Capsaicin pretreatment attenuates LPS-induced hypothermia through TRPV1-independent mechanisms in chicken.

It has been demonstrated that chicken TRPV1 (transient receptor potential vanilloid of subtype-1) is insensitive to capsaicin (CAP), and therefore, a chicken model is suitable to analyze the CAP-sensitive TRPV1-independent pathway. We elucidated here the possible involvement of the pathway in hypothermia induced by bacterial endotoxin (lipopolysaccharide, LPS) in chickens. Chicks were pretreated with CAP (10 mg/kg, iv) at 1, 2 and 3 days of age to desensitize them towards the CAP-sensitive pathway. An intravenous injection of LPS in 4-day-old chicks caused progressive hypothermia, ending with collapse and 78% mortality within 12 h after injection. The CAP pretreatment rescued the LPS-induced endotoxin shock and hypothermia in chicks. LPS-induced iNOS expression as well as NO production in liver and lung was suppressed by CAP pretreatment. CAP pretreatment also attenuated hypothermia due to exposure of chicks to cold ambient temperature. These findings suggest that a CAP-sensitive TRPV1-independent pathway may be involved in pathophysiological hypothermic reactions through the mediation of NO in chickens.

Involvement of a capsaicin-sensitive TRPV1-independent mechanism in lipopolysaccharide-induced fever in chickens.

It has been demonstrated that capsaicin blocks lipopolysaccharide (LPS)-induced fever in mammals. In this study, we investigated TRPV1 (transient receptor potential ion channel of vanilloid subtype-1)-independent action of capsaicin on LPS-induced fever in chickens. The chicken is a valuable model for this purpose because chicken TRPV1 has been shown to be insensitive to capsaicin and thus the effects of capsaicin can be attributed to TRPV1-independent mechanisms. Administration of capsaicin (10 mg/kg, iv) to conscious unrestrained chicks at 5 days of age caused a transient decrease in body temperature. This effect of capsaicin was not observed in chicks that had been pretreated twice with capsaicin, indicating that the capsaicin-sensitive pathway can be desensitized. LPS (2 mg/kg, ip) induced fever that lasted for about 2.5 h, but fever was not induced in chicks that had been pretreated with capsaicin for 2 days. The preventive effect of capsaicin on LPS-induced fever was not blocked by capsazepine, an antagonist for TRPV1, but the antagonist per se blocked the febrile response to LPS. These findings suggest that a capsaicin-sensitive TRPV1-independent mechanism may be involved in LPS-induced fever.