Contrasting Alterations to Synaptic and Intrinsic Properties in Upper-Cervical Superficial Dorsal Horn Neurons following Acute Neck Muscle Inflammation
Background: Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Acc...
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description | Background:
Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons.
Results:
Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2 g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40 μl of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2 hrs. Mice in each group were sacrificed at 2 hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I – II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ∼20% in neurons from carrageenan-injected mice versus control and sham animals (20.63 ± 1.05 vs. 24.64 ± 0.91 and 25.87 ± 1.32 pA, respectively). The amplitude (238 ± 33 vs. 494 ± 96 and 593 ± 167 pA) and inactivation time constant (12.9 ± 1.5 vs. 22.1 ± 3.6 and 15.3 ± 1.4 ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice.
Conclusions:
Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation. |
doi_str_mv | 10.1186/1744-8069-10-25 |
format | Article |
fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4032164</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A539690014</galeid><sage_id>10.1186_1744-8069-10-25</sage_id><sourcerecordid>A539690014</sourcerecordid><originalsourceid>FETCH-LOGICAL-b645t-4a561e520193f09b0f29dc0c4146c1856e661a454e8dbab446bb7dc396e42d4c3</originalsourceid><addsrcrecordid>eNp9kstu1DAUhiMEoqWwZocisWFBWt-TbJCG4dJK5SKVri3HORlcHDu1k6I-Ca-L0ynDDGqRF_Y5_vyfm7PsOUaHGFfiCJeMFRUSdYFRQfiDbH_jebh13suexHiBEC2RwI-zPcJKwmuB9rNfS-_GoOJo3Cpf2BGCGo13MR99fnbt1DAanSvX5icJMy4m62vwA4TRQMyNy8-HZBRLCFdGK5ufTcnsjDbp_M6HmLZjH1z-GaYwy3beWv_zJpieRkh-_SP_NEVtIYXorOr7mwSeZo86ZSM8u90PsvMP778tj4vTLx9PlovTohGMjwVTXGDgBOGadqhuUEfqViPNMBMaV1yAEFgxzqBqG9UwJpqmbDWtBTDSMk0Psjdr3WFqemg1zN2wcgimV-FaemXk7o0z3-XKX0mGKMGCJYG3a4HG-HsEdm-07-U8GDkPRmIkCU8ir26zCP5ygjjK3kQN1ioHfooSc8oqRhGtE_ryH_TCT8GlHklSI15yXNLqfxTmpMK8opX4S62UBWlc51OGeg4tFzz1qEYIzxUe3kGl1UJvtHfQmeTfeXC0fqCDjzFAt-lGqnb-tnfU_2J7Chv-zz9NwOs1ENUKtmq5R-83hcz2jw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1528158386</pqid></control><display><type>article</type><title>Contrasting Alterations to Synaptic and Intrinsic Properties in Upper-Cervical Superficial Dorsal Horn Neurons following Acute Neck Muscle Inflammation</title><source>MEDLINE</source><source>Sage Journals GOLD Open Access 2024</source><source>Springer Nature OA Free Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Harris, Belinda M ; Hughes, David I ; Bolton, Philip S ; Tadros, Melissa A ; Callister, Robert J ; Graham, Brett A</creator><creatorcontrib>Harris, Belinda M ; Hughes, David I ; Bolton, Philip S ; Tadros, Melissa A ; Callister, Robert J ; Graham, Brett A</creatorcontrib><description>Background:
Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons.
Results:
Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2 g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40 μl of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2 hrs. Mice in each group were sacrificed at 2 hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I – II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ∼20% in neurons from carrageenan-injected mice versus control and sham animals (20.63 ± 1.05 vs. 24.64 ± 0.91 and 25.87 ± 1.32 pA, respectively). The amplitude (238 ± 33 vs. 494 ± 96 and 593 ± 167 pA) and inactivation time constant (12.9 ± 1.5 vs. 22.1 ± 3.6 and 15.3 ± 1.4 ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice.
Conclusions:
Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation.</description><identifier>ISSN: 1744-8069</identifier><identifier>EISSN: 1744-8069</identifier><identifier>DOI: 10.1186/1744-8069-10-25</identifier><identifier>PMID: 24725960</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Analysis ; Analysis of Variance ; Animal experimentation ; Animal models ; Animals ; Brain slice preparation ; c-Fos protein ; Care and treatment ; Carrageenan - toxicity ; Carrageenans ; Carrageenin ; Chronic pain ; Complications and side effects ; Diagnosis ; Disease Models, Animal ; Dorsal horn ; Electric Stimulation ; Excitatory postsynaptic potentials ; Excitatory Postsynaptic Potentials - drug effects ; Excitatory Postsynaptic Potentials - physiology ; Functional Laterality - drug effects ; Functional Laterality - physiology ; Ganglia, Spinal - pathology ; Health aspects ; In Vitro Techniques ; Inflammation ; Labeling ; Male ; Membrane potential ; Mice ; Mice, Inbred C57BL ; Myositis - chemically induced ; Myositis - complications ; Neck Muscles - pathology ; Neurons ; Neurophysiology ; Neuroprotection ; Neurosciences ; Patch-Clamp Techniques ; Patient outcomes ; Physiological aspects ; Proto-Oncogene Proteins c-fos - metabolism ; Risk factors ; Rodents ; Sensory Receptor Cells - physiology ; Spinal cord ; Studies ; Synapses - drug effects ; Synapses - physiology</subject><ispartof>Molecular pain, 2014-04, Vol.10 (1), p.25-25</ispartof><rights>2014 Harris et al</rights><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Harris et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>2014 Harris et al. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright © 2014 Harris et al.; licensee BioMed Central Ltd. 2014 Harris et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b645t-4a561e520193f09b0f29dc0c4146c1856e661a454e8dbab446bb7dc396e42d4c3</citedby><cites>FETCH-LOGICAL-b645t-4a561e520193f09b0f29dc0c4146c1856e661a454e8dbab446bb7dc396e42d4c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032164/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032164/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,21966,27853,27924,27925,44945,45333,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24725960$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harris, Belinda M</creatorcontrib><creatorcontrib>Hughes, David I</creatorcontrib><creatorcontrib>Bolton, Philip S</creatorcontrib><creatorcontrib>Tadros, Melissa A</creatorcontrib><creatorcontrib>Callister, Robert J</creatorcontrib><creatorcontrib>Graham, Brett A</creatorcontrib><title>Contrasting Alterations to Synaptic and Intrinsic Properties in Upper-Cervical Superficial Dorsal Horn Neurons following Acute Neck Muscle Inflammation</title><title>Molecular pain</title><addtitle>Mol Pain</addtitle><description>Background:
Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons.
Results:
Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2 g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40 μl of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2 hrs. Mice in each group were sacrificed at 2 hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I – II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ∼20% in neurons from carrageenan-injected mice versus control and sham animals (20.63 ± 1.05 vs. 24.64 ± 0.91 and 25.87 ± 1.32 pA, respectively). The amplitude (238 ± 33 vs. 494 ± 96 and 593 ± 167 pA) and inactivation time constant (12.9 ± 1.5 vs. 22.1 ± 3.6 and 15.3 ± 1.4 ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice.
Conclusions:
Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation.</description><subject>Analysis</subject><subject>Analysis of Variance</subject><subject>Animal experimentation</subject><subject>Animal models</subject><subject>Animals</subject><subject>Brain slice preparation</subject><subject>c-Fos protein</subject><subject>Care and treatment</subject><subject>Carrageenan - toxicity</subject><subject>Carrageenans</subject><subject>Carrageenin</subject><subject>Chronic pain</subject><subject>Complications and side effects</subject><subject>Diagnosis</subject><subject>Disease Models, Animal</subject><subject>Dorsal horn</subject><subject>Electric Stimulation</subject><subject>Excitatory postsynaptic potentials</subject><subject>Excitatory Postsynaptic Potentials - drug effects</subject><subject>Excitatory Postsynaptic Potentials - physiology</subject><subject>Functional Laterality - drug effects</subject><subject>Functional Laterality - physiology</subject><subject>Ganglia, Spinal - pathology</subject><subject>Health aspects</subject><subject>In Vitro Techniques</subject><subject>Inflammation</subject><subject>Labeling</subject><subject>Male</subject><subject>Membrane potential</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Myositis - chemically induced</subject><subject>Myositis - complications</subject><subject>Neck Muscles - pathology</subject><subject>Neurons</subject><subject>Neurophysiology</subject><subject>Neuroprotection</subject><subject>Neurosciences</subject><subject>Patch-Clamp Techniques</subject><subject>Patient outcomes</subject><subject>Physiological aspects</subject><subject>Proto-Oncogene Proteins c-fos - metabolism</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Sensory Receptor Cells - physiology</subject><subject>Spinal cord</subject><subject>Studies</subject><subject>Synapses - drug effects</subject><subject>Synapses - physiology</subject><issn>1744-8069</issn><issn>1744-8069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp9kstu1DAUhiMEoqWwZocisWFBWt-TbJCG4dJK5SKVri3HORlcHDu1k6I-Ca-L0ynDDGqRF_Y5_vyfm7PsOUaHGFfiCJeMFRUSdYFRQfiDbH_jebh13suexHiBEC2RwI-zPcJKwmuB9rNfS-_GoOJo3Cpf2BGCGo13MR99fnbt1DAanSvX5icJMy4m62vwA4TRQMyNy8-HZBRLCFdGK5ufTcnsjDbp_M6HmLZjH1z-GaYwy3beWv_zJpieRkh-_SP_NEVtIYXorOr7mwSeZo86ZSM8u90PsvMP778tj4vTLx9PlovTohGMjwVTXGDgBOGadqhuUEfqViPNMBMaV1yAEFgxzqBqG9UwJpqmbDWtBTDSMk0Psjdr3WFqemg1zN2wcgimV-FaemXk7o0z3-XKX0mGKMGCJYG3a4HG-HsEdm-07-U8GDkPRmIkCU8ir26zCP5ygjjK3kQN1ioHfooSc8oqRhGtE_ryH_TCT8GlHklSI15yXNLqfxTmpMK8opX4S62UBWlc51OGeg4tFzz1qEYIzxUe3kGl1UJvtHfQmeTfeXC0fqCDjzFAt-lGqnb-tnfU_2J7Chv-zz9NwOs1ENUKtmq5R-83hcz2jw</recordid><startdate>20140412</startdate><enddate>20140412</enddate><creator>Harris, Belinda M</creator><creator>Hughes, David I</creator><creator>Bolton, Philip S</creator><creator>Tadros, Melissa A</creator><creator>Callister, Robert J</creator><creator>Graham, Brett A</creator><general>SAGE Publications</general><general>BioMed Central Ltd</general><general>Sage Publications Ltd</general><general>BioMed Central</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>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20140412</creationdate><title>Contrasting Alterations to Synaptic and Intrinsic Properties in Upper-Cervical Superficial Dorsal Horn Neurons following Acute Neck Muscle Inflammation</title><author>Harris, Belinda M ; Hughes, David I ; Bolton, Philip S ; Tadros, Melissa A ; Callister, Robert J ; Graham, Brett A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b645t-4a561e520193f09b0f29dc0c4146c1856e661a454e8dbab446bb7dc396e42d4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis</topic><topic>Analysis of Variance</topic><topic>Animal experimentation</topic><topic>Animal models</topic><topic>Animals</topic><topic>Brain slice preparation</topic><topic>c-Fos protein</topic><topic>Care and treatment</topic><topic>Carrageenan - toxicity</topic><topic>Carrageenans</topic><topic>Carrageenin</topic><topic>Chronic pain</topic><topic>Complications and side effects</topic><topic>Diagnosis</topic><topic>Disease Models, Animal</topic><topic>Dorsal horn</topic><topic>Electric Stimulation</topic><topic>Excitatory postsynaptic potentials</topic><topic>Excitatory Postsynaptic Potentials - drug effects</topic><topic>Excitatory Postsynaptic Potentials - physiology</topic><topic>Functional Laterality - drug effects</topic><topic>Functional Laterality - physiology</topic><topic>Ganglia, Spinal - pathology</topic><topic>Health aspects</topic><topic>In Vitro Techniques</topic><topic>Inflammation</topic><topic>Labeling</topic><topic>Male</topic><topic>Membrane potential</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Myositis - chemically induced</topic><topic>Myositis - complications</topic><topic>Neck Muscles - pathology</topic><topic>Neurons</topic><topic>Neurophysiology</topic><topic>Neuroprotection</topic><topic>Neurosciences</topic><topic>Patch-Clamp Techniques</topic><topic>Patient outcomes</topic><topic>Physiological aspects</topic><topic>Proto-Oncogene Proteins c-fos - metabolism</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Sensory Receptor Cells - physiology</topic><topic>Spinal cord</topic><topic>Studies</topic><topic>Synapses - drug effects</topic><topic>Synapses - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harris, Belinda M</creatorcontrib><creatorcontrib>Hughes, David I</creatorcontrib><creatorcontrib>Bolton, Philip S</creatorcontrib><creatorcontrib>Tadros, Melissa A</creatorcontrib><creatorcontrib>Callister, Robert J</creatorcontrib><creatorcontrib>Graham, Brett A</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 & 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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</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>PubMed Central (Full Participant titles)</collection><jtitle>Molecular pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harris, Belinda M</au><au>Hughes, David I</au><au>Bolton, Philip S</au><au>Tadros, Melissa A</au><au>Callister, Robert J</au><au>Graham, Brett A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contrasting Alterations to Synaptic and Intrinsic Properties in Upper-Cervical Superficial Dorsal Horn Neurons following Acute Neck Muscle Inflammation</atitle><jtitle>Molecular pain</jtitle><addtitle>Mol Pain</addtitle><date>2014-04-12</date><risdate>2014</risdate><volume>10</volume><issue>1</issue><spage>25</spage><epage>25</epage><pages>25-25</pages><issn>1744-8069</issn><eissn>1744-8069</eissn><abstract>Background:
Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons.
Results:
Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2 g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40 μl of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2 hrs. Mice in each group were sacrificed at 2 hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I – II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ∼20% in neurons from carrageenan-injected mice versus control and sham animals (20.63 ± 1.05 vs. 24.64 ± 0.91 and 25.87 ± 1.32 pA, respectively). The amplitude (238 ± 33 vs. 494 ± 96 and 593 ± 167 pA) and inactivation time constant (12.9 ± 1.5 vs. 22.1 ± 3.6 and 15.3 ± 1.4 ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice.
Conclusions:
Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>24725960</pmid><doi>10.1186/1744-8069-10-25</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Analysis Analysis of Variance Animal experimentation Animal models Animals Brain slice preparation c-Fos protein Care and treatment Carrageenan - toxicity Carrageenans Carrageenin Chronic pain Complications and side effects Diagnosis Disease Models, Animal Dorsal horn Electric Stimulation Excitatory postsynaptic potentials Excitatory Postsynaptic Potentials - drug effects Excitatory Postsynaptic Potentials - physiology Functional Laterality - drug effects Functional Laterality - physiology Ganglia, Spinal - pathology Health aspects In Vitro Techniques Inflammation Labeling Male Membrane potential Mice Mice, Inbred C57BL Myositis - chemically induced Myositis - complications Neck Muscles - pathology Neurons Neurophysiology Neuroprotection Neurosciences Patch-Clamp Techniques Patient outcomes Physiological aspects Proto-Oncogene Proteins c-fos - metabolism Risk factors Rodents Sensory Receptor Cells - physiology Spinal cord Studies Synapses - drug effects Synapses - physiology |
title | Contrasting Alterations to Synaptic and Intrinsic Properties in Upper-Cervical Superficial Dorsal Horn Neurons following Acute Neck Muscle Inflammation |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T12%3A34%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Contrasting%20Alterations%20to%20Synaptic%20and%20Intrinsic%20Properties%20in%20Upper-Cervical%20Superficial%20Dorsal%20Horn%20Neurons%20following%20Acute%20Neck%20Muscle%20Inflammation&rft.jtitle=Molecular%20pain&rft.au=Harris,%20Belinda%20M&rft.date=2014-04-12&rft.volume=10&rft.issue=1&rft.spage=25&rft.epage=25&rft.pages=25-25&rft.issn=1744-8069&rft.eissn=1744-8069&rft_id=info:doi/10.1186/1744-8069-10-25&rft_dat=%3Cgale_pubme%3EA539690014%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1528158386&rft_id=info:pmid/24725960&rft_galeid=A539690014&rft_sage_id=10.1186_1744-8069-10-25&rfr_iscdi=true |