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Estrogen Receptor Beta Selective Agonists as Agents to Treat Chemotherapeutic-Induced Neuropathic Pain

Ma, Jian Nong; McFarland, Krista; Olsson, Roger LU and Burstein, Ethan S. (2016) In ACS Chemical Neuroscience 7(9). p.1180-1187
Abstract

Chemotherapy-induced neuropathic pain (CINP) remains a major unmet medical need. Estrogen receptor beta (ERβ)-selective agonists represent a novel strategy for treating CINP because they are neuroprotective and may also have anticancer activity. We confirmed that ERβ-selective agonists have antiallodynic effects in the spinal nerve ligation model of neuropathic pain. We then showed that structurally diverse ERβ-selective agonists also relieved allodynia in CINP caused by taxol, oxaliplatin, and vincristine. These effects were receptor subtype specific and mediated by ERβ receptors as ERα-selective and nonselective estrogen agonists were inactive, a mixture of an ERβ and ERα agonist was inactive, and ERβ-selective antagonists blocked the... (More)

Chemotherapy-induced neuropathic pain (CINP) remains a major unmet medical need. Estrogen receptor beta (ERβ)-selective agonists represent a novel strategy for treating CINP because they are neuroprotective and may also have anticancer activity. We confirmed that ERβ-selective agonists have antiallodynic effects in the spinal nerve ligation model of neuropathic pain. We then showed that structurally diverse ERβ-selective agonists also relieved allodynia in CINP caused by taxol, oxaliplatin, and vincristine. These effects were receptor subtype specific and mediated by ERβ receptors as ERα-selective and nonselective estrogen agonists were inactive, a mixture of an ERβ and ERα agonist was inactive, and ERβ-selective antagonists blocked the effects of the ERβ-selective agonists. The efficacy and potency of ERβ-agonists was greater in male rats than females. To address the possibility that AC-186 might stimulate proliferation of cancers, rendering it unsuitable for treating CINP, we evaluated proliferative effects of AC-186 on prostate cancer cells and found it inhibited growth (LNCaP cells) or had no effect (PC3 cells) on these cells. Thus, ERβ-selective agonists exhibit potential for treating CINP.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chemotherapy, estrogen receptor beta, Neuropathic pain, oxaliplatin, taxol, vincristine
in
ACS Chemical Neuroscience
volume
7
issue
9
pages
8 pages
publisher
The American Chemical Society
external identifiers
  • scopus:84988649533
  • wos:000384041000004
ISSN
1948-7193
DOI
10.1021/acschemneuro.6b00183
language
English
LU publication?
yes
id
01be39df-f5ee-4180-b7ba-b453789d9e5c
date added to LUP
2016-11-01 12:20:39
date last changed
2017-07-06 11:47:48
@article{01be39df-f5ee-4180-b7ba-b453789d9e5c,
  abstract     = {<p>Chemotherapy-induced neuropathic pain (CINP) remains a major unmet medical need. Estrogen receptor beta (ERβ)-selective agonists represent a novel strategy for treating CINP because they are neuroprotective and may also have anticancer activity. We confirmed that ERβ-selective agonists have antiallodynic effects in the spinal nerve ligation model of neuropathic pain. We then showed that structurally diverse ERβ-selective agonists also relieved allodynia in CINP caused by taxol, oxaliplatin, and vincristine. These effects were receptor subtype specific and mediated by ERβ receptors as ERα-selective and nonselective estrogen agonists were inactive, a mixture of an ERβ and ERα agonist was inactive, and ERβ-selective antagonists blocked the effects of the ERβ-selective agonists. The efficacy and potency of ERβ-agonists was greater in male rats than females. To address the possibility that AC-186 might stimulate proliferation of cancers, rendering it unsuitable for treating CINP, we evaluated proliferative effects of AC-186 on prostate cancer cells and found it inhibited growth (LNCaP cells) or had no effect (PC3 cells) on these cells. Thus, ERβ-selective agonists exhibit potential for treating CINP.</p>},
  author       = {Ma, Jian Nong and McFarland, Krista and Olsson, Roger and Burstein, Ethan S.},
  issn         = {1948-7193},
  keyword      = {chemotherapy,estrogen receptor beta,Neuropathic pain,oxaliplatin,taxol,vincristine},
  language     = {eng},
  month        = {09},
  number       = {9},
  pages        = {1180--1187},
  publisher    = {The American Chemical Society},
  series       = {ACS Chemical Neuroscience},
  title        = {Estrogen Receptor Beta Selective Agonists as Agents to Treat Chemotherapeutic-Induced Neuropathic Pain},
  url          = {http://dx.doi.org/10.1021/acschemneuro.6b00183},
  volume       = {7},
  year         = {2016},
}