{"title":"口服吗啡通过不依赖阿片受体的机制诱导脊髓5-羟色胺(5-HT)释放。","authors":"Shingo Nakamura, Shuji Komatsu, Toshihiko Yamada, Hiromi Kitahara, Tatsuo Yamamoto","doi":"10.1002/prp2.1119","DOIUrl":null,"url":null,"abstract":"<p><p>Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The purpose of this study was to define the role and mechanism of spinal 5-HT release induced by oral morphine. We also examined whether persistent pain affected the spinal 5-HT release induced by oral morphine. Spinal 5-HT release was measured using microdialysis of lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone and β-funaltrexamine (β-FNA) were used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, a formalin test was used. At 45 min after oral morphine administration, the formalin test was started and spinal 5-HT release was measured. Oral morphine, but not oral oxycodone, increased 5-HT release at the spinal cord to approximately 4000% of the baseline value. This effect of morphine was not antagonized by either naloxone or β-FNA at a dose that antagonized the antinociceptive effect of morphine. Formalin-induced persistent pain itself had no effect on spinal 5-HT release but enhanced the oral morphine-induced spinal 5-HT release. Oral morphine-induced spinal 5-HT release was not mediated by opioid receptor activation. Spinal 5-HT induced by oral morphine did not play a major role in the antinociceptive effect of morphine in the hot plate test. Persistent pain increased oral morphine-induced spinal 5-HT release.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/dc/PRP2-11-e01119.PMC10366105.pdf","citationCount":"0","resultStr":"{\"title\":\"Oral morphine induces spinal 5-hydroxytryptamine (5-HT) release using an opioid receptor-independent mechanism.\",\"authors\":\"Shingo Nakamura, Shuji Komatsu, Toshihiko Yamada, Hiromi Kitahara, Tatsuo Yamamoto\",\"doi\":\"10.1002/prp2.1119\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The purpose of this study was to define the role and mechanism of spinal 5-HT release induced by oral morphine. We also examined whether persistent pain affected the spinal 5-HT release induced by oral morphine. Spinal 5-HT release was measured using microdialysis of lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone and β-funaltrexamine (β-FNA) were used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, a formalin test was used. At 45 min after oral morphine administration, the formalin test was started and spinal 5-HT release was measured. Oral morphine, but not oral oxycodone, increased 5-HT release at the spinal cord to approximately 4000% of the baseline value. This effect of morphine was not antagonized by either naloxone or β-FNA at a dose that antagonized the antinociceptive effect of morphine. Formalin-induced persistent pain itself had no effect on spinal 5-HT release but enhanced the oral morphine-induced spinal 5-HT release. Oral morphine-induced spinal 5-HT release was not mediated by opioid receptor activation. Spinal 5-HT induced by oral morphine did not play a major role in the antinociceptive effect of morphine in the hot plate test. Persistent pain increased oral morphine-induced spinal 5-HT release.</p>\",\"PeriodicalId\":19948,\"journal\":{\"name\":\"Pharmacology Research & Perspectives\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/dc/PRP2-11-e01119.PMC10366105.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology Research & Perspectives\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/prp2.1119\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology Research & Perspectives","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/prp2.1119","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Oral morphine induces spinal 5-hydroxytryptamine (5-HT) release using an opioid receptor-independent mechanism.
Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The purpose of this study was to define the role and mechanism of spinal 5-HT release induced by oral morphine. We also examined whether persistent pain affected the spinal 5-HT release induced by oral morphine. Spinal 5-HT release was measured using microdialysis of lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone and β-funaltrexamine (β-FNA) were used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, a formalin test was used. At 45 min after oral morphine administration, the formalin test was started and spinal 5-HT release was measured. Oral morphine, but not oral oxycodone, increased 5-HT release at the spinal cord to approximately 4000% of the baseline value. This effect of morphine was not antagonized by either naloxone or β-FNA at a dose that antagonized the antinociceptive effect of morphine. Formalin-induced persistent pain itself had no effect on spinal 5-HT release but enhanced the oral morphine-induced spinal 5-HT release. Oral morphine-induced spinal 5-HT release was not mediated by opioid receptor activation. Spinal 5-HT induced by oral morphine did not play a major role in the antinociceptive effect of morphine in the hot plate test. Persistent pain increased oral morphine-induced spinal 5-HT release.
期刊介绍:
PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS