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

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Abstract
1 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. 2 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%. 3 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. 4 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. 5 Intra-arterial infusion of substance P (threshold dose 5 × 10−13mol/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. 6 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.