Lin Chung-Ren, Yang Lin-Cheng, You Huey-Ling, Lee Chien-Te, Tai Ming-Hong, Tan Ping-Heng, Lin Ming-Wei, Cheng Jiin-Tsuey
*Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; Departments of †Anesthesiology and ‡Nephrology, Kaohsiung Chung Gang Memorial Hospital, Kaohsiung, Taiwan; and §Department of Medical Research, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan.
Anesth Analg. 2003 Jun;96(6):1711-1716. doi: 10.1213/01.ANE.0000061471.11925.73.
We tested whether intrathecal electric stimulation would reduce the tolerance to chronic morphine use and the severity of precipitated morphine withdrawal. Rats received intrathecal electrode catheter implantation and a continuous intrathecal infusion of morphine (2 nmol/h) or saline for 7 days. Intrathecal electric stimulations (0, 20, or 200 V) were performed once daily during the same period. Daily tail-flick and intrathecal morphine challenge tests were performed to assess the effect of intrathecal electric stimulation on antinociception and tolerance to morphine. Naloxone withdrawal (2 mg/kg) was performed to assess morphine dependence, and changes in spinal neurotransmitters were monitored by microdialysis. The antinociceptive effect of intrathecal morphine was increased by 200 V of electric stimulation. The magnitude of tolerance was decreased in the rats receiving the 2 nmol/h infusion with 200 V of intrathecal electric stimulation compared with the control group (morphine 2 nmol/h alone) (AD(50), 13.6 vs 124.7 nmol). The severity of naloxone-induced withdrawal was less in the rats receiving 200 V of stimulation. Intrathecal stimulation thus enhances analgesia and attenuates naloxone-induced withdrawal symptoms in rats receiving chronic intrathecal morphine infusion. Increases in spinal glycine release may be the underlying mechanism. This method may merit further investigation in the context of the long-term use of intrathecal opioids for controlling chronic pain.
Control of chronic pain is a major health problem. We show here that direct electrical stimulation of the spinal cord in rats enhances analgesia and attenuates naloxone-induced withdrawal symptoms. This may warrant further investigation in the context of long-term use of intrathecal opioids for controlling chronic pain.
我们测试了鞘内电刺激是否会降低对慢性吗啡使用的耐受性以及戒断吗啡时的严重程度。大鼠接受鞘内电极导管植入，并连续7天鞘内输注吗啡（2纳摩尔/小时）或生理盐水。在此期间，每天进行一次鞘内电刺激（0、20或200伏）。每天进行甩尾和鞘内吗啡激发试验，以评估鞘内电刺激对镇痛作用和吗啡耐受性的影响。进行纳洛酮戒断（2毫克/千克）以评估吗啡依赖性，并通过微透析监测脊髓神经递质的变化。200伏的电刺激增强了鞘内吗啡的镇痛作用。与对照组（仅吗啡2纳摩尔/小时）相比，接受2纳摩尔/小时输注并伴有200伏鞘内电刺激的大鼠耐受性程度降低（半数有效剂量，13.6对124.7纳摩尔）。接受200伏刺激的大鼠中，纳洛酮诱发的戒断严重程度较轻。因此，鞘内刺激可增强接受慢性鞘内吗啡输注大鼠的镇痛作用，并减轻纳洛酮诱发的戒断症状。脊髓甘氨酸释放增加可能是其潜在机制。在长期使用鞘内阿片类药物控制慢性疼痛的背景下，这种方法可能值得进一步研究。
慢性疼痛的控制是一个主要的健康问题。我们在此表明，对大鼠脊髓进行直接电刺激可增强镇痛作用，并减轻纳洛酮诱发的戒断症状。在长期使用鞘内阿片类药物控制慢性疼痛的背景下，这可能值得进一步研究。
