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

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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 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 (250 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.

Original languageEnglish
Pages (from-to)916-922
Number of pages7
JournalBritish journal of pharmacology
Volume125
Issue number4
DOIs
Publication statusPublished - Nov 3 1998

Keywords

  • Anti-inflammatory effect
  • Capsaicin-sensitive primary afferent neurone
  • Cysteamine
  • Dextran-oedema
  • Mustard oil
  • Neurogenic inflammation
  • Somatostatin
  • Somatostatin antiserum

ASJC Scopus subject areas

  • Pharmacology

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