Low-dose intrathecal naloxone to enhance intrathecal morphine analgesia: A case report

Scott Hamann, MD, PhD; Paul Alexander Sloan, MD; William Witt, MD

doi:10.5055/jom.2008.0028

Authors

Scott Hamann, MD, PhD
Paul Alexander Sloan, MD
William Witt, MD

DOI:

https://doi.org/10.5055/jom.2008.0028

Keywords:

intrathecal naloxone, intrathecal morphine, analgesia, spinal analgesics

Abstract

Ultra low doses of opioid antagonists such as naloxone block excitatory opioid receptor pathways may paradoxically enhance morphine analgesia. This case study reports safety and efficacy of ultra low-dose intrathecal (IT) naloxone added to IT morphine for the treatment of severe refractory chronic low back pain. A 56-year-old man with a history of severe chronic low back pain (postlaminectomy syndrome) was evaluated. Extensive multidisciplinary therapies had all failed. Initial treatment at our clinic was a lumbar IT trial of morphine (unsuccessful) up to 50 mg/day. We administered an IT bolus of morphine 2 mg combined with IT naloxone of 20 ng with the patient’s consent and approval. The onset of pain relief was within 20 minutes and peaked at 1 hour with a 50 percent reduction in VAS pain score. There were no signs of adverse drug toxicity or hemodynamic compromise. An IT infusion of daily morphine 5 mg and naloxone 50 ng was started. Throughout the 3-year follow-up period, the patient maintained pain reduction of 60 to 80 percent, with a return to daily activities and no further hospitalizations.

Author Biographies

Scott Hamann, MD, PhD

Department of Anesthesiology, University of Kentucky, Lexington, Kentucky.

Paul Alexander Sloan, MD

Department of Anesthesiology, University of Kentucky, Lexington, Kentucky.

William Witt, MD

Department of Anesthesiology, University of Kentucky, Lexington, Kentucky.

References

Sloan PA, Kancharla A: Treatment of neuropathic pain with gabapentin. J Pain Palliative Care Pharm. 2003; 17: 89-94.

Sloan PA: Neuraxial pain relief for intractable cancer pain. Curr Pain Headache Rep. 2007; 11:283-289.

Sloan PA, Hamann SR: Ultra low-dose opioid antagonists to enhance opioid analgesia. J Opioid Manage. 2006; 2: 295-304.

Hamann SR, Martin WR: Hyperalgesic and analgesic actions of morphine, U50-488, naltrexone and (−)-lobeline in the rat brain stem. Pharmacol Biochem Behav. 1994; 47: 197-201.

Lasagna L, Beecher HK: The analgesic effectiveness of nalorphine and nalorphine-morphine combinations in man. J Pharmacol Exp Ther. 1954; 112: 356-363.

Wang HY, Friedman E, Olmstead MC, et al.: Ultra-low dose naloxone suppresses opioid tolerance, dependence and associated changes in mu opioid receptor-G protein coupling and GBY signalling. Neuroscience. 2005; 135: 247-261.

Hamann SR, Martin WR: Opioid and nicotinic analgesic and hyperalgesic loci in the rat brain stem. J Pharmacol Exp Ther. 1992; 261: 707-715.

Hamann SR, Wala EP, Rebel A, et al.: Selective antagonism of opioid excitatory receptor systems: a pilot clinical study demonstrating enhancement of morphine analgesia by low-dose naloxone in female patients undergoing elective abdominal laparotomy. Anesthesiology. 2004; 101: A-387.

Gan TJ, Ginsberg B, Glass PSA, et al.: Opioid-sparing effects of low-dose infusion of naloxone in patient-administered morphine sulphate. Anesthesiology. 1997; 87: 1075-1081.

Hamann SR, Sloan PA: Oral naltrexone to enhance analgesia in patients receiving continuous intrathecal morphine for chronic pain: a randomized, double-blind, prospective pilot study. J Opioid Manage. 2007; 3: 137-144.

Crain SM, Shen KF: Antagonists of excitatory opioid receptor functions enhance morphine’s analgesic potency and attenuate opioid tolerance/dependence liability. Pain. 2000; 84: 121-131.

Shen KF, Crain SM: Antagonists at excitatory opioid receptors on sensory neurons in culture increase potency and specificity of opiate analgesics and attenuate development of tolerance/dependence. Brain Res. 1994; 636: 286-297.

Hamann SR, Malik H, Sloan JW, et al.: Interactions of “ultralow” doses of naltrexone and morphine in mature and young male and female rats. Receptor Channels. 2004; 10: 73-81.

Narita M, Imai S, Yajima Y, et al.: Possible involvement of mu1-opioid receptors in the fentanyl- or morphine-induced antinociception at supraspinal and spinal sites. Life Sci. 2002; 70: 2341-2354.

Lunzer MM, Yekkirala A, Hebbel RP, et al.: Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia. Proc Natl Acad Sci USA. 2007; 104: 6061-6065.

Wu HE, Sun HS, Cheng CW, et al.: D-Naloxone or L-naloxone reverses the attenuation of morphine antinociception induced by lipopolysaccharide in the mouse spinal cord via a non-opioid mechanism. Eur J Neurosci. 2006; 24: 2575-2580.

Do Ouro S, Esteban S, Sibirceva U, et al.: Safety and tolerability of high doses of intrathecal fentanyl for the treatment of chronic pain. J Opioid Manage. 2006; 2: 365-368.

Cruciani RA, Arbuck DM: Ultra-low dose oral naltrexone decreases side effects and potentiates the effect of methadone. J Pain Symptom Manage. 2003; 25: 491-494.

Tsai RY, Jang FL, Tai YH, et al.: Ultra-low-dose naloxone restores the antinociceptive effect of morphine and suppresses spinal neuroinflammation in PTX-treated rats. Neuropsychopharmacology. 2008 (in press).

Milne B, Jhamandas K: Naloxone: New therapeutic roles. Can Anaesth Soc J. 1984; 31: 272-278.

Fishman J, Hahn EF, Norton BI, et al.: Preparation and evaluation of a sustained naloxone delivery system in rats. Pharmacology. 1975; 13: 513-519.

Panchagnula R, Bokalial R, Sharma P, Khandavilli S: Transdermal delivery of naloxone: Skin permeation, pharmacokinetic, irritancy and stability studies. Int J Pharm. 2005; 293: 213-223.

Lenton S, Hargreaves K: A trial of naloxone for peer administration has merit, but will the lawyers let it happen? Drug Alcohol Rev. 2000; 19: 365-369.