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


CONCLUSIONS
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.
Lin
Chung-Ren
CR
*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.
Yang
Lin-Cheng
LC
You
Huey-Ling
HL
Lee
Chien-Te
CT
Tai
Ming-Hong
MH
Tan
Ping-Heng
PH
Lin
Ming-Wei
MW
Cheng
Jiin-Tsuey
JT
D000596:Amino Acids / Q000378:metabolism; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004599:Electric Stimulation Therapy; D007278:Injections, Spinal; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D059408:Pain Management; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D000596:Amino Acids; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine