Pulsed radiofrequency inhibited activation of spinal mitogen-activated protein kinases and ameliorated early neuropathic pain in rats

Background Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elu...

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Veröffentlicht in:European journal of pain 2014-05, Vol.18 (5), p.659-670
Hauptverfasser: Lin, M.-L., Lin, W.-T., Huang, R.-Y., Chen, T.-C., Huang, S.-H., Chang, C.-H., Tsai, S.-Y., Chiu, H.-W., Yeh, G.-C., Lin, C.-W., Wen, Y.-R.
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container_end_page 670
container_issue 5
container_start_page 659
container_title European journal of pain
container_volume 18
creator Lin, M.-L.
Lin, W.-T.
Huang, R.-Y.
Chen, T.-C.
Huang, S.-H.
Chang, C.-H.
Tsai, S.-Y.
Chiu, H.-W.
Yeh, G.-C.
Lin, C.-W.
Wen, Y.-R.
description Background Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs). Methods In a rat spinal nerve ligation (SNL) model, a low‐volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p‐ERK and p‐p38, as well as TNF‐α level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immunofluorescence staining. Results We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p‐ERK and p‐p38 in the spinal dorsal horn. PRF significantly attenuated SNL‐induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF‐α in the spinal dorsal horn throughout the course. Conclusions Low‐volt PRF significantly ameliorated SNL‐induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down‐regulating spinal MAPK activations and activation‐mediated cytokine release. We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.
doi_str_mv 10.1002/j.1532-2149.2013.00419.x
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Even fewer knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs). Methods In a rat spinal nerve ligation (SNL) model, a low‐volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p‐ERK and p‐p38, as well as TNF‐α level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immunofluorescence staining. Results We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p‐ERK and p‐p38 in the spinal dorsal horn. PRF significantly attenuated SNL‐induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF‐α in the spinal dorsal horn throughout the course. Conclusions Low‐volt PRF significantly ameliorated SNL‐induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down‐regulating spinal MAPK activations and activation‐mediated cytokine release. We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.</description><identifier>ISSN: 1090-3801</identifier><identifier>EISSN: 1532-2149</identifier><identifier>DOI: 10.1002/j.1532-2149.2013.00419.x</identifier><identifier>PMID: 25493301</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Acute Disease ; Animals ; Behavior, Animal ; Disease Models, Animal ; Down-Regulation - radiation effects ; Enzyme Activation - radiation effects ; Ganglia, Spinal - radiation effects ; Hyperalgesia - prevention &amp; control ; Immunohistochemistry ; Ligation ; Male ; Mitogen-Activated Protein Kinases - metabolism ; Neuralgia - enzymology ; Neuralgia - therapy ; Neuroglia - radiation effects ; Nociception - radiation effects ; p38 Mitogen-Activated Protein Kinases - metabolism ; Pain Measurement ; Pulsed Radiofrequency Treatment ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves - enzymology ; Spinal Nerves - injuries ; Spinal Nerves - radiation effects ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>European journal of pain, 2014-05, Vol.18 (5), p.659-670</ispartof><rights>2013 European Pain Federation ‐ EFIC</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4729-7c08b66e23b7e60e90f7582c7c0a1cdb421a83aa2b84d4044c1d494fdad57c013</citedby><cites>FETCH-LOGICAL-c4729-7c08b66e23b7e60e90f7582c7c0a1cdb421a83aa2b84d4044c1d494fdad57c013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fj.1532-2149.2013.00419.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fj.1532-2149.2013.00419.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25493301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, M.-L.</creatorcontrib><creatorcontrib>Lin, W.-T.</creatorcontrib><creatorcontrib>Huang, R.-Y.</creatorcontrib><creatorcontrib>Chen, T.-C.</creatorcontrib><creatorcontrib>Huang, S.-H.</creatorcontrib><creatorcontrib>Chang, C.-H.</creatorcontrib><creatorcontrib>Tsai, S.-Y.</creatorcontrib><creatorcontrib>Chiu, H.-W.</creatorcontrib><creatorcontrib>Yeh, G.-C.</creatorcontrib><creatorcontrib>Lin, C.-W.</creatorcontrib><creatorcontrib>Wen, Y.-R.</creatorcontrib><title>Pulsed radiofrequency inhibited activation of spinal mitogen-activated protein kinases and ameliorated early neuropathic pain in rats</title><title>European journal of pain</title><addtitle>EJP</addtitle><description>Background Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs). Methods In a rat spinal nerve ligation (SNL) model, a low‐volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p‐ERK and p‐p38, as well as TNF‐α level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immunofluorescence staining. Results We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p‐ERK and p‐p38 in the spinal dorsal horn. PRF significantly attenuated SNL‐induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF‐α in the spinal dorsal horn throughout the course. Conclusions Low‐volt PRF significantly ameliorated SNL‐induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down‐regulating spinal MAPK activations and activation‐mediated cytokine release. 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Lin, W.-T. ; Huang, R.-Y. ; Chen, T.-C. ; Huang, S.-H. ; Chang, C.-H. ; Tsai, S.-Y. ; Chiu, H.-W. ; Yeh, G.-C. ; Lin, C.-W. ; Wen, Y.-R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4729-7c08b66e23b7e60e90f7582c7c0a1cdb421a83aa2b84d4044c1d494fdad57c013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acute Disease</topic><topic>Animals</topic><topic>Behavior, Animal</topic><topic>Disease Models, Animal</topic><topic>Down-Regulation - radiation effects</topic><topic>Enzyme Activation - radiation effects</topic><topic>Ganglia, Spinal - radiation effects</topic><topic>Hyperalgesia - prevention &amp; control</topic><topic>Immunohistochemistry</topic><topic>Ligation</topic><topic>Male</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Neuralgia - enzymology</topic><topic>Neuralgia - therapy</topic><topic>Neuroglia - radiation effects</topic><topic>Nociception - radiation effects</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Pain Measurement</topic><topic>Pulsed Radiofrequency Treatment</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spinal Nerves - enzymology</topic><topic>Spinal Nerves - injuries</topic><topic>Spinal Nerves - radiation effects</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, M.-L.</creatorcontrib><creatorcontrib>Lin, W.-T.</creatorcontrib><creatorcontrib>Huang, R.-Y.</creatorcontrib><creatorcontrib>Chen, T.-C.</creatorcontrib><creatorcontrib>Huang, S.-H.</creatorcontrib><creatorcontrib>Chang, C.-H.</creatorcontrib><creatorcontrib>Tsai, S.-Y.</creatorcontrib><creatorcontrib>Chiu, H.-W.</creatorcontrib><creatorcontrib>Yeh, G.-C.</creatorcontrib><creatorcontrib>Lin, C.-W.</creatorcontrib><creatorcontrib>Wen, Y.-R.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, M.-L.</au><au>Lin, W.-T.</au><au>Huang, R.-Y.</au><au>Chen, T.-C.</au><au>Huang, S.-H.</au><au>Chang, C.-H.</au><au>Tsai, S.-Y.</au><au>Chiu, H.-W.</au><au>Yeh, G.-C.</au><au>Lin, C.-W.</au><au>Wen, Y.-R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pulsed radiofrequency inhibited activation of spinal mitogen-activated protein kinases and ameliorated early neuropathic pain in rats</atitle><jtitle>European journal of pain</jtitle><addtitle>EJP</addtitle><date>2014-05</date><risdate>2014</risdate><volume>18</volume><issue>5</issue><spage>659</spage><epage>670</epage><pages>659-670</pages><issn>1090-3801</issn><eissn>1532-2149</eissn><abstract>Background Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs). Methods In a rat spinal nerve ligation (SNL) model, a low‐volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p‐ERK and p‐p38, as well as TNF‐α level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immunofluorescence staining. Results We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p‐ERK and p‐p38 in the spinal dorsal horn. PRF significantly attenuated SNL‐induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF‐α in the spinal dorsal horn throughout the course. Conclusions Low‐volt PRF significantly ameliorated SNL‐induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down‐regulating spinal MAPK activations and activation‐mediated cytokine release. We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25493301</pmid><doi>10.1002/j.1532-2149.2013.00419.x</doi><tpages>12</tpages></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Acute Disease
Animals
Behavior, Animal
Disease Models, Animal
Down-Regulation - radiation effects
Enzyme Activation - radiation effects
Ganglia, Spinal - radiation effects
Hyperalgesia - prevention & control
Immunohistochemistry
Ligation
Male
Mitogen-Activated Protein Kinases - metabolism
Neuralgia - enzymology
Neuralgia - therapy
Neuroglia - radiation effects
Nociception - radiation effects
p38 Mitogen-Activated Protein Kinases - metabolism
Pain Measurement
Pulsed Radiofrequency Treatment
Random Allocation
Rats
Rats, Sprague-Dawley
Spinal Nerves - enzymology
Spinal Nerves - injuries
Spinal Nerves - radiation effects
Tumor Necrosis Factor-alpha - metabolism
title Pulsed radiofrequency inhibited activation of spinal mitogen-activated protein kinases and ameliorated early neuropathic pain in rats
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