A subsidiary fever center in the medullary raphé?

Abstract

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 PGE2in the medullary raphé might contribute to the febrile response, we tested whether direct injections of PGE2into 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. PGE2injections (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 PGE2injected 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.