Pro- and anti-inflammatory actions of ricinoleic acid: similarities and differences with capsaicin

We have investigated the pro- and anti-inflammatory effects of ricinoleic a cid (RA), the main active principle of castor oil, in an experimental model of blepharitis induced by intradermal injection of carrageenan in the guin ea-pig eyelid and its possible capsaicin-like mode of action on acutely dis sociated rat dorsal root ganglia (DRG) neurons in vitro. Topical treatment with RA (10-100 mg/guinea-pig) or capsaicin (1-10 mg/guin ea-pig) caused eyelid reddening and oedema. At lower doses (0.3-3 mg/guinea -pig and 0.009-0.09 mg/guinea-pig for RA and capsaicin, respectively) both drugs significantly potentiated the eyelid oedema induced by carrageenan. T he tachykinin NK1 receptor antagonist FK 888 (0.59 mg/kg s.c.) abolished th e potentiation of carrageenan- induced eyelid oedema induced by either RA o r capsaicin. The neutral endopeptidase inhibitor, thiorphan (1.3 mg/kg i.v. ) significantly enhanced the potentiation of carrageenan-induced eyelid oed ema produced by RA. This potentiating effect was abolished by FK 888. Repea ted (8 days) topical application of RA (0.9 mg/guinea-pig) or capsaicin (0. 09 mg/guinea-pig) inhibited the carrageenan-induced eyelid oedema. This ant iinflammatory effect was accompanied by a reduction (75%80% of SP and 46%-5 1 % of NKA) in tachykinin content of the eyelids, as determined by radioimm unoassay. In dissociated rat DRG neurons, RA (0.1 mM for 5 min) significant ly inhibited the inward currents induced by application of capsaicin (I muM ) and/or low pH (5.8), without inducing any currents by itself or changing voltage-dependent currents. Moreover, after 24-h incubation, RA (0.1 mM) si gnificantly decreased the capsaicin (1 muM)-induced calcitonin gene-related peptide (CGRP) release from rat DRG neurons, whereas acute drug superfusio n did not evoke CGRP release by itself. Summarizing, RA possesses capsaicin-like dual proinflammatory and anti-infl ammatory properties which are observed upon acute and repeated application, respectively. However, unlike capsaicin, RA does not induce inward current in DRG neurons and it is devoid of algesic properties in vivo.