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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/R411    most recent 00465.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Fraga, D. Articles by Zampronio, A. R. PubMed PubMed Citation Articles by Fraga, D. Articles by Zampronio, A. R.

INFLAMMATION AND CYTOKINES

Endogenous opioids: role in prostaglandin-dependent and -independent fever

¹Department of Pharmacology and ³Department of Physiology, Biological Sciences Section, Federal University of Paraná, Curitiba, Paraná, Brazil; and ²Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

Submitted 29 June 2007 ; accepted in final form 13 November 2007

This study evaluated the participation of µ-opioid-receptor activation in body temperature (T_b) during normal and febrile conditions (including activation of heat conservation mechanisms) and in different pathways of LPS-induced fever. The intracerebroventricular treatment of male Wistar rats with the selective opioid µ-receptor-antagonist cyclic D-Phe-Cys-Try-D-Trp-Arg-Thr-Pen-Thr-NH₂ (CTAP; 0.1–1.0 µg) reduced fever induced by LPS (5.0 µg/kg) but did not change T_b at ambient temperatures of either 20°C or 28°C. The subcutaneous, intracerebroventricular, and intrahypothalamic injection of morphine (1.0–10.0 mg/kg, 3.0–30.0 µg, and 1–100 ng, respectively) produced a dose-dependent increase in T_b. Intracerebroventricular morphine also produced a peripheral vasoconstriction. Both effects were abolished by CTAP. CTAP (1.0 µg icv) reduced the fever induced by intracerebroventricular administration of TNF- (250 ng), IL-6 (300 ng), CRF (2.5 µg), endothelin-1 (1.0 pmol), and macrophage inflammatory protein (500 pg) and the first phase of the fever induced by PGF₂ (500.0 ng) but not the fever induced by IL-1β (3.12 ng) or PGE₂ (125.0 ng) or the second phase of the fever induced by PGF₂. Morphine-induced fever was not modified by the cyclooxygenase (COX) inhibitor indomethacin (2.0 mg/kg). In addition, morphine injection did not induce the expression of COX-2 in the hypothalamus, and CTAP did not modify PGE₂ levels in cerebrospinal fluid or COX-2 expression in the hypothalamus after LPS injection. In conclusion, our results suggest that LPS and endogenous pyrogens (except IL-1β and prostaglandins) recruit the opioid system to cause a µ-receptor-mediated fever.

prostaglandin independent; body temperature; morphine; CTAP