Antinociceptive potentiation and attenuation of tolerance by intrathecal electric stimulation in rats

Chung Ren Lin, Lin Cheng Yang, Huey Ling You, Chien Te Lee, Ming Hong Tai, Ping Heng Tan, Ming Wei Lin, Jiin Tsuey Cheng

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


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) (AD50, 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.

Original languageEnglish
Pages (from-to)1711-1716
Number of pages6
JournalAnesthesia and analgesia
Issue number6
Publication statusPublished - 2003 Jun 1

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine


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