorsal horn during nociceptor activation. It was found that the injection of formalin into the hindpaw or systemic administration of morphine increased immunohistochemical SP-like immunoreactivity ( SPLI) in the dorsal horn after one hour. The time course of formalin-induced SPLI changes was also determined. The injection of saline caused an.increase in dorsal horn SPLI lasting 20 minutes. Formalin produced a biphasic response with early ( 0-10 win) and late ( 20-60 min) increases in SPLI. Naloxone blocked the late increase in SPLI due to formalin only if it was administered prior to hindpaw treatment. Push-pull perfusion was used to measure the rele~se of SPLI into the superficial dorsal horn. Mechanical pinch applied to the hindpaw produced a graded stimulus-response, with noxious intensities of pinch producing SPLI'release. Formalin produced a biphasic effect with decreases in dorsal horn SPLI -release 0-40 minutes and after 60 minutes following hindpaw treatment. The application of a nociceptive pinch to normal and formalin injected animals produced markedly different patterns of SPLI release. The SPLI contents of dorsal horn, dorsal root, and dorsal root ganglion were measured following similar treatments using tissue extraction/ radioimmunoas·say. Formalin injection produced increased dorsal horn SPLI at 20 and 80 minutes. Formalin also increased- dorsal root ganglion SPLI 80 minutes after hindpaw treatment. Noxious pinch slightly decreased dorsal horn and root SPLI. Dorsal root SPLI was unchanged by any other treatment. Saline injection also increased dorsal horn SPLI at 60 minutes. These data show tha-t· both the synthesis and release of SP may influence primary afferent SPLI content, and that acute and subchroriic nociceptor activation produce different patterns of SP release and synthesis in the primary afferent neuron. Formalin activates systems which may limit nociceptive transmission, thus raising the issue of the involvement of SP in the transmission of nociceptive information following formalin injection.