Differential effects of capsaicin on the content of somatostatin,substance P,and neurotensin in the nervous system of the rat

Summary The distribution of immunoreactive substance P (I-SP), somatostatin (I-SRIF), and neurotensin (I-NT) and the effect of capsaicin treatment on the concentration of these peptides was studied in the peripheral and central nervous system of the rat.Neonatal capsaicin treatment (50 mg/kg s.c.) caused a depletion of I-SRIF as well as of I-SP in sensory nerves and in the dorsal half of the spinal cord. No recovery of the peptide content was found when examined 4 months later suggesting an irrerersible effect. I-NT, not a constituent of primary sensory neurons, was not changed in the spinal cord. None of the peptides studied was depleted in the hypothalamus or preoptic area.Capsaicin treatment of adult rats also led to a decrease of I-SRIF and I-SP in primarh sensory neurons. The highest dose used (950 mg/kg s.c.) induced no greater depletion than the lowest one (50 mg/kg), except for I-SP in dorsal root ganglia. Intraperitoneal injection of capsaicin led to a higher degree of depletion than subcutaneous administration as examined 1 week after treatment. In contrast to neonatal treatment, the I-SRIF content was completely restored within 4 months after treatment of adult rats. The I-SP content, however, did not completely recover in all areas but remained reduced in cornea, vagus nerve, dorsal spinal cord, and medulla oblongata for up to 9 months.Intraventricular administration of capsaicin (200 g) caused a depletion of I-SP in the medulla oblongata but had no effect on the content of all 3 peptides in hypothalamus or preoptic area. In contrast to systemic treatment, no depletion of I-SP or I-SRIF was found in the trigeminal ganglion. Chemosensitivity of the eye was abolished after intraventricular or systemic treatment. Repeated topical application of a capsaicin solution (10 mg/ml) to the eye led within 4 h to a nearly complete depletion of I-SP in the cornea.These experiments show that capsaicin treatment of rats caused a depletion of both I-SRIF and I-SP in primary sensory neurons. While topical or systemic capsaicin administration causes depletion in terminals, the failure of intraventricular injections of capsaicin to deplete the peptides in the trigeminal ganglion suggests that depletion of the entire neuron requires an action of capsaicin on the peripheral branch and/or the cell body.