Release of somatostatin and its role in the mediation of the anti‐inflammatory effect induced by antidromic stimulation of sensory fibres of rat sciatic nerve

1 The effect of antidromic stimulation of the sensory fibres of the sciatic nerve on inflammatory plasma extravasation in various tissues and on cutaneous vasodilatation elicited in distant parts of the body was investigated in rats pretreated with guanethidine (8 mg kg −1 , i.p.) and pipecuronium (200 μg kg −1 , i.v.). 2 Antidromic sciatic nerve stimulation with C‐fibre strength (20 V, 0.5 ms) at 5 Hz for 5 min elicited neurogenic inflammation in the innervated area and inhibited by 50.3±4.67% the development of a subsequent plasma extravasation in response to similar stimulation of the contralateral sciatic nerve. Stimulation at 0.5 Hz for 1 h also evoked local plasma extravasation and inhibited the carrageenin‐induced (1%, 100 μl s.c.) cutaneous inflammation by 38.5±10.0% in the contralateral paw. Excitation at 0.1 Hz for 4 h elicited no local plasma extravasation in the stimulated hindleg but still reduced the carrageenin‐induced oedema by 52.1±9.7% in the paw on the contralateral side. 3 Plasma extravasation in the knee joint in response to carrageenin (2%, 200 μl intra‐articular injection) was diminished by 46.1±12.69% and 40.9±4.93% when the sciatic nerve was stimulated in the contralateral leg at 0.5 Hz for 1 h or 0.1 Hz for 4 h, respectively. 4 Stimulation of the peripheral stump of the left vagal nerve (20 V, 1 ms, 8 Hz, 10 min) elicited plasma extravasation in the trachea, oesophagus and mediastinal connective tissue in rats pretreated with atropine (2 mg kg −1 , i.v.), guanethidine (8 mg kg −1 , i.p.) and pipecuronium (200 μg kg −1 , i.v.). These responses were inhibited by 37.8±5.1%, 49.7±9.9% and 37.6±4.2%, respectively by antidromic sciatic nerve excitation (5 Hz, 5 min) applied 5 min earlier. 5 Pretreatment with polyclonal somatostatin antiserum (0.5 ml/rat, i.v.) or the selective somatostatin depleting agent cysteamine (280 mg kg −1 , s.c.) prevented the anti‐inflammatory effect of sciatic nerve stimulation (5 Hz, 5 min) on a subsequent neurogenic plasma extravasation of the contralateral paw skin. The inhibitory effect of antidromic sciatic nerve excitation on plasma extravasation in response to vagal nerve stimulation was also prevented by somatostatin antiserum pretreatment. 6 Cutaneous blood flow assessment by laser Doppler flowmetry indicated that antidromic vasodilatation induced by sciatic nerve stimulation was not inhibited by excitation of the sciatic nerve of the contralateral leg (1 Hz, 30 min) or by somatostatin (10 μg/rat, i.v.) injection. 7 Plasma levels of somatostatin increased more than 4 fold after stimulation of both sciatic nerves (5 Hz, 5 min) but the stimulus‐evoked increase was not observed in cysteamine (280 mg kg −1 , s.c.) pretreated rats. 8 These results suggest that somatostatin released from the activated sensory nerve terminals mediates the systemic anti‐inflammatory effect evoked by stimulating the peripheral stump of the sciatic nerve.British Journal of Pharmacology (1998) 123 , 936–942; doi: 10.1038/sj.bjp.0701685