Substance P induces chemotaxis of neutrophils in normal and capsaicin‐treated rats

Primary afferent unmyelinated nerves modulate the inflammatory response to injury through a process known as neurogenic inflammation. The undecapeptide Substance P is contained in many of these nerves and therefore may be an important mediator of the response. Treatment of neonatal rats with capsaicin permanently destroys primary afferent unmyelinated nerves and depletes the skin and other organs of Substance P. These animals have a reduced capacity to mount an inflammatory response to injury. We examined the ability of Substance P to chemo-attract neutrophils from normal rats and rats treated as neonates with capsaicin. Substance P was shown to cause normal rat neutrophils to chemotact at an optimum concentration of 5 X 10(-5)M. Equivalent chemotaxis was observed in neutrophils from rats pretreated as neonates with capsaicin. Substance P did not increase chemokinesis. These in vitro results support the view that the reduced neurogenic inflammatory response seen in capsaicin-pretreated rats is not due to a direct toxic effect of capsaicin on neutrophils, but may be due to a decreased availability of neurally derived Substance P at the site of injury.