Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain
Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from...
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| Veröffentlicht in: | Journal of neurophysiology 2017-08, Vol.118 (2), p.1321-1328 |
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| creator | Liu, Cui-Cui Zhang, Xin-Sheng Ruan, Yu-Ting Huang, Zhu-Xi Zhang, Su-Bo Liu, Meng Luo, Hai-Jie Wu, Shao-Ling Ma, Chao |
| description | Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons ( |
| doi_str_mv | 10.1152/jn.00745.2016 |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5558033</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1910336993</sourcerecordid><originalsourceid>FETCH-LOGICAL-c387t-8d953a0583617843bedd9878219539ed27dfebe4a75a48abacb9970c43b0561b3</originalsourceid><addsrcrecordid>eNpVkUFvFCEUx4mxsdvq0avh6GVWGJaBuZg0ra0mTUwaPRMG3nZZGRiB2bhfpZ-2bLc2eoK893u_95I_Qu8pWVLK20_bsCRErPiyJbR7hRa11jaU9_I1WhBS_4wIcYrOct6SCnLSvkGnrewoZ0ws0MOFMfM4e11cDDiu8Qhls_f3fh__aI9dMAl0hozLBrC2Ox0MWFzb5jgBwTZTinY2BXvYgc91Bl_d3WAdLDYxlOSGuRwEEft5HHTC1uVfeAMpuCdH40Idr9YJUna5QCh40i68RSdr7TO8e37P0c_rLz8uvza332--XV7cNoZJURppe8404ZJ1VMgVG8DaXgrZ0lrvwbbCrmGAlRZcr6QetBn6XhBTScI7OrBz9PnoneZhBGvq_qS9mpIbddqrqJ36vxPcRt3HneKcS8JYFXx8FqT4e4Zc1OiyAe91gDhnRXtasa7vD2hzRE2KOSdYv6yhRB3yVNugnvJUhzwr_-Hf217ovwGyR1-boJw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1910336993</pqid></control><display><type>article</type><title>Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain</title><source>MEDLINE</source><source>American Physiological Society</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Liu, Cui-Cui ; Zhang, Xin-Sheng ; Ruan, Yu-Ting ; Huang, Zhu-Xi ; Zhang, Su-Bo ; Liu, Meng ; Luo, Hai-Jie ; Wu, Shao-Ling ; Ma, Chao</creator><creatorcontrib>Liu, Cui-Cui ; Zhang, Xin-Sheng ; Ruan, Yu-Ting ; Huang, Zhu-Xi ; Zhang, Su-Bo ; Liu, Meng ; Luo, Hai-Jie ; Wu, Shao-Ling ; Ma, Chao</creatorcontrib><description>Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain.
Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain.</description><identifier>ISSN: 0022-3077</identifier><identifier>EISSN: 1522-1598</identifier><identifier>DOI: 10.1152/jn.00745.2016</identifier><identifier>PMID: 28615337</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Animals ; Ganglia, Spinal - metabolism ; Glycation End Products, Advanced - metabolism ; Humans ; Intervertebral Disc Displacement - complications ; Intervertebral Disc Displacement - metabolism ; Low Back Pain - etiology ; Low Back Pain - metabolism ; Lumbosacral Region - pathology ; Male ; Pyruvaldehyde - metabolism ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Journal of neurophysiology, 2017-08, Vol.118 (2), p.1321-1328</ispartof><rights>Copyright © 2017 the American Physiological Society.</rights><rights>Copyright © 2017 the American Physiological Society 2017 American Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-8d953a0583617843bedd9878219539ed27dfebe4a75a48abacb9970c43b0561b3</citedby><cites>FETCH-LOGICAL-c387t-8d953a0583617843bedd9878219539ed27dfebe4a75a48abacb9970c43b0561b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28615337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Cui-Cui</creatorcontrib><creatorcontrib>Zhang, Xin-Sheng</creatorcontrib><creatorcontrib>Ruan, Yu-Ting</creatorcontrib><creatorcontrib>Huang, Zhu-Xi</creatorcontrib><creatorcontrib>Zhang, Su-Bo</creatorcontrib><creatorcontrib>Liu, Meng</creatorcontrib><creatorcontrib>Luo, Hai-Jie</creatorcontrib><creatorcontrib>Wu, Shao-Ling</creatorcontrib><creatorcontrib>Ma, Chao</creatorcontrib><title>Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain</title><title>Journal of neurophysiology</title><addtitle>J Neurophysiol</addtitle><description>Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain.
Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain.</description><subject>Animals</subject><subject>Ganglia, Spinal - metabolism</subject><subject>Glycation End Products, Advanced - metabolism</subject><subject>Humans</subject><subject>Intervertebral Disc Displacement - complications</subject><subject>Intervertebral Disc Displacement - metabolism</subject><subject>Low Back Pain - etiology</subject><subject>Low Back Pain - metabolism</subject><subject>Lumbosacral Region - pathology</subject><subject>Male</subject><subject>Pyruvaldehyde - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0022-3077</issn><issn>1522-1598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUFvFCEUx4mxsdvq0avh6GVWGJaBuZg0ra0mTUwaPRMG3nZZGRiB2bhfpZ-2bLc2eoK893u_95I_Qu8pWVLK20_bsCRErPiyJbR7hRa11jaU9_I1WhBS_4wIcYrOct6SCnLSvkGnrewoZ0ws0MOFMfM4e11cDDiu8Qhls_f3fh__aI9dMAl0hozLBrC2Ox0MWFzb5jgBwTZTinY2BXvYgc91Bl_d3WAdLDYxlOSGuRwEEft5HHTC1uVfeAMpuCdH40Idr9YJUna5QCh40i68RSdr7TO8e37P0c_rLz8uvza332--XV7cNoZJURppe8404ZJ1VMgVG8DaXgrZ0lrvwbbCrmGAlRZcr6QetBn6XhBTScI7OrBz9PnoneZhBGvq_qS9mpIbddqrqJ36vxPcRt3HneKcS8JYFXx8FqT4e4Zc1OiyAe91gDhnRXtasa7vD2hzRE2KOSdYv6yhRB3yVNugnvJUhzwr_-Hf217ovwGyR1-boJw</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Liu, Cui-Cui</creator><creator>Zhang, Xin-Sheng</creator><creator>Ruan, Yu-Ting</creator><creator>Huang, Zhu-Xi</creator><creator>Zhang, Su-Bo</creator><creator>Liu, Meng</creator><creator>Luo, Hai-Jie</creator><creator>Wu, Shao-Ling</creator><creator>Ma, Chao</creator><general>American Physiological Society</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170801</creationdate><title>Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain</title><author>Liu, Cui-Cui ; Zhang, Xin-Sheng ; Ruan, Yu-Ting ; Huang, Zhu-Xi ; Zhang, Su-Bo ; Liu, Meng ; Luo, Hai-Jie ; Wu, Shao-Ling ; Ma, Chao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-8d953a0583617843bedd9878219539ed27dfebe4a75a48abacb9970c43b0561b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Ganglia, Spinal - metabolism</topic><topic>Glycation End Products, Advanced - metabolism</topic><topic>Humans</topic><topic>Intervertebral Disc Displacement - complications</topic><topic>Intervertebral Disc Displacement - metabolism</topic><topic>Low Back Pain - etiology</topic><topic>Low Back Pain - metabolism</topic><topic>Lumbosacral Region - pathology</topic><topic>Male</topic><topic>Pyruvaldehyde - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Cui-Cui</creatorcontrib><creatorcontrib>Zhang, Xin-Sheng</creatorcontrib><creatorcontrib>Ruan, Yu-Ting</creatorcontrib><creatorcontrib>Huang, Zhu-Xi</creatorcontrib><creatorcontrib>Zhang, Su-Bo</creatorcontrib><creatorcontrib>Liu, Meng</creatorcontrib><creatorcontrib>Luo, Hai-Jie</creatorcontrib><creatorcontrib>Wu, Shao-Ling</creatorcontrib><creatorcontrib>Ma, Chao</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neurophysiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Cui-Cui</au><au>Zhang, Xin-Sheng</au><au>Ruan, Yu-Ting</au><au>Huang, Zhu-Xi</au><au>Zhang, Su-Bo</au><au>Liu, Meng</au><au>Luo, Hai-Jie</au><au>Wu, Shao-Ling</au><au>Ma, Chao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain</atitle><jtitle>Journal of neurophysiology</jtitle><addtitle>J Neurophysiol</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>118</volume><issue>2</issue><spage>1321</spage><epage>1328</epage><pages>1321-1328</pages><issn>0022-3077</issn><eissn>1522-1598</eissn><abstract>Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 μm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain.
Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>28615337</pmid><doi>10.1152/jn.00745.2016</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Ganglia, Spinal - metabolism Glycation End Products, Advanced - metabolism Humans Intervertebral Disc Displacement - complications Intervertebral Disc Displacement - metabolism Low Back Pain - etiology Low Back Pain - metabolism Lumbosacral Region - pathology Male Pyruvaldehyde - metabolism Rats Rats, Sprague-Dawley |
| title | Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain |
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