Mechanism of hyperalgesia in SART stressed (repeated cold stress) mice: antinociceptive effect of neurotropin.
Exposing mice to 24 and 4 degrees C in alternate 1 hr periods in the day time and maintaining 4 degrees C at night for several days decreases the tail clamp pressure required to evoke pain behavior. This model is referred to as SART (specific alternation rhythm of temperature) stress. An extract from inflamed skin of rabbits inoculated with vaccinia virus (neurotropin) clearly normalized the hyperalgesia in this SART stress model. To clarify the mechanism of the hyperalgesia in SART mice and the mode of the antinociceptive action of neurotropin in this model, the influence of systemically administered neurotransmitter related drugs was studied. 1) Neurotropin, 5-hydroxytryptophan and L-dihydroxyphenylalanine significantly normalized the decrease in nociceptive threshold, and muscimol tended to inhibit it in nociceptive threshold in SART stressed mice. 2) Haloperidol, phenoxybenzamine, reserpine, bicuculline, scopolamine, physostigmine and naloxone alone did not influence the nociceptive threshold in SART stressed mice. 3) The antinociceptive effect of neurotropin was significantly attenuated by p-chlorophenylalanine, haloperidol and phenoxybenzamine; and it was completely inhibited by reserpine. 4) Naloxone, bicuculline, scopolamine and physostigmine had no influence on the antinociceptive effect of neurotropin. These results suggest that hypofunction mainly of the monoaminergic systems contributes to hyperalgesia in SART stressed mice and that neurotropin produces the antinociceptive effect by restoring these neural functions.
Ohara
H
H
Institute of Bio-Active Science, Nippon Zoki Pharmaceutical Co., Ltd., Hyogo, Japan.
Kawamura
M
M
Namimatsu
A
A
Miura
T
T
Yoneda
R
R
Hata
T
T
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects; D004347:Drug Interactions; D010134:Fenclonine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006930:Hyperalgesia / Q000503:physiopathology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009118:Muscimol / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*
D011134:Polysaccharides; D010643:Phenoxybenzamine; D009118:Muscimol; D007980:Levodopa; C010491:neurotropin; D012110:Reserpine; D006916:5-Hydroxytryptophan; D006220:Haloperidol; D010134:Fenclonine