Effects of spinal lesions on substance P levels in the rat sympathetic preganglionic cell column: Evidence for local spinal regulation

Abstract

Substance P has been localized to the neuropil of sympathetic preganglionic neurons in light and electron microscopic studies. Two recent reports have suggested that the majority of substance P in the rat intermediolateral cell column was contained in synaptic terminals of bulbospinal axons. However, previous investigations in our laboratory indicated the presence of major substance P spinal-sympathetic preganglionic neuron circuitry in pigeon. The present study used radioimmunoassay and immunohistochemistry to examine substance P levels in rat intermediolateral cell column following various spinal lesions in order to assess the relative contributions of bulbospinal and intraspinal substance P neurons to the substance P content of the intermediolateral cell column. The results from these experiments support the existence of both bulbospinal and intraspinal substance P-containing projections to the rat intermediolateral cell column. In addition, characterization of spinal cord substance P-like immunoreactivity by combined high performance liquid chromatography and radioimmunoassay, revealed that substance P in rat intermediolateral cell column was indistinguishable from synthetic substance P. Following transection of thoracic spinal cord, substance P-immunoreactive staining was still evident in the intermediolateral cell column caudal to the lesion. These substance P-positive fibers were studded with bouton-like swellings and appeared normal. Following high cervical hemisection, depletion of substance P (radioimmunoassay measurements) was bilateral and equal in the intermediolateral cell column: 25%, depletion was observed after 7 days and 35% depletion after 14 days. However, rats which were hemisected at low cervical and/or mid-thoracic levels contained normal or elevated amounts of substance P in the intermediolateral cell column. Since substance P remains in the intermediolateral cell column following total transection, substance P spinal-sympathetic preganglionic neuron circuitry must exist. Additionally, depletion of substance P following high cervical hemisection suggests the existence of a substance P-containing, bilateral bulbospinal pathway to the intermediolateral cell column. The observation that substance P levels were normal or elevated following low cervical lesions raises the possibility that intraspinal substance P neurons can compensate for loss of substance P in the spinal cord. Sprouting or altered substance P metabolism and/or release by intraspinal substance P neurons could be responsible, suggesting an important homeostatic mechanism for maintaining substance P content within the intermediolateral cell column.