Broad modulation of neuropathic pain states by a selective estrogen receptor beta agonist

Piu, Fabrice; Cheevers, Cindy; Hyldtoft, Lene; Gardell, Luis R.; Tredici, Andria L. Del; Andersen, Carsten; Fairbairn, Luke C.; Lund, Birgitte W.; Gustafsson, Magnus; Schiffer, Hans H.; Donello, John E.; Olsson, Roger; Gil, Daniel W.; Brann, Mark R.

doi:10.1016/j.ejphar.2008.05.015

Cited by 35 publications

(42 citation statements)

References 46 publications

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“…3) was discovered by Acadia Pharmaceutical as a selective ERβ agonist [87–88] and proved to be active in vivo against neurodegenerative diseases in mouse models of Alzheimer’s disease and Parkinson’s disease. In combination with a selective androgen receptor agonist ACP-105, in male gonadectomized triple transgenic Alzheimer’s disease mice (3xTg-AD mice), AC-186 decreased amyloid-β levels in the brain by increasing the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme and improved cognition after 7 months of treatment [89].…”

Section: Update On Chemical Classes Comprising Erα and Erβ Modulatorsmentioning

confidence: 99%

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

et al. 2014

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Estrogen receptors alpha (ERα) and beta (ERβ) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. Modulation of these receptors by prospective therapeutic agents is currently being considered for prevention and treatment of a wide variety of pathological conditions, such as, cancer, metabolic and cardiovascular diseases, neurodegeneration, inflammation, and osteoporosis. This review provides an overview and update of compounds that have been recently reported as modulators of ERs, with a particular focus on their potential clinical applications.

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Section: Update On Chemical Classes Comprising Erα and Erβ Modulatorsmentioning

confidence: 99%

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

et al. 2014

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“…A single oral dose of an ERß-agonist has proven effective, but does not seem to modify pain threshold in normal animals (Piu et al, 2008). The Erb-131, an ERß-agonist, which has been shown to rapidly alleviate pain in several animal models (Piu et al, 2008), has the ability to penetrate the CNS and a central component may therefore be possible. However, ERß-agonists that do not pass the blood-brain-barrier are still effective (Leventhal et al, 2006), suggesting an additional peripheral effect.…”

Section: Are the Effects Of Estrogens On Pain Transmission Of Any Sigmentioning

confidence: 99%

“…In pharmacological studies making use of the established effects of estrogens on nociception, ERß-agonists have been shown to act as antihyperalgesics in animal models of acute inflammatory pain (Leventhal et al, 2006) as well as chronic inflammatory pain states (Gardell et al, 2008;Piu et al, 2008). A single oral dose of an ERß-agonist has proven effective, but does not seem to modify pain threshold in normal animals (Piu et al, 2008).…”

Section: Are the Effects Of Estrogens On Pain Transmission Of Any Sigmentioning

confidence: 99%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

111

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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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“…The effect of estrogen in regulation of pain has been deeply explored, and studies have revealed two estrogen receptors, ERa and ER b, which are widely located in brain, spinal cord, and DRG [7]. Estrogen could act on ERs and exert an anti-hyperalgesic effect to nociception, and subsequently modulate pain [25,26]. However, the present study demonstrated that ovariectomy induced mechanical and thermal hyperalgesia could be partially alleviated by the administration of a TNF-a blocker (Figs.…”

Section: Discussionmentioning

confidence: 99%

Blocking TNF-α with infliximab alleviates ovariectomy induced mechanical and thermal hyperalgesia in rats

Chen

Xie

et al. 2011

Neurol Sci

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Studies have proved an increased expression of tumor necrosis factor alpha (TNF-α) in estrogen deficiency animals, and TNF-α also plays a role in inflammation and neuropathic pain. This study aimed to explore the relationship between TNF-α and ovariectomy induced hyperalgesia. 36 female Sparague-Dawley were included, estrogen depletion models were established by ovariectomy. Then infliximab (a TNF-α blocker) was administrated to the ovariectomized rats for 8 weeks. Pain behavioral tests were performed once a week. The bone mineral density (BMD), serum estradiol and TNF-α level were determined at the 8th week after ovariectomy. The expression of TNF-α in lumbar 5 dorsal root ganglions (L5 DRGs) was examined by immunofluorescence method. Significant hyperalgesia to mechanical and thermal stimuli in groups Ovx-1 and Ovx-2 was observed 1 week after the operation. After treated with infliximab, the pain threshold of Ovx-2 was partially restored, although still lower than the Sham group. The serum TNF-α level of Ovx-1 was significantly higher than Sham and Ovx-2. TNF-α immunofluorescence indicated a significant increase in the expression of TNF-α at L5 DRGs in group Ovx-1 when compared with groups Sham and Ovx-2. The BMD of group Ovx-2 was significantly higher than group Ovx-1 and lower than group Sham. In conclusion, TNF-α plays an important role in estrogen deficiency induced mechanical and thermal hyperalgesia, and DRG may be one site on which TNF-α acts to cause hyperalgesia. Blocking the effect of TNF-α could partially alleviate the estrogen deficiency induced hyperalgesia in rats. Thus, TNF-α may contribute to chronic pain in postmenopausal women.

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Broad modulation of neuropathic pain states by a selective estrogen receptor beta agonist

Cited by 35 publications

References 46 publications

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

Estrogenic influences in pain processing

Blocking TNF-α with infliximab alleviates ovariectomy induced mechanical and thermal hyperalgesia in rats

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