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系統識別號 U0026-0812200915265272
論文名稱(中文) 睪脂酮在辣椒素誘發大白鼠產生急性痛和熱痛過敏現象之性別差異上所擔任的角色
論文名稱(英文) The Role of Testosterone in 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 97
學期 2
出版年 98
研究生(中文) 王思懿
研究生(英文) Su-Yi Wang
學號 s3695107
學位類別 碩士
語文別 英文
論文頁數 41頁
口試委員 口試委員-簡基憲
指導教授-吳豐森
召集委員-黃阿敏
中文關鍵字 類固醇  熱痛過敏現象  去磷酸酶  性別差異  辣椒素受體  急性痛覺反應  睪脂酮 
英文關鍵字 Sex differences  Testosterone  Calcineurin  Nocifensive response  Thermal hyperalgesia  Steroids  Capsaicin receptor 
學科別分類
中文摘要 我們先前的研究顯示,雄性類固醇睪脂酮對大白鼠背根神經節細胞膜上辣椒素受體所媒介的電流反應具有抑制作用,但是雌性類固醇動情激素對辣椒素受體所媒介的電流反應卻有促進作用。此結果不但可合理解釋臨床上的發現:辣椒素在女性所誘發的痛覺反應較男性為大,並且暗示在大白鼠辣椒素所誘發的痛覺反應和熱痛過敏現象可能有性別上的差異。最近我們的實驗結果證實了這個假設。我們發現,辣椒素在雌性大白鼠所誘發的痛覺反應和熱痛過敏現象,比在雄性大白鼠所誘發的為強,且此性別差異是由動情激素所媒介的,而黃體激素並無參與。但是雄性類固醇睪脂酮是否參與此性別差異的誘發,目前則不十分清楚。因此在本研究中,我們利用動物痛覺行為測試技術及藥理學的方法,探討睪脂酮在大白鼠辣椒素誘發急性痛覺反應和熱痛過敏現象之性別差異上所擔任的角色及其作用機制。我們的結果顯示,將雄鼠兩側睪丸切除六週後,與施予假手術之對照組比較,可使原本對急性痛覺較不敏感的雄鼠變得較為敏感。重要的是,皮內注射睪脂酮可抑制去睪丸雄鼠辣椒素所誘發的急性痛覺反應,且其抑制作用呈現劑量依賴效應。此外,睪脂酮並非透過活化類鴉片受體或類大麻受體來達到其抑制作用。但是,睪脂酮對辣椒素所誘發急性痛覺反應的抑制作用,卻會被去磷酸酶抑制劑FK506的預處理所阻斷,表示睪脂酮可能透過活化去磷酸酶來達到其抑制作用。同樣地,皮內注射睪脂酮也可抑制雌鼠所誘發的急性痛覺反應,且其抑制作用呈現劑量依賴效應。此外,雄鼠在經過睪丸切除手術後,與施予假手術之對照組雄鼠比較,辣椒素所誘發的熱痛過敏現象明顯變大。皮下注射補充睪脂酮可抑制去睪丸雄鼠辣椒素所誘發的熱痛過敏現象。綜合以上結果可知,辣椒素在雄鼠所誘發的急性痛覺反應和熱痛過敏現象之所以較雌鼠為小,主要是因為雄鼠所含有的睪脂酮能與辣椒素受體間接或直接地交互作用,進而抑制了辣椒素的活性所導致。
英文摘要 We have previously shown that the male sex steroid testosterone (T) inhibits, but the female sex steroid 17beta-estradiol potentiates, the capsaicin receptor-mediated current in rat dorsal root ganglion neurons. These results not only explain the clinical findings that women experience capsaicin-induced pain as more intense than men do, but also suggest that sex differences in capsaicin-induced nociception occur in rats in vivo. Indeed, this is the case. We found that capsaicin-induced nocifensive responses and thermal hyperalgesia were significantly greater in female rats than in male rats. Furthermore, 17beta-estradiol, but not progesterone, mediated these sex differences. However, it is unclear whether T is also involved in the male’s decreased sensitivity to capsaicin-induced nociception. In the present study, we used nociceptive behavior tests and pharmacological methods to determine the role of T in sex differences in capsaicin-induced nocifensive responses and thermal hyperalgesia in rats in vivo and the mechanism of T action. Results revealed that the male’s reduced sensitivity to the capsaicin-induced nocifensive response was completely reversed by testectomy (TX) 6 weeks prior to intradermal capsaicin injection. Importantly, intradermal co-injection of T with capsaicin dose-dependently inhibited the capsaicin-induced nocifensive response in TX males. In addition, testosterone acted through an opioid- and cannabinioid-independent mechanism to attenuate the capsaicin-induced nocifensive response in TX males. However, pretreatment with the calcineurin inhibitor FK506 abolished inhibition by T of the capsaicin-induced nocifensive response in TX males, suggesting that calcineurin is involved in T action. Similarly, intradermal T injection dose-dependently inhibited the capsaicin-induced nocifensive response in female rats. Furthermore, in male rats, intraplantar capsaicin injection induced greater thermal hyperalgesia after TX compared to sham surgery. Moreover, T replacement reversed potentiation of capsaicin-induced thermal hyperalgesia in TX males. Together, these results suggest that T mediates male’s reduced sensitivities to capsaicin-induced acute pain and thermal hyperalgesia, consistent with an interaction between T and capsaicin receptors in modifying pain perception.
論文目次 Table of Contents …………………………………………………………….…… I
List of Figures ………………………………………………………..…………... III
Abstract in Chinese ……………………………………….…………………………1
Abstract ………………………………………………..…………………………….3
Introduction ………………………………………………..……………………..….5
Capsaicin, TRPV1, and nociception ……………………………………………..5
Modulation by neurosteroids of TRPV1-mediated currents, nocifensive responses, and thermal hyperalgesia ………………………………………………...……...7
Rationale and specific aims of this study ………………………………..………9
Materials and Methods ………………………………………….…………………10
Animals …………………….……………………………………………..…….10
Capsaicin Test …………….……………………………………………………10
Plantar Test …………….……………………………………………….………11
Drugs and Chemicals …………….………………………………………….…12
Statistical Analysis …………….………………………………………..………13
Results ………………………………………………………………………………14
Testosterone replacement reverses potentiation of the capsaicin- induced nocifensive response in TX male rats …………….……………………………14
Testosterone acts through an opioid- and cannabinoid-independent mechanism to attenuate the capsaicin-induced nocifensive response in TX male rats ………14
Testosterone acts through calcineurin to inhibit the capsaicin-induced nocifensive responses in TX male rats …………….……………………………15
Testosterone dose-dependently inhibits the capsaicin-induced nocifensive response in female rats …………….…………………………………...………16
Testosterone replacement reverses potentiation of capsaicin-induced thermal hyperalgesia in TX male rats …………….……………………………..………17
Discussion ……………………………………………………...……………………19
References ……………………………………………………………..……………32
About the author……………………………………………………………………41
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