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

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 μg ml −1 in 50 μl, 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 μg 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.British Journal of Pharmacology (1998) 125 , 916–922; doi: 10.1038/sj.bjp.0702144