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Oral morphine induces spinal 5-hydroxytryptamine (5-HT) release using an opioid receptor-independent mechanism.
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  • Shingo Nakamura,
  • Shuji Komatsu,
  • Toshihiko Yamada,
  • TATSUO YAMAMOTO
Shingo Nakamura
Kumamoto University Hospital
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Shuji Komatsu
Kumamoto University Hospital
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Toshihiko Yamada
Kumamoto University Hospital
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TATSUO YAMAMOTO
Kumamoto University Hospital

Corresponding Author:[email protected]

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Abstract

Background and Purpose Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of this release is unclear. 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 oral morphine-induced spinal release of 5-HT. Experimental Approach Spinal 5-HT release was measured using microdialysis in lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone was used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, the formalin test was used. Forty-five minutes after oral morphine, the formalin test was started and spinal 5-HT release was measured. Key Results Oral morphine, but not oral oxycodone, increased 5-HT release in the spinal cord to approximately 4,000% of the baseline value, and this effect of morphine was not antagonised by naloxone at the dose that antagonised the analgesic 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. Conclusion and Implications Oral morphine-induced spinal 5-HT release is not mediated by opioid receptor activation. Spinal 5-HT release induced by oral morphine does not play an important role in the analgesic effect of morphine. Persistent pain increases oral morphine-induced spinal 5-HT release.