Systemic anti-inflammatory effect induced by counter-irritation through a local release of somatostatin from nociceptors

Abstract

1. Neurogenic plasma extravasation evoked by topical application of 1% vv(-1) mustard oil on the skin of the acutely denervated rat hindleg (primary reaction) inhibited the development of a subsequent oil-induced plasma extravasation induced in the skin of the contralateral hindleg by 49.3+/-7.06% (n=9) and in the conjunctival mucosa due to 0.1% wv(-1) capsaicin instillation by 33.5+/-10.05% (n=6). The primary reaction also inhibited the non-neurogenic hindpaw oedema evoked by s.c. injection of 5% wv(-1) dextran into the chronically denervated hindpaw by 48.0+/-4.6% (n= 5). 2. Capsaicin injection (100 microg ml(-1) in 50 microl, s.c.) into the acutely denervated hindleg caused 56.5+/-4.0% (n=5) inhibition in the intensity of plasma extravasation elicited by 1% vv(-1) mustard oil smearing on the contralateral side. After chronic denervation, subplantar injection of 5% wv(-1) dextran elicited a non-neurogenic inflammatory response with intensive tissue oedema without causing any systemic anti-inflammatory effect. Bilateral adrenalectomy did not inhibit the mustard oil-induced anti-inflammatory effect in the contralateral hindleg. 3. Pretreating the rats with polyclonal somatostatin antiserum (0.5 ml rat(-1), i.v.) or with the somatostatin depleting agent cysteamine (280 mg kg(-1), s.c.) prevented the inhibitory action of mustard oil-induced inflammation on subsequent neurogenic plasma extravasation and strongly diminished the inhibition of non-neurogenic oedema formation evoked by dextran. 4. Exogenous somatostatin (10 microg kg(-1), i.p.) caused a 30.3+/-8.3% (n=6) inhibition of plasma extravasation caused by mustard oil smearing on the acutely denervated hindleg and this inhibitory effect was abolished by somatostatin antiserum (0.5 ml rat(-1), i.v.). The plasma level of somatostatin-like immunoreactivity (SST-LI) increased by 40.03+/-6.8% (n= 6) 10 min after topical application of 1% vv(-1) mustard oil on the acutely denervated hindpaws compared to the paraffin oil treated control group. Chronic denervation of the hindlegs or cysteamine (280 mg kg(-1), s.c.) pretreatment prevented the mustard oil-induced elevation of SST-LI in plasma. 5. It is concluded that chemical excitation of the capsaicin-sensitive sensory receptors not only induces local neurogenic plasma extravasation but also inhibits the development of a subsequent inflammatory reaction at remote sites of the body in the rat. A role for somatostatin in this systemic anti-inflammatory effect is suggested.