Enhanced antinociception by intrathecally-administered morphine in histamine H₁ receptor gene knockout mice

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• 作者：Mobarakeh ; Jalal Izadi ; Sakurada ; Shinobu ; Hayashi ; Takafumi ; Orito ; Tohru ; Okuyama ; Kaori ; et. al.
• 关键词：Antinociception ; Morphine ; Histamine H₁ receptors ; Knockout mice ; Intrathecal injection ; Histamine H₁ antagonist
• 刊名：Neuropharmacology
• 出版年：2002
• 出版时间：June, 2002
• 年：2002
• 卷：42
• 期：8
• 页码：1079-1088
• 全文大小：294 K

文摘

We previously reported that histamine H₁ 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 H₁ 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 H₁ receptor-mediated suppression of morphine-induced antinociception. These results suggest that existing H₁ receptors play an inhibitory role in morphine-induced antinociception at the spinal cord level.