Songyi Zhou, Yizhao Pan, Yan Zhang, Lijun Gu, Leikai Ma, Qingqing Xu, Weijian Wang, Jiehao Sun
{"title":"抗动力蛋白1的反义寡脱氧核苷酸通过调节大鼠脊髓n-甲基- d -天冬氨酸受体表达减少瑞芬太尼诱导的痛觉过敏。","authors":"Songyi Zhou, Yizhao Pan, Yan Zhang, Lijun Gu, Leikai Ma, Qingqing Xu, Weijian Wang, Jiehao Sun","doi":"10.3344/kjp.22398","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Spinal N-methyl-D-aspartate (NMDA) receptor activation is attributed to remifentanil-induced hyperalgesia (RIH). However, the specific mechanism and subsequent treatment is still unknown. Previous studies have shown that the dynamin-related protein 1 (DRP1)-mitochondria-reactive oxygen species (ROS) pathway plays an important role in neuropathic pain. This study examined whether antisense oligodeoxynucleotides against DRP1 (AS-DRP1) could reverse RIH.</p><p><strong>Methods: </strong>The authors first measured changes in paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) at 24 hours before remifentanil infusion and 4, 8, 24, and 48 hours after infusion. The expression levels of DRP1 and NR<sub>2</sub>B were measured after behavioral testing using Western blotting. In addition, DRP1 expression was knocked down by intrathecal administration of AS-DRP1 to investigate the effects of DRP1 on RIH. The behavioral testing, the expression levels of spinal DRP1 and NR<sub>2</sub>B, and dorsal mitochondrial superoxide were measured. Changes in mitochondrial morphology were assessed using electron microscopy.</p><p><strong>Results: </strong>After remifentanil exposure, upregulation of spinal DRP1 and NR<sub>2</sub>B was observed along with a reduction in PWMT and PWTL. In addition, AS-DRP1 improved RIH-induced PWTL and PWMT (<i>P</i> < 0.001 and <i>P</i> < 0.001) and reduced remifentanil-mediated enhancement of spinal DRP1 and NR<sub>2</sub>B expression (<i>P</i> = 0.020 and <i>P</i> = 0.022). More importantly, AS-DRP1 reversed RIH-induced mitochondrial fission (<i>P</i> = 0.020) and mitochondrial superoxide upregulation (<i>P</i> = 0.031).</p><p><strong>Conclusions: </strong>These results indicate that AS-DRP1 could modulate NMDA receptor expression to prevent RIH through the DRP1-mitochondria-ROS pathway.</p>","PeriodicalId":56252,"journal":{"name":"Korean Journal of Pain","volume":"36 3","pages":"316-327"},"PeriodicalIF":3.4000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/38/kjp-36-3-316.PMC10322665.pdf","citationCount":"0","resultStr":"{\"title\":\"Antisense oligodeoxynucleotides against dynamin-related protein 1 reduce remifentanil-induced hyperalgesia by modulating spinal N-methyl-D-aspartate receptor expression in rats.\",\"authors\":\"Songyi Zhou, Yizhao Pan, Yan Zhang, Lijun Gu, Leikai Ma, Qingqing Xu, Weijian Wang, Jiehao Sun\",\"doi\":\"10.3344/kjp.22398\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Spinal N-methyl-D-aspartate (NMDA) receptor activation is attributed to remifentanil-induced hyperalgesia (RIH). However, the specific mechanism and subsequent treatment is still unknown. Previous studies have shown that the dynamin-related protein 1 (DRP1)-mitochondria-reactive oxygen species (ROS) pathway plays an important role in neuropathic pain. This study examined whether antisense oligodeoxynucleotides against DRP1 (AS-DRP1) could reverse RIH.</p><p><strong>Methods: </strong>The authors first measured changes in paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) at 24 hours before remifentanil infusion and 4, 8, 24, and 48 hours after infusion. The expression levels of DRP1 and NR<sub>2</sub>B were measured after behavioral testing using Western blotting. In addition, DRP1 expression was knocked down by intrathecal administration of AS-DRP1 to investigate the effects of DRP1 on RIH. The behavioral testing, the expression levels of spinal DRP1 and NR<sub>2</sub>B, and dorsal mitochondrial superoxide were measured. Changes in mitochondrial morphology were assessed using electron microscopy.</p><p><strong>Results: </strong>After remifentanil exposure, upregulation of spinal DRP1 and NR<sub>2</sub>B was observed along with a reduction in PWMT and PWTL. In addition, AS-DRP1 improved RIH-induced PWTL and PWMT (<i>P</i> < 0.001 and <i>P</i> < 0.001) and reduced remifentanil-mediated enhancement of spinal DRP1 and NR<sub>2</sub>B expression (<i>P</i> = 0.020 and <i>P</i> = 0.022). More importantly, AS-DRP1 reversed RIH-induced mitochondrial fission (<i>P</i> = 0.020) and mitochondrial superoxide upregulation (<i>P</i> = 0.031).</p><p><strong>Conclusions: </strong>These results indicate that AS-DRP1 could modulate NMDA receptor expression to prevent RIH through the DRP1-mitochondria-ROS pathway.</p>\",\"PeriodicalId\":56252,\"journal\":{\"name\":\"Korean Journal of Pain\",\"volume\":\"36 3\",\"pages\":\"316-327\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/38/kjp-36-3-316.PMC10322665.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Korean Journal of Pain\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3344/kjp.22398\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Korean Journal of Pain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3344/kjp.22398","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Antisense oligodeoxynucleotides against dynamin-related protein 1 reduce remifentanil-induced hyperalgesia by modulating spinal N-methyl-D-aspartate receptor expression in rats.
Background: Spinal N-methyl-D-aspartate (NMDA) receptor activation is attributed to remifentanil-induced hyperalgesia (RIH). However, the specific mechanism and subsequent treatment is still unknown. Previous studies have shown that the dynamin-related protein 1 (DRP1)-mitochondria-reactive oxygen species (ROS) pathway plays an important role in neuropathic pain. This study examined whether antisense oligodeoxynucleotides against DRP1 (AS-DRP1) could reverse RIH.
Methods: The authors first measured changes in paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) at 24 hours before remifentanil infusion and 4, 8, 24, and 48 hours after infusion. The expression levels of DRP1 and NR2B were measured after behavioral testing using Western blotting. In addition, DRP1 expression was knocked down by intrathecal administration of AS-DRP1 to investigate the effects of DRP1 on RIH. The behavioral testing, the expression levels of spinal DRP1 and NR2B, and dorsal mitochondrial superoxide were measured. Changes in mitochondrial morphology were assessed using electron microscopy.
Results: After remifentanil exposure, upregulation of spinal DRP1 and NR2B was observed along with a reduction in PWMT and PWTL. In addition, AS-DRP1 improved RIH-induced PWTL and PWMT (P < 0.001 and P < 0.001) and reduced remifentanil-mediated enhancement of spinal DRP1 and NR2B expression (P = 0.020 and P = 0.022). More importantly, AS-DRP1 reversed RIH-induced mitochondrial fission (P = 0.020) and mitochondrial superoxide upregulation (P = 0.031).
Conclusions: These results indicate that AS-DRP1 could modulate NMDA receptor expression to prevent RIH through the DRP1-mitochondria-ROS pathway.
期刊介绍：
Korean Journal of Pain (Korean J Pain, KJP) is the official journal of the Korean Pain Society, founded in 1986. It has been published since 1988. It publishes peer reviewed original articles related to all aspects of pain, including clinical and basic research, patient care, education, and health policy. It has been published quarterly in English since 2009 (on the first day of January, April, July, and October). In addition, it has also become the official journal of the International Spinal Pain Society since 2016. The mission of the Journal is to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals. The circulation number per issue is 50.
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