Hypothalamic mechanisms of pain modulatory actions of cytokines and prostaglandin E2

T. Hori, T. Oka, M. Hosoi, M. Abe, K. Oka

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49 Citations (Scopus)


A decrease and subsequent increase in nociceptive threshold in the whole body are clinical symptoms frequently observed during the course of acute systemic infection. These biphasic changes in noeiceptive reactivity are brought about by central signal substances induced by peripheral inflammatory messages. Systemic administration of lipopolysaccharide (LPS) or interleukin-1β (IL-1β), an experimental model of acute infection, may mimic the biphasic changes in nociception, hyperalgesia at small doses of LPS, and IL-1β and analgesia at larger doses. Our behavioral and electrophysiological studies have revealed that IL-1β in the brain induces hyperalgesia through the actions of prostaglandin E2 (PGE2) on EP3 receptors in the preoptic area and its neighboring basal forebrain, whereas the IL-1β-induced analgesia is produced by the actions of PGE2 on EP1 receptors in the ventromedial hypothalamus. An intravenous injection of LPS (10-100 μg/kg) produced hyperalgesia only during the period before fever develops and was abolished by mieroinjection of NS-398 (an inhibitor of cyclooxygenase 2) into the preoptic area, but not into the other areas in the hypothalamus. The hyperalgesia induced by the cytokines PGE2 and LPS may explain the systemic hyperalgesia clinically observed in the early phase of infectious diseases, which probably warns the organisms of infection before the full development of sickness symptoms. The switching of nociception from hyperalgesia to analgesia accompanied by sickness symptoms may reflect changes in the host's strategy for fighting microbial invasion as the disease progresses.

Original languageEnglish
Pages (from-to)106-120
Number of pages15
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • History and Philosophy of Science


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