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Physiology and Pharmacology of Temperature Regulation

A subsidiary fever center in the medullary raphé?

Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia

Submitted 25 February 2005 ; accepted in final form 16 June 2005

In fever, as in normal thermoregulation, signals from the preoptic area drive both cutaneous vasoconstriction and thermogenesis by brown adipose tissue (BAT). Both of these responses are mediated by sympathetic nerves whose premotor neurons are located in the medullary raphé. EP3 receptors, key prostaglandin E₂ (PGE₂) receptors responsible for fever induction, are expressed in this same medullary raphé region. To investigate whether PGE₂ in the medullary raphé might contribute to the febrile response, we tested whether direct injections of PGE₂ into the medullary raphé could drive sympathetic nerve activity (SNA) to BAT and cutaneous (tail) vessels in anesthetized rats. Microinjections of glutamate (50 mM, 60–180 nl) into the medullary raphé activated both tail and BAT SNA, as did cooling the trunk skin. PGE₂ injections (150–500 ng in 300–1,000 nl) into the medullary raphé had no effect on tail SNA, BAT SNA, body temperature, or heart rate. By contrast, 150 ng PGE₂ injected into the preoptic area caused large increases in both tail and BAT SNA (+60 ± 17 spikes/15 s and 1,591 ± 150% of control, respectively), increased body temperature (+1.8 ± 0.2°C), blood pressure (+17 ± 2 mmHg), and heart rate (+124 ± 19 beats/min). These results suggest that despite expression of EP3 receptors, neurons in the medullary raphé are unable to drive febrile responses of tail and BAT SNA independently of the preoptic area. Rather, they appear merely to transmit signals for heat production and heat conservation originating from the preoptic area.

prostaglandin E₂; febrile responses; sympathetic activation; tail; brown adipose tissue

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