The antinociceptive effects of estradiol on adjuvant-induced hyperalgesia in rats involve activation of adrenergic and serotonergic systems

Okuda, K; Iwasaka, Hideo; Hagiwara, Satoshi; Takeshima, Naozumi; Takatani, Junji; Uchino, Tetsuya; Noguchi, Takayuki

doi:10.1007/s00540-011-1142-3

Cited by 10 publications

(8 citation statements)

References 16 publications

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“…The antinociceptive effect of one week of daily subcutaneous injections of estradiol (0.1 mg/kg or 1mg/kg) on Freund's complete adjuvant-induced hyperalgesia in rats also involves adrenergic mechanisms (Okuda et al, 2011). Other potential non-opioid candidates for executing estrogenic pain modulation at the spinal level include serotonin, GABA, calcitonin gene-related peptide (CGRP), cholecystokinin, and substance P (Duval et al, 1996;Ito et al, 2000;McCarthy et al, 1990;Micevych et al, 2002;Yang et al, 1998).…”

Section: Estrogen Receptor Neurons and The Endogenous Opioid Systemmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

109

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Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.

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Section: Estrogen Receptor Neurons and The Endogenous Opioid Systemmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

109

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“…Estradiol administration lowers thermal, mechanical and adjuvant-induced hyperalgesia in rats [24,25]. Furthermore, estradiol reduces carrageenan-induced pleurisy and acute inflammation [26,27].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, estradiol reduces carrageenan-induced pleurisy and acute inflammation [26,27]. Parts of the anti-inflammatory effects of estrogen have been linked to its interactions with adrenergic and serotonergic systems [25]. However, the full mechanisms underlying estrogen’s anti-hyperalgesic effects are still under investigation.…”

Section: Introductionmentioning

confidence: 99%

Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic–pituitary–adrenal axis activity

et al. 2015

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Although estrogen reduces inflammatory-mediated pain responses, the mechanisms behind its effects are unclear. This study investigated if estrogen modulates inflammatory signaling by reducing baseline or inflammation-induced cytokine levels in the injury-site, serum, dorsal root ganglia (DRG) and/or spinal cord. We further tested whether estrogen effects on cytokine levels are in part mediated through hypothalamic– pituitary–adrenal (HPA) axis activation. Lumbar DRG, spinal cord, serum, and hind paw tissue were analyzed for cytokine levels in 17β-estradiol-(20%) or vehicle-(100% cholesterol) treated female rats following ovariectomy/sham adrenalectomy (OVX), adrenalectomy/sham ovariectomy (ADX) or ADX + OVX operation at baseline and post formalin injection. Formalin significantly increased proinflammatory interleukin (IL)-6 levels in the paw, as well as pro- and anti-inflammatory cytokine levels in the DRG, spinal cord and serum in comparison to naïve conditions. Estrogen replacement significantly increased anti-inflammatory IL-10 levels in the DRG. Centrally, estradiol significantly decreased proinflammatory tumor necrosis factor (TNF)-α and IL-1β levels, as well as IL-10 levels, in the spinal cord in comparison to cholesterol treatment. At both sites, most estradiol modulatory effects occurred irrespective of pain or surgical condition. Estradiol alone had no influence on cytokine release in the paw or serum, indicating that estrogen effects were site-specific. Although cytokine levels were altered between surgical conditions at baseline and following formalin administration, ADX operation did not significantly reverse estradiol’s modulation of cytokine levels. These results suggest that estrogen directly regulates cytokines independent of HPA axis activity in vivo, in part by reducing cytokine levels in the spinal cord.

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“…17β-эстрадиол усиливает связывание мусцимола с ГАМК-А-рецепторами в спинном мозге у самок крыс и уменьшает содержание субстанции P [104]. Эстрадиол может оказывать антиноцицептивное действие посред-ством взаимодействия с α-2-рецепторами и серотони-новыми рецепторами в модели воспалительной гипе-ралгезии у крыс [105]. Также показано, что овариэкто-мия может индуцировать гипералгезию, и лечение эстрогеном может оказать положительное влияние на организм женщины при отсутствии яичников [106][107][108].…”

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Some of the Pain Features at the Bottom of the Back

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2017

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The antinociceptive effects of estradiol on adjuvant-induced hyperalgesia in rats involve activation of adrenergic and serotonergic systems

Abstract: Estradiol is known to perform a variety of physiological functions. Our findings suggest that one such function is antinociception via an interaction with α-2 receptors and serotonin receptors.

Cited by 10 publications

References 16 publications

Estrogenic influences in pain processing

Estrogenic influences in pain processing

Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic–pituitary–adrenal axis activity

Some of the Pain Features at the Bottom of the Back

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