一項研究表明,，與女性相比,，男性能夠從包括嗎啡在內(nèi)的鎮(zhèn)痛劑中獲得更多的好處,。利用小鼠進行的新的研究暗示了一種可能的解釋：在一個與疼痛處理有關(guān)的大腦區(qū)域中，雄鼠具有更多的藥物受體,。盡管這套機制在人體中是否適用尚不得而知,，但是研究人員相信，這項研究為探索鎮(zhèn)痛劑性別效應的更多研究畫出了一條底線,。
新研究使用小鼠作為模式動物的部分原因,，是它們在嗎啡的敏感性上表現(xiàn)出了明顯的性別差異，領導這項研究的美國亞特蘭大市佐治亞州立大學的神經(jīng)科學家Anne Murphy這樣解釋,。Murphy說,，例如，在一個標準的實驗室測試中,，雄鼠和雌鼠在8或9秒鐘內(nèi)都會從一個熱探測器上縮回爪子,。然而在注射了一針嗎啡后，雌鼠頂多能再多忍受1到2秒鐘,，而雄鼠居然可以讓爪子在熱探測器上呆上20秒鐘,。
在12月24日出版的《神經(jīng)科學雜志》上，Murphy和同事報告說,，雄鼠中腦導水管周圍灰質(zhì)——之前的試驗表明該大腦區(qū)域可能是像嗎啡這樣的鴉片類藥物的作用位點——的一部分具有更高密度的μ-鴉片受體,。對于雄鼠來說，直接向該區(qū)域注射嗎啡能產(chǎn)生強烈的止痛作用,，但是在雌鼠中卻沒有觀察到這種效應,。當研究人員通過注射一種捆綁在類似于嗎啡的化合物上的毒素殺死具有μ-鴉片受體的神經(jīng)細胞后，嗎啡便在雄鼠體內(nèi)失去了止痛作用,，但這些鎮(zhèn)痛劑對雌鼠依然好使,。Murphy指出，總而言之,，這些發(fā)現(xiàn)表明,，中腦導水管周圍灰質(zhì)中的μ-鴉片受體差異能夠解釋小鼠對嗎啡敏感性的性別差異,。
Murphy說，有朝一日,，對背后的神經(jīng)生物學機制的進一步了解將有助于研制出針對女性的更為有效的止痛藥,。他強調(diào)，人體研究已經(jīng)表明,，嗎啡在女性中止痛作用較小,，并且副作用更大。
紐約城市大學的神經(jīng)科學家Richard Bodnar表示：“這一發(fā)現(xiàn)是一大突破,，它找到了鴉片在動物止痛中存在性別差異的可行的作用機理,。”其他研究人員之前曾懷疑，鴉片受體的數(shù)量及功能在與疼痛有關(guān)的大腦區(qū)域中存在性別差異,，普爾曼市華盛頓州立大學的神經(jīng)科學家Rebecca Craft指出,，“這項工作首次決定性地證明了這種差異”。
新的發(fā)現(xiàn)能否解釋人體中的鴉片敏感性差異呢,？Craft認為：“它們的原理可能是類似的,，但現(xiàn)在就說人類與動物在這一領域的聯(lián)系是多么多么緊密為時尚早。”（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Neuroscience,，doi:10.1523/JNEUROSCI.4123-08.2008,，Dayna R. Loyd，Anne Z. Murphy
Sex Differences in μ-Opioid Receptor Expression in the Rat Midbrain Periaqueductal Gray Are Essential for Eliciting Sex Differences in Morphine Analgesia
Dayna R. Loyd, Xioaya Wang, and Anne Z. Murphy
Neuroscience Institute, Center for Behavioral Neuroscience, Georgia State University, Atlanta, Georgia 30302-4010
Opioid-based narcotics are the most widely prescribed therapeutic agent for the alleviation of persistent pain; however, it is becoming increasingly clear that morphine is significantly less potent in women compared with men. Morphine primarily binds to μ-opioid receptors (MORs), and the periaqueductal gray (PAG) contains a dense population of MOR-expressing neurons. Via its descending projections to the rostral ventromedial medulla and the dorsal horn of the spinal cord, the PAG is considered an essential neural substrate for opioid-based analgesia. We hypothesized that MOR expression in the PAG was sexually dimorphic, and that these sex differences contribute to the observed sex differences in morphine potency. Using immunohistochemistry, we report that males had a significantly higher expression of MOR in the ventrolateral PAG compared with cycling females, whereas the lowest level of expression was observed in proestrus females. CFA-induced inflammatory pain produced thermal hyperalgesia in both males and females that was significantly reversed in males with a microinjection of morphine into the ventrolateral PAG; this effect was significantly greater than that observed in proestrus and estrus females. Selective lesions of MOR-expressing neurons in the ventrolateral PAG resulted in a significant reduction in the effects of systemic morphine in males only, and this reduction was positively correlated with the level of MOR expression in the ventrolateral PAG. Together, these results provide a mechanism for sex differences in morphine potency.
