Substance P neurones in medullary baroreflex areas and baroreflex function of capsaicin-treated rats. Comparison with other primary afferent systems

Abstract Adult rats (age 13–17 weeks) treated 20 h after birth with capsaicin (50 mg/kg s.c.) showed a 50% loss of substance P-immunoreactive nerve terminals in the thoracic substantia gelatinosa as revealed by quantitative immunohistochemistry and radioimmunoassay. Other spinal substance P systems were unchanged. A similar decrease of immunoreactive substance P axons and nerve terminals was observed in medullary primary afferent systems, namely in IX and X rootlets, tractus spinalis nervi V, tractus solitarius and substantia gelatinosa nervi V. Other medullary substance P fibres, e.g. in the reticular formation, nucleus motorius nervi X and XII, inferior olive and area postrema, were not obviously changed. The nucleus tractus solitarii receiving, among others, IX and X primary afferents, e.g. from baroreceptors and chemoreceptors, showed a particular pattern of depletion: although the substance P axons penetrating from the tractus solitarius mainly into the intermediate and caudal nucleus tractus solitarii were markedly reduced in capsaicin-treated rats, the total number of substance P nerve terminals in the intermediate and caudal nucleus tractus solitarii was only moderately decreased and appeared normal in the cranial portion of the nucleus. The number of substance P-immunoreactive cells in the nucleus tractus solitarii was unchanged. Radioimmunoassay of substance P levels showed a 60% decrease in the microdissected substantia gelatinosa nervi V, but only insignificant decreases (by 20%) in microdissected divisions of the nucleus tractus solitarii and reticular formation. Thus, capsaicin destroyed a considerable part of primary spinal and medullary substance P afferents. In the entire nucleus tractus solitarii most of substance P is contained in a capsaicin-insensitive, probably intrinsic system. However, the intermediate and caudal divisions contain, in addition, primary afferent IX and X substance P terminals which were partly destroyed by capsaicin. In view of a recent proposal that substance P is the transmitter released from baroreceptor afferents, blood pressure and baroreflex function were measured in capsaicin-treated (50 and up to 600 mg/kg) rats; neither differed from controls. While, at first sight, this finding militates against a transmitter role of substance P in the baroreceptor reflex pathway, incomplete destruction of primary substance P afferents in the nucleus tractus solitarii by capsaicin and the possible development of compensatory mechanisms during growth of the animals have to be considered as alternative explanations. Furthermore, in the same rats, tests on the function of other primary afferents yielded, in part, incongruent results. The threshold for nociceptive chemical stimuli, as determined with capsaicin and formalin, was increased. On the other hand, threshold to nociceptive heat was unchanged in the tail-flick, but increased in the hot plate test.