Prostanoids in the preoptic hypothalamus mediate systemic lipopolysaccharide-induced hyperalgesia in rats

Michie Abe, Takakazu Oka, Tetsuro Hori, Shosuke Takahashi

Research output: Contribution to journalArticle

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Abstract

The systemic administration of lipopolysaccharide (LPS), an experimental model of systemic bacterial infection is known to modulate nociception. It increases the prostaglandin E 2 (PGE 2 ) levels in the preoptic area of the hypothalamus (POA) and the microinjection of PGE 2 into the POA and the neighboring basal forebrain induces hyperalgesia. We, therefore, hypothesized that the PGE 2 synthesized in these regions mediates intravenous (i.v.) LPS-induced hyperalgesia. To test this hypothesis, we microinjected cyclooxygenase (COX) inhibitors into several sites in the rat hypothalamus and observed their effects on the LPS (0.1-100 μg/kg, i.v.)-induced changes in nociceptive behavior as assessed by a plantar test. LPS (10 and 100 μg/kg, i.v.) reduced the paw-withdrawal latency at 90 min and 45-60 min after injection, respectively, both thus indicating a hyperalgesic effect. This hyperalgesia was observed only in the period before the development of fever which started 120-135 min after the LPS injection. The LPS (100 μg/kg, i.v.)-induced hyperalgesia was completely abolished by pretreatment with the microinjection of diclofenac (an inhibitor of COX-1 and 2) at 1.0 ng into the bilateral POA. Furthermore, it was also blocked by the microinjection of NS-398 (a selective COX-2 inhibitor) at 1.0 ng into the bilateral POA and the horizontal limb of the diagonal band of Broca (DBB), but not the lateral hypothalamic area, the paraventricular hypothalamic nucleus, and the ventromedial hypothalamic nucleus. These findings suggest that LPS (i.v.)-induced hyperalgesia is mediated predominantly through a COX-2 induced prostanoids in the POA and the DBB in rats.

Original languageEnglish
Pages (from-to)41-49
Number of pages9
JournalBrain Research
Volume916
Issue number1-2
DOIs
Publication statusPublished - Oct 19 2001

Fingerprint

Hyperalgesia
Hypothalamus
Prostaglandins
Lipopolysaccharides
Preoptic Area
Microinjections
Prostaglandins E
Diagonal Band of Broca
Cyclooxygenase 2
Ventromedial Hypothalamic Nucleus
Lateral Hypothalamic Area
Cyclooxygenase 1
Injections
Nociception
Cyclooxygenase Inhibitors
Paraventricular Hypothalamic Nucleus
Diclofenac
Cyclooxygenase 2 Inhibitors
Bacterial Infections
Fever

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Prostanoids in the preoptic hypothalamus mediate systemic lipopolysaccharide-induced hyperalgesia in rats. / Abe, Michie; Oka, Takakazu; Hori, Tetsuro; Takahashi, Shosuke.

In: Brain Research, Vol. 916, No. 1-2, 19.10.2001, p. 41-49.

Research output: Contribution to journalArticle

Abe, Michie ; Oka, Takakazu ; Hori, Tetsuro ; Takahashi, Shosuke. / Prostanoids in the preoptic hypothalamus mediate systemic lipopolysaccharide-induced hyperalgesia in rats. In: Brain Research. 2001 ; Vol. 916, No. 1-2. pp. 41-49.
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