This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Lin, C.-R. Articles by Cheng, J.-T. Search for Related Content PubMed PubMed Citation Articles by Lin, C.-R. Articles by Cheng, J.-T. Related Collections Regional Anesthesia Pain Pharmacology

---

PAIN MEDICINE

Antinociceptive Potentiation and Attenuation of Tolerance by Intrathecal Electric Stimulation in Rats

Chung-Ren Lin, MD PhD^*,, Lin-Cheng Yang, MD, Huey-Ling You, MS^*, Chien-Te Lee, MD, Ming-Hong Tai, PhD, Ping-Heng Tan, MD, Ming-Wei Lin, MS, and Jiin-Tsuey Cheng, PhD^*

*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

Address correspondence and reprint requests to Jiin-Tsuey Cheng, PhD, Department of Biological Sciences, National Sun Yat-Sen University, 70 Lien-Hai Rd., Kaohsiung, Taiwan 804. Address e-mail to tusya{at}mail.nsysu.edu.tw

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.

IMPLICATIONS: 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.