2009 Fiscal Year Final Research Report
Evaluation of spinal mechanism of opioid-induced hyperalgesia
| Project/Area Number |
20890132
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| Research Category |
Grant-in-Aid for Young Scientists (Start-up)
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| Allocation Type | Single-year Grants |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Shimane University |
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Principal Investigator |
ISHIDA Ryosuke Shimane University, 医学部, 医科医員 (50508934)
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| Project Period (FY) |
2008 – 2009
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| Keywords | レミフェンタニル / オピオイド誘発性痛覚過敏 / μオピオイド受容体 / ERK |
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| Research Abstract |
Recent studies suggest that remifentanil may induce hyperalgesia as with other μ-opioid agonists. However, its mechanism is still unclear. We performed animal experiments to investigate whether intravenous infusion of remifentanil induces hyperalgesia and in what situation this phenomenon occurs, furthermore, whether remifentanil-induced hyperalgesia is related to activation of ERK1/2 (extracellular signal-regulated protein kinase 1/2) pathway.
Remifentanil was administered through a catheter cannulated in tail vein of rat. After termination of drug administration, tail-flick test was performed followed by immunohistochemistry. Furthermore, we examined whether intrathecal pre-administration of MEK (MAPK/ERK kinase) inhibitor, U0126, can suppress hyperalgesia. As a result, remifentanil showed anti-nociceptive effect in the dose dependent manner in rats. Thirty minutes infusion of remifentanil did not induce hyperalgesia. However, the tail-flick latency after termination of infusion was significantly shorter in all remifentanil 120min groups than control group regardless of dose. Significantly more p-ERK positive neurons located in spinal dorsal horn were observed in remifentanil 120min group with hyperalgesia than in remifentanil 30min group without hyperalgesia. However, U0126 could not suppress the occurrence of hyperalgesia. In conclusion, remifentanil induces hyperalgesia depend on its duration of administration. Although, ERK1/2 pathway is related to remifentanil-induced hyperalgesia, it may not be caused by a single factor. Because inhibition of ERK1/2 phosphorylation could not prevent hyperalgesia.
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