DECREASE OF SUBSTANCE P IN PRIMARY AFFERENT NEURONES AND IMPAIRMENT OF NEUROGENIC PLASMA EXTRAVASATION BY CAPSAICIN

Abstract

Rats were pretreated with capsaicin (50 mg/kg, s.c.) on the 2nd, 10th, or 20th day of life. Three months later immunoreactive substance P (I‐SP) was determined in skin, sensory nerves and the central nervous system. Neurogenic plasma extravasation was also examined. Pretreatment at the age of 2 or 10 days resulted in a decrease (26 to 69%) of I‐SP in skin, saphenous and vagus nerve, dorsal roots, dorsal half of the spinal cord, and medulla oblongata. The I‐SP content of the ventral half of the spinal cord, of midbrain, hypothalamus, striatum, cortex, and cerebellum remained unchanged. Neurogenic plasma extravasation was inhibited by more than 80%. In contrast to this irreversible effect of capsaicin on newborn rats, pretreatment of 20 day old rats led to reversible depletion of I‐SP and to reversible impairment of neurogenic plasma extravasation. Capsaicin pretreatment of adult rats caused a marked depletion of I‐SP in the skin of the hind paw and an impairment of neurogenic plasma extravasation. A similar decrease of I‐SP was seen after chronic denervation of the skin. Intra‐arterial infusion of substance P (threshold dose 5 × 10−13 mol/min) or physalaemin induced dose‐dependent plasma extravasation. Somatostatin, vasoactive intestinal polypeptide, caerulein and the enkephalin‐analogue FK 33–824 were ineffective in doses 100 fold higher. The results indicate that the action of capsaicin on substance P neurones is restricted to primary sensory neurones. Since in every case a decreased substance P content of the skin was associated with impaired neurogenic plasma extravasation, it is suggested that release of substance P is involved in neurogenic plasma extravasation.