Enhanced antinociception by intrathecally-administered morphine in histamine H1 receptor gene knockout mice.
We previously reported that histamine H(1) receptor gene knockout mice (H1KO) showed lower spontaneous nociceptive threshold to pain stimuli when compared to wild-type mice. The objective of the present study was to examine the antinociceptive effect of intrathecally-administered morphine in H1KO mice. The antinociceptive effects of morphine were examined using assays for thermal (tail-flick, hot-plate, paw-withdrawal), mechanical (tail-pressure) and chemical nociception (formalin and capsaicin tests) using H1KO and wild-type mice. In these nociceptive assays, intrathecally-administered morphine produced significant antinociceptive effects in wild-type mice. The antinociceptive effect produced by intrathecally administered morphine was enhanced in the knockout mice. We also examined the effect of an histamine H(1) receptor antagonist, an active (d-) isomer of chlorpheniramine, on morphine-induced antinociception in ICR mice. The intrathecal co-administration of d-chlorpheniramine enhanced the effect of morphine in all nociceptive assays examined. The pharmacological experiments using d-chlorpheniramine further substantiate the evidence for the histamine H(1) receptor-mediated suppression of morphine-induced antinociception. These results suggest that existing H(1) receptors play an inhibitory role in morphine-induced antinociception at the spinal cord level.
Department of Pharmacology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-Ku, Sendai 980-8575, Japan.
Jalal Izadi
JI
Mobarakeh
Shinobu
S
Sakurada
Takafumi
T
Hayashi
Tohru
T
Orito
Kaori
K
Okuyama
Tsukasa
T
Sakurada
Atsuo
A
Kuramasu
Takehiko
T
Watanabe
Takeshi
T
Watanabe
Kazuhiko
K
Yanai
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010812:Physical Stimulation; D011969:Receptors, Histamine H1 / Q000172:deficiency* / Q000235:genetics*; D013268:Stimulation, Chemical
D000700:Analgesics; D011969:Receptors, Histamine H1; D002744:Chlorpheniramine; D009020:Morphine