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系統識別號 U0026-0812200911553891
論文名稱(中文) 辣椒素誘發大白鼠產生急性痛及熱痛過敏現象之性別差異
論文名稱(英文) Sex Differences in Capsaicin-Induced Nocifensive Responses and Thermal Hyperalgesia in Rats
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 94
學期 2
出版年 95
研究生(中文) 呂雨青
研究生(英文) Yu-Ching Lu
電子信箱 vivianlu.rain@yahoo.com.tw
學號 s3691110
學位類別 碩士
語文別 英文
論文頁數 51頁
口試委員 口試委員-游一龍
口試委員-簡基憲
指導教授-吳豐森
中文關鍵字 雌二醇  類固醇  性別差異  辣椒素受體  熱痛覺過敏現象  痛覺反應 
英文關鍵字 Steroids  Capsaicin receptors  Sex differences  Thermal hyperalgesia  Nocifensive response  17-Estradiol 
學科別分類
中文摘要 我們實驗室先前電生理的研究顯示,雄性類固醇睪酮對雄姓大白鼠背根神經節細胞膜上的辣椒素受體所媒介之電流反應,具有稍微的抑制作用,但是雌性類固醇雌二醇對辣椒素受體所媒介的電流反應,卻有很強的促進作用。最近的臨床研究指出,女性較男性較易感覺到辣椒素所引起的痛,我們的發現可合理地解釋此種現象,這可能是因為不同性別的類固醇荷爾蒙對辣椒素受體的活性有不同的調節作用所導致。但是辣椒素所誘發痛覺反應之性別差異是否也可同樣地發生在大白鼠身上,目前則依然不甚清楚。因此在本研究中,我們利用藥理學的方法和動物痛覺行為的測試技術,探討辣椒素在大白鼠所誘發的痛覺反應和熱痛過敏現象是否有性別上的差異及其機制。我們的結果顯示,辣椒素在雌鼠所誘發的痛覺反應較雄鼠為大。此外,將雌鼠兩側卵巢切除六週後,可使辣椒素所誘發的痛覺反應下降至完全與雄鼠相同。重要的是,皮內注射雌二醇可增強去卵巢雌鼠辣椒素所誘發的痛覺反應,但是皮內注射黃體脂酮,則無增強作用。同樣地,皮下注射雌二醇也可增強雄鼠辣椒素所誘發的痛覺反應,且其增強作用呈現劑量依賴反應。辣椒素在大白鼠所誘發的熱痛過敏現象也有性別上的差異,雌鼠較雄鼠為大,發生的時間也較長。此外,雌鼠在經過卵巢切除手術後,與未經過卵巢切除手術之雌鼠比較,辣椒素所誘發的熱痛過敏現象明顯變小、變短。皮內注射補充雌二醇可增強去卵巢雌鼠辣椒素所誘發之熱痛過敏現象,但是皮下注射補充黃體脂酮,則無增強作用。綜合以上結果可知,辣椒素在雌鼠所誘發的痛覺反應和熱痛過敏現象之所以較雄鼠為大,主要是因為雌鼠所含有的雌二醇能與辣椒素受體交互作用,進而增強了辣椒素受體的活性所導致。





英文摘要 Previous studies from our laboratory have demonstrated that the male sex steroid testosterone inhibits slightly, but the female sex steroid 17-estradiol (E2) potentiates dramatically, the capsaicin receptor-mediated current in male rat dorsal root ganglion neurons. These findings, together with recent clinical observation that women experience capsaicin-induced pain as more intense than men do, suggest that sex differences in pain perception result from differential modulation of the capsaicin receptor by different sex steroids. However, it is unclear whether sex differences in capsaicin-induced pain also occur in rats. In the present study, we used pharmacological methods and nociceptive behavioral tests to determine whether there are sex differences in capsaicin-induced nocifensive behaviors and thermal hyperalgesia in rats in vivo and to explore the mechanism underlying these sex differences. Our results revealed that the capsaicin-induced nocifensive response was significantly greater in female rats than in male rats. Moreover, the enhanced female sensitivity to the capsaicin-induced nocifensive response was completely reversed by ovariectomy (OVX) operated 6 weeks prior to capsaicin injection. Importantly, intradermal injection of E2, but not progesterone potentiated the capsaicin-induced nocifensive response in OVX rats. Similarly, E2 intradermally injected into male rat handpaws dose-dependently enhanced the capsaicin-induced nocifensive response. Sex difference also occurs in capsaicin-induced thermal hyperalgesia, with female rats being greater and longer than male rats. Furthermore, in female rats, capsaicin induced lesser and shorter heat hyperalgesia after OVX compared to sham surgery. In addition, E2 but not progesterone replacement reversed attenuation of capsaicin-induced thermal hyperalgesia in OVX rats. Together, these results suggest that E2 mediates the enhanced sensitivity in female rats to capsaicin-induced nociception and thermal hyperalgesia, consistent with an interaction between E2 and capsaicin receptors in modifying pain perception.





論文目次 Table of Contents…………………………………….….……………...............II
List of Figures ………………………………………..….....….…..............IV
Abstract in Chinese………………………………………………................……1
Abstract…………………………………………………........……….............…2
Introduction…………………………………………………...……….............….4
Capsaicin, TRPV1, and nociception……………………...........…..........4
Modulation of the TRPV1-mediated current by neurosteroids…….........…5
Modulation of capsaicin-induced nociception by neurosteroids............6
Rationale and specific aims of this study………………………...........…7
Materials and Methods……………………………………….….....................9
Animals………………………………………………….…...………..................9
Estrous cycle determination…………………………………......................9
Bilateral ovariectomy……………………..……………...………................10
Capsaicin test……………………………………….……..……...............…..10
Plantar test……………………………………………………………................10
Drugs and Chemicals……………………………………………...............…....11
Statistical analysis………………………………….……….…..................12
Experiment design……………………………………….......….............…...12
Results…………………………………………………...…………..................16
Time course of the capsaicin-induced nocifensive response in rats….......16
Sex difference in the capsaicin-induced nocifensive response in rats......16
Role of female sex steroids in the female enhanced sensitivity to the capsaicin-induced nocifensive response.....………...........….…….......17
Intradermal injection of E2 dose-dependently potentiates the capsaicin-
induced nocifensive response in male rats…………………….....…......…..18
Sex difference in capsaicin-induced thermal hyperalgesia in rat….........19
Role of female sex steroids in the female enhanced sensitivity to capsaicin-induced thermal hyperalgesia……................………...….........…....20
Discussion…………………...………………………..…….………................22
Sex differences in capsaicin-induced nociception and thermal hyperalgesia in rats….…...………………………………...................................….22
E2 mediates the enhanced sensitivities in female rats to capsaicin-
induced nociception and thermal hyperalgsia….……..…..............…....24
Mechanism of interaction between E2 and TRPV1…...........................26
Conclusion…….…..………..............………...….………....…...…...….27
References…………………………………………...…………...............………41
About the author…………………………………….……..............….………..51
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