Loading…

Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain

Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/k...

Full description

Saved in:
Bibliographic Details
Published in:Molecular pain 2021, Vol.17, p.17448069211003375-17448069211003375
Main Authors: Okerman, Travis, Jurgenson, Taylor, Moore, Madelyn, Klein, Amanda H
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c466t-50fbd168844db8574b2ca5e5b3d28610e204a78229ed671959b0632c77c13e703
cites cdi_FETCH-LOGICAL-c466t-50fbd168844db8574b2ca5e5b3d28610e204a78229ed671959b0632c77c13e703
container_end_page 17448069211003375
container_issue
container_start_page 17448069211003375
container_title Molecular pain
container_volume 17
creator Okerman, Travis
Jurgenson, Taylor
Moore, Madelyn
Klein, Amanda H
description Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.
doi_str_mv 10.1177/17448069211003375
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7983416</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_17448069211003375</sage_id><sourcerecordid>2613260710</sourcerecordid><originalsourceid>FETCH-LOGICAL-c466t-50fbd168844db8574b2ca5e5b3d28610e204a78229ed671959b0632c77c13e703</originalsourceid><addsrcrecordid>eNp1ks9uFSEUxifGxv7RB3BjSNy4oYVhgJmNSdNorVbroq4nDHPuHSoDU2Bq7qv16WS8tVZNFwQ4_M53vkNOUbyk5JBSKY-orKqaiKaklBDGJH9S7C0xvASfPjjvFvsxXmVGEkGfFbuZrTiryV5xe-YG05lkvEN-hdIAaBp8zMs4H3O8B8Twd-NUBHz86RLrjbZGo9PPX7HGH2eHvuAEYcyARVsMRbPON-PWaFJp-KE2SKUEblYJ4q8KPdyA9dMILi1FRx-mwThAyVsIymlAxiGV43NWG30PdsEczMEvirn8pIx7XuyslI3w4m4_KL69f3d58gGfX5yenRyfY10JkTAnq66noq6rqu9qLquu1IoD71hf1oISKEmlZF2WDfRC0oY3HRGs1FJqykASdlC83epOczdCr7ProGw7BTOqsGm9Mu3fL84M7drftLKpWUVFFnhzJxD89QwxtaOJGqxVDnKLbckJEzKb4Rl9_Q965eeQfzNTgrJSEEkXR3RL6eBjDLC6N0NJu0xG-99k5JxXD7u4z_g9Chk43AJRreFP2ccVfwJmqsPK</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2613260710</pqid></control><display><type>article</type><title>Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain</title><source>Publicly Available Content Database</source><source>Sage Journals GOLD Open Access 2024</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Okerman, Travis ; Jurgenson, Taylor ; Moore, Madelyn ; Klein, Amanda H</creator><creatorcontrib>Okerman, Travis ; Jurgenson, Taylor ; Moore, Madelyn ; Klein, Amanda H</creatorcontrib><description>Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.</description><identifier>ISSN: 1744-8069</identifier><identifier>EISSN: 1744-8069</identifier><identifier>DOI: 10.1177/17448069211003375</identifier><identifier>PMID: 33745380</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; AKT1 protein ; Analgesics ; Analgesics - pharmacology ; Animals ; c-Jun protein ; Cyclic GMP ; Cyclic GMP - metabolism ; Disease Models, Animal ; Dorsal root ganglia ; Drug tolerance ; Drug Tolerance - physiology ; Gene expression ; Intracellular ; Intracellular signalling ; JNK Mitogen-Activated Protein Kinases - metabolism ; JNK protein ; Kinases ; Micro Report ; Morphine ; Morphine - pharmacology ; Nervous system ; Neuralgia - metabolism ; Opioids ; Peripheral neuropathy ; Phosphatidylinositol 3-Kinases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; PTEN protein ; Quercetin ; Sciatic nerve ; Signal transduction ; Spinal cord ; Spinal nerves ; Spinal Nerves - metabolism ; Thalidomide ; Transcription factors</subject><ispartof>Molecular pain, 2021, Vol.17, p.17448069211003375-17448069211003375</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021 2021 SAGE Publications Inc., unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-50fbd168844db8574b2ca5e5b3d28610e204a78229ed671959b0632c77c13e703</citedby><cites>FETCH-LOGICAL-c466t-50fbd168844db8574b2ca5e5b3d28610e204a78229ed671959b0632c77c13e703</cites><orcidid>0000-0002-3433-2180</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983416/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2613260710?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,21944,25730,27829,27899,27900,27901,36988,36989,44565,44920,45308,53765,53767</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33745380$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Okerman, Travis</creatorcontrib><creatorcontrib>Jurgenson, Taylor</creatorcontrib><creatorcontrib>Moore, Madelyn</creatorcontrib><creatorcontrib>Klein, Amanda H</creatorcontrib><title>Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain</title><title>Molecular pain</title><addtitle>Mol Pain</addtitle><description>Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>AKT1 protein</subject><subject>Analgesics</subject><subject>Analgesics - pharmacology</subject><subject>Animals</subject><subject>c-Jun protein</subject><subject>Cyclic GMP</subject><subject>Cyclic GMP - metabolism</subject><subject>Disease Models, Animal</subject><subject>Dorsal root ganglia</subject><subject>Drug tolerance</subject><subject>Drug Tolerance - physiology</subject><subject>Gene expression</subject><subject>Intracellular</subject><subject>Intracellular signalling</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>JNK protein</subject><subject>Kinases</subject><subject>Micro Report</subject><subject>Morphine</subject><subject>Morphine - pharmacology</subject><subject>Nervous system</subject><subject>Neuralgia - metabolism</subject><subject>Opioids</subject><subject>Peripheral neuropathy</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>PTEN protein</subject><subject>Quercetin</subject><subject>Sciatic nerve</subject><subject>Signal transduction</subject><subject>Spinal cord</subject><subject>Spinal nerves</subject><subject>Spinal Nerves - metabolism</subject><subject>Thalidomide</subject><subject>Transcription factors</subject><issn>1744-8069</issn><issn>1744-8069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>PIMPY</sourceid><recordid>eNp1ks9uFSEUxifGxv7RB3BjSNy4oYVhgJmNSdNorVbroq4nDHPuHSoDU2Bq7qv16WS8tVZNFwQ4_M53vkNOUbyk5JBSKY-orKqaiKaklBDGJH9S7C0xvASfPjjvFvsxXmVGEkGfFbuZrTiryV5xe-YG05lkvEN-hdIAaBp8zMs4H3O8B8Twd-NUBHz86RLrjbZGo9PPX7HGH2eHvuAEYcyARVsMRbPON-PWaFJp-KE2SKUEblYJ4q8KPdyA9dMILi1FRx-mwThAyVsIymlAxiGV43NWG30PdsEczMEvirn8pIx7XuyslI3w4m4_KL69f3d58gGfX5yenRyfY10JkTAnq66noq6rqu9qLquu1IoD71hf1oISKEmlZF2WDfRC0oY3HRGs1FJqykASdlC83epOczdCr7ProGw7BTOqsGm9Mu3fL84M7drftLKpWUVFFnhzJxD89QwxtaOJGqxVDnKLbckJEzKb4Rl9_Q965eeQfzNTgrJSEEkXR3RL6eBjDLC6N0NJu0xG-99k5JxXD7u4z_g9Chk43AJRreFP2ccVfwJmqsPK</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Okerman, Travis</creator><creator>Jurgenson, Taylor</creator><creator>Moore, Madelyn</creator><creator>Klein, Amanda H</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3433-2180</orcidid></search><sort><creationdate>2021</creationdate><title>Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain</title><author>Okerman, Travis ; Jurgenson, Taylor ; Moore, Madelyn ; Klein, Amanda H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-50fbd168844db8574b2ca5e5b3d28610e204a78229ed671959b0632c77c13e703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>AKT1 protein</topic><topic>Analgesics</topic><topic>Analgesics - pharmacology</topic><topic>Animals</topic><topic>c-Jun protein</topic><topic>Cyclic GMP</topic><topic>Cyclic GMP - metabolism</topic><topic>Disease Models, Animal</topic><topic>Dorsal root ganglia</topic><topic>Drug tolerance</topic><topic>Drug Tolerance - physiology</topic><topic>Gene expression</topic><topic>Intracellular</topic><topic>Intracellular signalling</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>JNK protein</topic><topic>Kinases</topic><topic>Micro Report</topic><topic>Morphine</topic><topic>Morphine - pharmacology</topic><topic>Nervous system</topic><topic>Neuralgia - metabolism</topic><topic>Opioids</topic><topic>Peripheral neuropathy</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>PTEN protein</topic><topic>Quercetin</topic><topic>Sciatic nerve</topic><topic>Signal transduction</topic><topic>Spinal cord</topic><topic>Spinal nerves</topic><topic>Spinal Nerves - metabolism</topic><topic>Thalidomide</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Okerman, Travis</creatorcontrib><creatorcontrib>Jurgenson, Taylor</creatorcontrib><creatorcontrib>Moore, Madelyn</creatorcontrib><creatorcontrib>Klein, Amanda H</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health &amp; Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health &amp; Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Okerman, Travis</au><au>Jurgenson, Taylor</au><au>Moore, Madelyn</au><au>Klein, Amanda H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain</atitle><jtitle>Molecular pain</jtitle><addtitle>Mol Pain</addtitle><date>2021</date><risdate>2021</risdate><volume>17</volume><spage>17448069211003375</spage><epage>17448069211003375</epage><pages>17448069211003375-17448069211003375</pages><issn>1744-8069</issn><eissn>1744-8069</eissn><abstract>Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>33745380</pmid><doi>10.1177/17448069211003375</doi><orcidid>https://orcid.org/0000-0002-3433-2180</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1744-8069
ispartof Molecular pain, 2021, Vol.17, p.17448069211003375-17448069211003375
issn 1744-8069
1744-8069
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7983416
source Publicly Available Content Database; Sage Journals GOLD Open Access 2024; PubMed Central; Free Full-Text Journals in Chemistry
subjects 1-Phosphatidylinositol 3-kinase
AKT protein
AKT1 protein
Analgesics
Analgesics - pharmacology
Animals
c-Jun protein
Cyclic GMP
Cyclic GMP - metabolism
Disease Models, Animal
Dorsal root ganglia
Drug tolerance
Drug Tolerance - physiology
Gene expression
Intracellular
Intracellular signalling
JNK Mitogen-Activated Protein Kinases - metabolism
JNK protein
Kinases
Micro Report
Morphine
Morphine - pharmacology
Nervous system
Neuralgia - metabolism
Opioids
Peripheral neuropathy
Phosphatidylinositol 3-Kinases - metabolism
Proto-Oncogene Proteins c-akt - metabolism
PTEN protein
Quercetin
Sciatic nerve
Signal transduction
Spinal cord
Spinal nerves
Spinal Nerves - metabolism
Thalidomide
Transcription factors
title Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-25T11%3A50%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20the%20phosphoinositide%203-kinase-AKT-cyclic%20GMP-c-Jun%20N-terminal%20kinase%20signaling%20pathway%20attenuates%20the%20development%20of%20morphine%20tolerance%20in%20a%20mouse%20model%20of%20neuropathic%20pain&rft.jtitle=Molecular%20pain&rft.au=Okerman,%20Travis&rft.date=2021&rft.volume=17&rft.spage=17448069211003375&rft.epage=17448069211003375&rft.pages=17448069211003375-17448069211003375&rft.issn=1744-8069&rft.eissn=1744-8069&rft_id=info:doi/10.1177/17448069211003375&rft_dat=%3Cproquest_pubme%3E2613260710%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c466t-50fbd168844db8574b2ca5e5b3d28610e204a78229ed671959b0632c77c13e703%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2613260710&rft_id=info:pmid/33745380&rft_sage_id=10.1177_17448069211003375&rfr_iscdi=true