Aa. Romanovsky et al., PERIPHERAL NALOXONE ATTENUATES LIPOPOLYSACCHARIDE FEVER IN GUINEA-PIGS BY AN ACTION OUTSIDE THE BLOOD-BRAIN-BARRIER, The American journal of physiology, 266(6), 1994, pp. 180001824-180001831
We have previously shown that the febrile response of guinea pigs to l
ipopolysaccharide (LPS) is attenuated by the subcutaneous administrati
on of the tertiary mu-receptor opioid antagonist naloxone-hydrochlorid
e (Nal-HCl). Because Nal-HCl readily crosses the blood-brain barrier (
BBB), this study was undertaken to investigate whether its effect on f
ever is mediated peripherally or centrally. For this, the effects of 1
) Nal-HCl (23 and 46 mu mol/kg sc), 2) the quaternary opioid antagonis
ts Nal-methiodide (Nal-mI, 46 and 92 mu mol/kg sc) and Nal-methobromid
e (Nal-mBr, 92 mu mol/kg sc), which do not cross the BBB, and 3) intra
cerebroventricular Nal-HCl (0.25 and 1.25 mu mol) on the febrile respo
nse to intravenous S. enteritidis LPS (2 mu g/kg) were investigated in
conscious guinea pigs. Under afebrile conditions, both Nal-HCl (wheth
er administered sc or icv) and its quaternary analogues induced hypoth
ermic responses. Peripheral Nal-HCl, Nal-mI, and Nal-mBr also attenuat
ed both phases of the characteristically biphasic LPS fever. The therm
al effects of the peripheral opioid antagonists, both tertiary and qua
ternary, were associated with cutaneous vasodilation. Intracerebrovent
ricularly administered Nal-HCl did not evoke any attenuation of fever.
The analysis of the data shows that Nal-HCl possesses three different
thermoregulatory actions: a central hypothermic action, a peripheral
thermolytic action (which is due to, at least partly, cutaneous vasodi
lation), and a peripheral antipyretic action. The latter effect sugges
ts that, in guinea pigs, circulating opioids may have a role in fever
production.