Evidence for release of calcitonin gene-related peptide and neurokinin a from sensory nerve endings in vivo

Abstract

Sensitive radioimmunoassays for calcitonin gene-related peptide and the tachykinin, neurokinin A, have been used to show that acute administration of the sensory neurotoxin capsaicin (10 mg/kg i.p.) to normal adult rats, causes a substantial release of calcitonin gene-related peptide immunoreactivity (15-fold increase) and neurokinin A immunoreactivity (4- to 5-fold increase) into the plasma. Neonatal administration of capsaicin (50 mg/kg s.c.) produced a long term deficit in the lumbar dorsal root ganglia content of calcitonin gene-related peptide (76% depletion), and neurokinin A immunoreactivity (86% depletion) in rats killed 6 weeks after administration. Acute capsaicin treatment of neonatally capsaicin-treated rats revealed that these animals still showed a capsaicin-evoked release of calcitonin gene-related peptide and neurokinin A immunoreactivity into the plasma. The increase in plasma content was, however, substantially less than that seen in normal (vehicle-treated) rats and was proportional to the initial basal plasma level of the respective peptides. Immunohistochemical staining using an anti-calcitonin gene-related peptide antiserum revealed that, despite the neonatal capsaicin treatment and loss of dorsal root ganglia content, the lumbar dorsal horn had a near normal pattern of calcitonin gene-related peptide immunoreactivity. This observation was supported by radioimmunoassays carried out on lumbar dorsal horn samples obtained from the same rats, which showed no significant decrease in calcitonin gene-related peptide immunoreactivity, whilst the dorsal horn content of neurokinin A was some 70% below control values. Parallel assays of spinal cord substance P content using an amino-terminal specific substance P antiserum which did not cross-react with neurokinin A showed that, as expected, neonatal capsaicin treatment had produced a loss of > 80% of the substance P content from the dorsal horn.