Central efferent pathways mediating shivering thermogenesis

Abstract

Shivering is a remarkable thermogenic response when body temperature needs to be defended from environmental cold challenges as well as during the development of fever. The preoptic area (POA) receives both environmental thermal information from the skin and pyrogenic signals from the immune system activated by infection and the POA sends descending signals that induce shivering in skeletal muscles. However, the efferent pathway from the POA that is responsible for shivering is unknown. In this study, we examined the involvement of several brain regions in the cooling‐evoked or febrile shivering response in isoflurane‐anesthetized rats. Cooling the trunk skin or nanoinjecting prostaglandin E2 (PGE2) into the POA evoked an increase in the EMG level recorded from the nuchal muscle. Both cooling‐ and PGE2‐evoked EMG increases were blocked by bilateral injections of muscimol, a GABAA receptor agonist, into the dorsomedial hypothalamic nucleus (DMH). In addition, injection of muscimol or 8‐OH‐DPAT, a 5‐HT1A receptor agonist, into the rostral raphe pallidus nucleus (rRPa) also blocked the EMG increase. These results suggest that the DMH and rRPa are essential synaptic integration sites in the efferent neuronal pathway from the POA that mediates the shivering responses to skin cooling and to pyrogens and that this pathway can be modulated by serotonergic inputs to the medullary raphe. Supported by NIH and MEXT Japan.