Neurogenic plasma extravasation in response to mechanical, chemical and thermal stimuli

Nociceptors at distal terminals of unmyelinated primary afferent nerve fibres mediate neurogenic inflammation. Most studies have examined only the neurogenic inflammatory response to non-physiological antidromic electrical nerve stimulation. It has not been possible to determine whether polymodal nociceptors mediate the response to physiological stimulation with mechanical, chemical and thermal stimuli. In this study we have induced plasma protein extravasation to stimulation with wool fabric (81 +/- 9 micrograms/mL), bradykinin (86 +/- 8 micrograms/mL) and heat (111 +/- 16 micrograms/mL) in perfused vacuum-induced blisters on the rat hind footpad. These values represent significant increases over the protein concentration of 30 micrograms/mL (p less than 0.005; p less than 0.001; p less than 0.001, respectively; n = 6 to 8 for each group). Plasma extravasation was significantly reduced for each stimulus modality (p less than 0.001; p less than 0.05; p less than 0.01, respectively) in animals pretreated as neonates with capsaicin, demonstrating that part of the response is neurogenically mediated. It is concluded that neurogenic inflammation to polymodal physiological stimuli occurs in the rat through capsaicin-sensitive primary afferent nerve fibres.