RELEASE OF SOMATOSTATIN AND ITS ROLE IN THE MEDIATION OF THE ANTIINFLAMMATORY EFFECT INDUCED BY ANTIDROMIC STIMULATION OF SENSORY FIBERS OFRAT SCIATIC-NERVE

1 The effect of antidromic stimulation of the sensory fibres of the sc iatic nerve on inflammatory plasma extravasation in various tissues an d on cutaneous vasodilatation elicited in distant parts of the body wa s investigated in rats pretreated with guanethidine (8 mg kg(-1), i.p. ) and pipecuronium (200 mu g kg(-1), i.v.). 2 Antidromic sciatic nerve stimulation with C-fibre strength (20 V, 0.5 ms) at 5 Hz for 5 min el icited 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. St imulation at 0.5 Hz for 1 h also evoked local plasma extravasation and inhibited the carrageenin-induced (1%, 100 mu l s.c.) cutaneous infla mmation 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 hind leg but still reduced the carrageenin-induced oedema bg 52.1+/-9.7% in the paw on the contralateral side. 3 Plasma extravasation in the knee joint in response to carrageenin (2%, 200 mu l intra-articular inject ion) 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 t he left vagal nerve (20 V, 1 ms, 8 Hz, 10 min) elicited plasma extrava sation 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 mu g kg(-1), i.v.). These respons es were inhibited by 37.8+/-5.1%, 49.7+/-9.9% and 37.6+/-4.2%, respect ively by antidromic sciatic nerve excitation (5 Hz, 5 min) applied 5 m in earlier. 5 Pretreatment with polyclonal somatostatin antiserum (0.5 ml/rat, i.v.) or the selective somatostatin depleting agent cysteamin e (280 mg kg(-1), s.c.) prevented the anti-inflammatory effect of scia tic 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 respons e to vagal nerve stimulation was also prevented by somatostatin antise rum pretreatment. 6 Cutaneous blood flow assessment by laser Doppler f lowmetry indicated that antidromic vasodilatation induced by sciatic n erve stimulation was not inhibited by excitation of the sciatic nerve of the contralateral leg (1 Hz, 30 min) or by somatostatin (10 mu g/ra t; i.v.) injection. 7 Plasma levels of somatostatin increased more tha n 4 fold after stimulation of both sciatic nerves (5 Hz: 5 ruin) but t he 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 syste mic anti-inflammatory-effect evoked by stimulating the peripheral stum p of the sciatic nerve.