Activation of Membrane Estrogen Receptors Attenuates NOP-Mediated Tactile Antihypersensitivity in a Rodent Model of Neuropathic Pain
Identifieur interne : 000713 ( Main/Exploration ); précédent : 000712; suivant : 000714Activation of Membrane Estrogen Receptors Attenuates NOP-Mediated Tactile Antihypersensitivity in a Rodent Model of Neuropathic Pain
Auteurs : Danyeal M. Wright ; Keri M. Small ; Subodh Nag ; Sukhbir S. MokhaSource :
- Brain Sciences [ 2076-3425 ] ; 2019.
Abstract
Women manifest a higher prevalence of several chronic pain disorders compared to men. We demonstrated earlier that estrogen rapidly attenuates nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP)-mediated thermal antinociception through the activation of membrane estrogen receptors (mERs). However, the effect of mER activation on NOP-mediated attenuation of tactile hypersensitivity in a neuropathic model of pain and the underlying mechanisms remain unknown. Following spared nerve injury (SNI), male and ovariectomized (OVX) female rats were intrathecally (i.t.) injected with a selective mER agonist and nociceptin/orphanin FQ (N/OFQ), the endogenous ligand for NOP, and their effects on paw withdrawal thresholds (PWTs) were tested. In addition, spinal cord tissue was used to measure changes in phosphorylated extracellular signal regulated kinase (ERK), protein kinase A (PKA), protein kinase C (PKC), and protein kinase B (Akt) levels. SNI significantly reduced PWTs in males and OVX females, indicating tactile hypersensitivity. N/OFQ restored PWTs, indicating an antihypersensitive effect. Selective mER activation attenuated the effect of N/OFQ in an antagonist-reversible manner. SNI led to a robust increase in the phosphorylation of ERK, PKA, PKC, and Akt. However, mER activation did not further affect it. Thus, we conclude that activation of mERs rapidly abolishes NOP-mediated tactile antihypersensitivity following SNI via an ERK-, PKA-, PKC-, and Akt-independent mechanism.
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DOI: 10.3390/brainsci9060147
PubMed: 31234278
PubMed Central: 6628583
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Activation of Membrane Estrogen Receptors Attenuates NOP-Mediated Tactile Antihypersensitivity in a Rodent Model of Neuropathic Pain</title><author><name sortKey="Wright, Danyeal M" sort="Wright, Danyeal M" uniqKey="Wright D" first="Danyeal M." last="Wright">Danyeal M. Wright</name></author><author><name sortKey="Small, Keri M" sort="Small, Keri M" uniqKey="Small K" first="Keri M." last="Small">Keri M. Small</name></author><author><name sortKey="Nag, Subodh" sort="Nag, Subodh" uniqKey="Nag S" first="Subodh" last="Nag">Subodh Nag</name></author><author><name sortKey="Mokha, Sukhbir S" sort="Mokha, Sukhbir S" uniqKey="Mokha S" first="Sukhbir S." last="Mokha">Sukhbir S. Mokha</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31234278</idno><idno type="pmc">6628583</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628583</idno><idno type="RBID">PMC:6628583</idno><idno type="doi">10.3390/brainsci9060147</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000B45</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B45</idno><idno type="wicri:Area/Pmc/Curation">000B45</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B45</idno><idno type="wicri:Area/Pmc/Checkpoint">000409</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000409</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:31234278</idno><idno type="wicri:Area/PubMed/Corpus">000500</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000500</idno><idno type="wicri:Area/PubMed/Curation">000500</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000500</idno><idno type="wicri:Area/PubMed/Checkpoint">000684</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000684</idno><idno type="wicri:Area/Ncbi/Merge">002257</idno><idno type="wicri:Area/Ncbi/Curation">002257</idno><idno type="wicri:Area/Ncbi/Checkpoint">002257</idno><idno type="wicri:Area/Main/Merge">000716</idno><idno type="wicri:Area/Main/Curation">000713</idno><idno type="wicri:Area/Main/Exploration">000713</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Activation of Membrane Estrogen Receptors Attenuates NOP-Mediated Tactile Antihypersensitivity in a Rodent Model of Neuropathic Pain</title><author><name sortKey="Wright, Danyeal M" sort="Wright, Danyeal M" uniqKey="Wright D" first="Danyeal M." last="Wright">Danyeal M. Wright</name></author><author><name sortKey="Small, Keri M" sort="Small, Keri M" uniqKey="Small K" first="Keri M." last="Small">Keri M. Small</name></author><author><name sortKey="Nag, Subodh" sort="Nag, Subodh" uniqKey="Nag S" first="Subodh" last="Nag">Subodh Nag</name></author><author><name sortKey="Mokha, Sukhbir S" sort="Mokha, Sukhbir S" uniqKey="Mokha S" first="Sukhbir S." last="Mokha">Sukhbir S. Mokha</name></author></analytic><series><title level="j">Brain Sciences</title><idno type="eISSN">2076-3425</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Women manifest a higher prevalence of several chronic pain disorders compared to men. We demonstrated earlier that estrogen rapidly attenuates nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP)-mediated thermal antinociception through the activation of membrane estrogen receptors (mERs). However, the effect of mER activation on NOP-mediated attenuation of tactile hypersensitivity in a neuropathic model of pain and the underlying mechanisms remain unknown. Following spared nerve injury (SNI), male and ovariectomized (OVX) female rats were intrathecally (i.t.) injected with a selective mER agonist and nociceptin/orphanin FQ (N/OFQ), the endogenous ligand for NOP, and their effects on paw withdrawal thresholds (PWTs) were tested. In addition, spinal cord tissue was used to measure changes in phosphorylated extracellular signal regulated kinase (ERK), protein kinase A (PKA), protein kinase C (PKC), and protein kinase B (Akt) levels. SNI significantly reduced PWTs in males and OVX females, indicating tactile hypersensitivity. N/OFQ restored PWTs, indicating an antihypersensitive effect. Selective mER activation attenuated the effect of N/OFQ in an antagonist-reversible manner. SNI led to a robust increase in the phosphorylation of ERK, PKA, PKC, and Akt. However, mER activation did not further affect it. Thus, we conclude that activation of mERs rapidly abolishes NOP-mediated tactile antihypersensitivity following SNI via an ERK-, PKA-, PKC-, and Akt-independent mechanism.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Edlund, M J" uniqKey="Edlund M">M.J. Edlund</name></author><author><name sortKey="Martin, B C" uniqKey="Martin B">B.C. Martin</name></author><author><name sortKey="Fan, M Y" uniqKey="Fan M">M.-Y. Fan</name></author><author><name sortKey="Devries, A" uniqKey="Devries A">A. Devries</name></author><author><name sortKey="Braden, J B" uniqKey="Braden J">J.B. 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Clark</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Mokha, Sukhbir S" sort="Mokha, Sukhbir S" uniqKey="Mokha S" first="Sukhbir S." last="Mokha">Sukhbir S. Mokha</name><name sortKey="Nag, Subodh" sort="Nag, Subodh" uniqKey="Nag S" first="Subodh" last="Nag">Subodh Nag</name><name sortKey="Small, Keri M" sort="Small, Keri M" uniqKey="Small K" first="Keri M." last="Small">Keri M. Small</name><name sortKey="Wright, Danyeal M" sort="Wright, Danyeal M" uniqKey="Wright D" first="Danyeal M." last="Wright">Danyeal M. Wright</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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