神経成長因子合成誘導剤 (4-methylcathechol) による Mustard oil 誘発痛覚過敏の増強効果

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Although there is increasing evidence to suggest that nerve growth factor (NGF) is a peripheral mediator to produce facilitated inflammatory pain, the mechanism underlying development of hyperalgesia has not been fully understood. The aim of the present study was to examine whether pharmacological manipulation of NGF content by its inducer, 4-methyl catechol (4MC), modulates pain behavior in relation to spinal glutamate (Glu) release evoked by an injection of mustard-oil (MO) into the rat hind paw. Under halothane anesthesia (2-3%), an intrathecal (i.t.) loop dialysis catheter and drug delivery catheter (PE-10) were implanted in thirty-six Sprague-Dawley rats. Three days later, 50 ul of 20% of MO was injected (s.c.) into the left hind paw. In rats pretreated with either 4MC (1 or 10 mg/kg, i.p.) or combination of 4MC and anti-NGF (s.c. in the MO-injection site) for three days, MO was injected and paw flinching was counted. Dialysate samples were collected periodically in 10 min intervals and analyzed for Glu level by HPLC-ECD. In additional rats, effects of pretreatment with morphine (MOR, 10 ug, i.t.) were examined. In non-treated rats, flinching increased with time after MO injection in association with an increase in CSF-Glu level. MOR completely blocked these changes. Rats pretreated with 4 MC displayed enhanced flinching in a dose dependent fashion, and the CSF-Glu level showed an increase at 10 min with decline to baseline level at 20 min. These effects of 4MC were diminished by a coadministration of anti-NGF. The present study demonstrates that MO-induced hyperalgesia associated with increased glutamate release was enhanced by NGF inducer and that these effects were reversed by anti-NGF, suggesting possible involvement of NGF in development of central sensitization.
九州歯科学会の論文
1998-02-25

神経成長因子合成誘導剤 (4-methylcathechol) による Mustard oil 誘発痛覚過敏の増強効果

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