Mechanisms Underlying the Effects of Pregnenolone Sulfate and 17β-Estradiol on Capsaicin-Induced Thermal Hyperalgesia and Nocifensive Responses in Male Rats
碩士 === 國立成功大學 === 生理學研究所 === 95 === The capsaicin receptor is expressed predominantly by sensory neurons and has been implicated in nociception and inflammatory thermal hyperalgesia. Previous studies from our laboratory have shown that the neurosteroid pregnenolone sulfate (PS) inhibits, but the fem...
Main Authors: | , |
---|---|
Other Authors: | |
Format: | Others |
Language: | en_US |
Published: |
2007
|
Online Access: | http://ndltd.ncl.edu.tw/handle/69807462657241770779 |
id |
ndltd-TW-095NCKU5116005 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-TW-095NCKU51160052015-10-13T14:16:11Z http://ndltd.ncl.edu.tw/handle/69807462657241770779 Mechanisms Underlying the Effects of Pregnenolone Sulfate and 17β-Estradiol on Capsaicin-Induced Thermal Hyperalgesia and Nocifensive Responses in Male Rats 硫酸孕烯醇酮及雌二醇對辣椒素誘發雄性大白鼠產生熱痛過敏現象及急性痛之調節作用的機制 Chao-wei Chen 陳兆偉 碩士 國立成功大學 生理學研究所 95 The capsaicin receptor is expressed predominantly by sensory neurons and has been implicated in nociception and inflammatory thermal hyperalgesia. Previous studies from our laboratory have shown that the neurosteroid pregnenolone sulfate (PS) inhibits, but the female sex steroid 17β-estradiol (E2) potentiates, both the capsaicin receptor-mediated current in male rat dorsal root ganglion neurons and the capsaicin receptor-mediated nocifensive response in male rats. However, it is unclear whether PS and E2 also have modulatory effects on capsaicin-induced thermal hyperalegsia. In the present study, we used pharmacological methods and nociceptive behavioral tests to characterize the effects of PS and E2 on capsaicin-induced heat hypersensitivity and nocifensive responses in male rats in vivo. Our results revealed that intraplantar injection of PS dose-dependently attenuated capsaicin-induced thermal hyperalgesia. PS alone had no effect on heat sensitivity, indicating that the effect of PS on capsaicin-induced thermal hyperalgesia was not due to an increase in nociceptive threshold. Moreover, inhibition by PS of capsaicin-induced thermal hyperalgesia was not reduced by FK506, a selective calcineurin inhibitor, suggesting that the effect of PS was not mediated by calcineurin. Furthermore, intraplantar injection of E2 potentiated capsaicin-induced thermal hyperalgesia in male rats. In addition, co-injection of E2 but not 17α-estradiol with a subthreshold dose of capsaicin induced thermal hyperalgesia, indicating that the reduction by E2 of the capsaicin threshold for thermal hyperalgesia was stereospecific. E2 alone did not alter the heat sensitivity. Administration of capsazepine, a capsaicin receptor antagonist, blocked thermal hyperalgesia induced by co-injection of subthreshold doses of E2 and capsaicin, suggesting that thermal hyperalgesia was mediated by the capsaicin receptor. Furthermore, pretreatment of a protein kinase C (PKC) or a PKA inhibitor completely inhibited the synergistic effect of co-injected capsaicin and E2 on thermal hyperalgesia, arguing strongly for the involvement of PKC and PKA. In contrast, administration of PKC or PKA inhibitor did not block the potentiating effect of E2 on capsaicin-induced nocifensive responses. In conclusion, these data demonstrate that PS inhibits capsaicin-induced heat hypersensitivity via a calcineurin-independent mechanism, and that PKC and PKA are involved in the reduction by E2 of the capsaicin threshold for thermal hyperalgesia but not in the potentiating effect of E2 on capsaicin-induced nocifensive responses. Fong-sen Wu 吳豐森 2007 學位論文 ; thesis 61 en_US |
collection |
NDLTD |
language |
en_US |
format |
Others
|
sources |
NDLTD |
description |
碩士 === 國立成功大學 === 生理學研究所 === 95 === The capsaicin receptor is expressed predominantly by sensory neurons and has been implicated in nociception and inflammatory thermal hyperalgesia. Previous studies from our laboratory have shown that the neurosteroid pregnenolone sulfate (PS) inhibits, but the female sex steroid 17β-estradiol (E2) potentiates, both the capsaicin receptor-mediated current in male rat dorsal root ganglion neurons and the capsaicin receptor-mediated nocifensive response in male rats. However, it is unclear whether PS and E2 also have modulatory effects on capsaicin-induced thermal hyperalegsia. In the present study, we used pharmacological methods and nociceptive behavioral tests to characterize the effects of PS and E2 on capsaicin-induced heat hypersensitivity and nocifensive responses in male rats in vivo. Our results revealed that intraplantar injection of PS dose-dependently attenuated capsaicin-induced thermal hyperalgesia. PS alone had no effect on heat sensitivity, indicating that the effect of PS on capsaicin-induced thermal hyperalgesia was not due to an increase in nociceptive threshold. Moreover, inhibition by PS of capsaicin-induced thermal hyperalgesia was not reduced by FK506, a selective calcineurin inhibitor, suggesting that the effect of PS was not mediated by calcineurin. Furthermore, intraplantar injection of E2 potentiated capsaicin-induced thermal hyperalgesia in male rats. In addition, co-injection of E2 but not 17α-estradiol with a subthreshold dose of capsaicin induced thermal hyperalgesia, indicating that the reduction by E2 of the capsaicin threshold for thermal hyperalgesia was stereospecific. E2 alone did not alter the heat sensitivity. Administration of capsazepine, a capsaicin receptor antagonist, blocked thermal hyperalgesia induced by co-injection of subthreshold doses of E2 and capsaicin, suggesting that thermal hyperalgesia was mediated by the capsaicin receptor. Furthermore, pretreatment of a protein kinase C (PKC) or a PKA inhibitor completely inhibited the synergistic effect of co-injected capsaicin and E2 on thermal hyperalgesia, arguing strongly for the involvement of PKC and PKA. In contrast, administration of PKC or PKA inhibitor did not block the potentiating effect of E2 on capsaicin-induced nocifensive responses. In conclusion, these data demonstrate that PS inhibits capsaicin-induced heat hypersensitivity via a calcineurin-independent mechanism, and that PKC and PKA are involved in the reduction by E2 of the capsaicin threshold for thermal hyperalgesia but not in the potentiating effect of E2 on capsaicin-induced nocifensive responses.
|
author2 |
Fong-sen Wu |
author_facet |
Fong-sen Wu Chao-wei Chen 陳兆偉 |
author |
Chao-wei Chen 陳兆偉 |
spellingShingle |
Chao-wei Chen 陳兆偉 Mechanisms Underlying the Effects of Pregnenolone Sulfate and 17β-Estradiol on Capsaicin-Induced Thermal Hyperalgesia and Nocifensive Responses in Male Rats |
author_sort |
Chao-wei Chen |
title |
Mechanisms Underlying the Effects of Pregnenolone Sulfate and 17β-Estradiol on Capsaicin-Induced Thermal Hyperalgesia and Nocifensive Responses in Male Rats |
title_short |
Mechanisms Underlying the Effects of Pregnenolone Sulfate and 17β-Estradiol on Capsaicin-Induced Thermal Hyperalgesia and Nocifensive Responses in Male Rats |
title_full |
Mechanisms Underlying the Effects of Pregnenolone Sulfate and 17β-Estradiol on Capsaicin-Induced Thermal Hyperalgesia and Nocifensive Responses in Male Rats |
title_fullStr |
Mechanisms Underlying the Effects of Pregnenolone Sulfate and 17β-Estradiol on Capsaicin-Induced Thermal Hyperalgesia and Nocifensive Responses in Male Rats |
title_full_unstemmed |
Mechanisms Underlying the Effects of Pregnenolone Sulfate and 17β-Estradiol on Capsaicin-Induced Thermal Hyperalgesia and Nocifensive Responses in Male Rats |
title_sort |
mechanisms underlying the effects of pregnenolone sulfate and 17β-estradiol on capsaicin-induced thermal hyperalgesia and nocifensive responses in male rats |
publishDate |
2007 |
url |
http://ndltd.ncl.edu.tw/handle/69807462657241770779 |
work_keys_str_mv |
AT chaoweichen mechanismsunderlyingtheeffectsofpregnenolonesulfateand17bestradioloncapsaicininducedthermalhyperalgesiaandnocifensiveresponsesinmalerats AT chénzhàowěi mechanismsunderlyingtheeffectsofpregnenolonesulfateand17bestradioloncapsaicininducedthermalhyperalgesiaandnocifensiveresponsesinmalerats AT chaoweichen liúsuānyùnxīchúntóngjícíèrchúnduìlàjiāosùyòufāxióngxìngdàbáishǔchǎnshēngrètòngguòmǐnxiànxiàngjíjíxìngtòngzhīdiàojiézuòyòngdejīzhì AT chénzhàowěi liúsuānyùnxīchúntóngjícíèrchúnduìlàjiāosùyòufāxióngxìngdàbáishǔchǎnshēngrètòngguòmǐnxiànxiàngjíjíxìngtòngzhīdiàojiézuòyòngdejīzhì |
_version_ |
1717750984898248704 |