Original Report| Volume 12, ISSUE 2, P213-221, February 2011

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Reduced Analgesic Effect of Acupuncture-like TENS but Not Conventional TENS in Opioid-Treated Patients

Published:September 27, 2010DOI:


      Evidence from recent animal studies indicates that the analgesic effect of low-frequency transcutaneous electrical nerve stimulation (TENS) is reduced in opioid-tolerant animals. The aim of the present study was to compare the analgesic effect of conventional (high frequency) and acupuncture-like (low frequency) TENS between a group of opioid-treated patients and a group of opioid-naive patients in order to determine if this cross-tolerance effect is also present in humans. Twenty-three chronic pain patients (11 who took opioids and 12 who did not) participated in the study. Participants were assigned in a randomized crossover design to receive alternately conventional and acupuncture-like TENS. There was a significant reduction in pain during and after conventional TENS when compared to baseline for both the opioid and nonopioid group (P < .01). For acupuncture-like TENS however, the analgesic effect of TENS was only observed in the nonopioid group (P < .01), with opioid-treated patients showing no change in pain scores during and after TENS when compared to baseline (P > .09). The reduced analgesic effect of acupuncture-like TENS in opioid-treated patients is coherent with previous animal studies and suggests that conventional TENS should be preferred in patients taking opioids on a regular basis.


      This study shows that patients taking opioids on a regular basis are less susceptible to benefit from acupuncture-like TENS. This phenomenon is probably attributable to the fact that the analgesia induced by acupuncture-like TENS and opioids are mediated by the same receptors (ie, μ opioid receptors).

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        • Abram S.E.
        • Reynolds A.C.
        • Cusick J.F.
        Failure of naloxone to reverse analgesia from transcutaneous electrical stimulation in patients with chronic pain.
        Anesth Analg. 1981; 60: 81-84
        • Apkarian A.V.
        • Bushnell M.C.
        • Treede R.D.
        • Zubieta J.K.
        Human brain mechanisms of pain perception and regulation in health and disease.
        Eur J Pain. 2005; 9: 463-484
        • Benedetti F.
        The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia.
        Pain. 1996; 64: 535-543
        • Brennum J.
        • Arendt-Nielsen L.
        • Horn A.
        • Secher N.H.
        • Jensen T.S.
        Quantitative sensory examination during epidural anaesthesia and analgesia in man: Effects of morphine.
        Pain. 1993; 52: 75-83
        • Bruehl S.
        • Chung O.Y.
        • Ward P.
        • Johnson B.
        • McCubbin J.A.
        The relationship between resting blood pressure and acute pain sensitivity in healthy normotensives and chronic back pain sufferers: The effects of opioid blockade.
        Pain. 2002; 100: 191-201
        • Celada P.
        • Puig M.
        • Amargos-Bosch M.
        • Adell A.
        • Artigas F.
        The therapeutic role of 5-HT1A and 5-HT2A receptors in depression.
        J Psychiatry Neurosci. 2004; 29: 252-265
        • Chandran P.
        • Sluka K.A.
        Development of opioid tolerance with repeated transcutaneous electrical nerve stimulation administration.
        Pain. 2003; 102: 195-201
        • Chapman C.R.
        • Benedetti C.
        Analgesia following transcutaneous electrical stimulation and its partial reversal by a narcotic antagonist.
        Life Sci. 1977; 21: 1645-1648
        • Charron J.
        • Rainville P.
        • Marchand S.
        Direct comparison of placebo effects on clinical and experimental pain.
        Clin J Pain. 2006; 22: 204-211
        • Chen C.C.
        • Johnson M.I.
        An investigation into the hypoalgesic effects of high- and low-frequency transcutaneous electrical nerve stimulation (TENS) on experimentally-induced blunt pressure pain in healthy human participants.
        J Pain. 2010; 11: 53-61
        • Dworkin R.H.
        • Turk D.C.
        • Farrar J.T.
        • Haythornthwaite J.A.
        • Jensen M.P.
        • Katz N.P.
        • Kerns R.D.
        • Stucki G.
        • Allen R.R.
        • Bellamy N.
        • Carr D.B.
        • Chandler J.
        • Cowan P.
        • Dionne R.
        • Galer B.S.
        • Hertz S.
        • Jadad A.R.
        • Kramer L.D.
        • Manning D.C.
        • Martin S.
        • McCormick C.G.
        • McDermott M.P.
        • McGrath P.
        • Quessy S.
        • Rappaport B.A.
        • Robbins W.
        • Robinson J.P.
        • Rothman M.
        • Royal M.A.
        • Simon L.
        • Stauffer J.W.
        • Stein W.
        • Tollett J.
        • Wernicke J.
        • Witter J.
        Core outcome measures for chronic pain clinical trials: IMMPACT recommendations.
        Pain. 2005; 113: 9-19
        • Facchinetti F.
        • Sandrini G.
        • Petraglia F.
        • Alfonsi E.
        • Nappi G.
        • Genazzani A.R.
        Concomitant increase in nociceptive flexion reflex threshold and plasma opioids following transcutaneous nerve stimulation.
        Pain. 1984; 19: 295-303
        • Fishbain D.A.
        • Chabal C.
        • Abbott A.
        • Heine L.W.
        • Cutler R.
        Transcutaneous electrical nerve stimulation (TENS) treatment outcome in long-term users.
        Clin J Pain. 1996; 12: 201-214
        • Foley R.A.
        Transcutaneous electrical nerve stimulation.
        in: Hayes K.W. Manual for Physical Agents. 5th ed. Prentice Hall Health, Englewood Cliffs, NJ2000: 121-147
        • Freeman T.B.
        • Campbell J.N.
        • Long D.M.
        Naloxone does not affect pain relief induced by electrical stimulation in man.
        Pain. 1983; 17: 189-195
        • Glynn C.J.
        • Mather L.E.
        • Cousins M.J.
        • Graham J.R.
        • Wilson P.R.
        Peridural meperidine in humans: Analgesic response, pharmacokinetics, and transmission into CSF.
        Anesthesiology. 1981; 55: 520-526
        • Gourlay G.K.
        Advances in opioid pharmacology.
        Support Care Cancer. 2005; 13: 153-159
      1. Guy W: ECDEU Assessment Manual for Psychopharmacology (DHEW Publication No. ADM 76-338), Government Printing Office, Washington DC, 1976

        • Hansson P.
        • Ekblom A.
        • Thomsson M.
        • Fjellner B.
        Influence of naloxone on relief of acute oro-facial pain by transcutaneous electrical nerve stimulation (TENS) or vibration.
        Pain. 1986; 24: 323-329
        • Kalra A.
        • Urban M.O.
        • Sluka K.A.
        Blockade of opioid receptors in rostral ventral medulla prevents antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS).
        J Pharmacol Exp Ther. 2001; 298: 257-263
        • Kalso E.A.
        • Sullivan A.F.
        • McQuay H.J.
        • Dickenson A.H.
        • Roques B.P.
        Cross-tolerance between mu opioid and alpha-2 adrenergic receptors, but not between mu and delta opioid receptors in the spinal cord of the rat.
        J Pharmacol Exp Ther. 1993; 265: 551-558
        • Le Bars D.
        • Willer J.C.
        • De B.T.
        Morphine blocks descending pain inhibitory controls in humans.
        Pain. 1992; 48: 13-20
        • Leonard G.
        • Rodrigue M.
        • Cloutier C.
        • Marchand S.
        Deciphering the role of endogenous opioids in high frequency TENS using high and low doses of naloxone.
        IASP 12th World Congress on Pain (Glasgow). 2008;
        • Lundeberg T.
        • Bondesson L.
        • Lundstrom V.
        Relief of primary dysmenorrhea by transcutaneous electrical nerve stimulation.
        Acta Obstet Gynecol Scand. 1985; 64: 491-497
      2. Lundy-Ekman L: Somatosensory system, in (ed): Neuroscience: Fundamentals for Rehabilitation, 1st ed. Philadelphia, PA, W.B. Saunders Company, 1998, pp 85-105

        • Magora F.
        • Olshwang D.
        • Eimerl D.
        • Shorr J.
        • Katzenelson R.
        • Cotev S.
        • Davidson J.T.
        Observations on extradural morphine analgesia in various pain conditions.
        Br J Anaesth. 1980; 52: 247-252
        • Melzack R.
        • Wall P.D.
        Pain mechanisms: A new theory.
        Science. 1965; 150: 971-979
        • Meyer J.H.
        Imaging the serotonin transporter during major depressive disorder and antidepressant treatment.
        J Psychiatry Neurosci. 2007; 32: 86-102
        • Millan M.J.
        Descending control of pain.
        Prog Neurobiol. 2002; 66: 355-474
        • O’Sullivan S.B.
        • Schmitz T.J.
        Physical Rehabilitation: Assessment and Treatment.
        4th ed. F.A. Davis Company, Philadelphia, PA2000
        • Park R.
        • Wallace M.S.
        • Schulteis G.
        Relative sensitivity to alfentanil and reliability of current perception threshold vs von Frey tactile stimulation and thermal sensory testing.
        J Peripher Nerv Syst. 2001; 6: 232-240
        • Price D.D.
        • McGrath P.A.
        • Rafii A.
        • Buckingham B.
        The validation of visual analogue scales as ratio scale measures for chronic and experimental pain.
        Pain. 1983; 17: 45-56
        • Ram K.C.
        • Eisenberg E.
        • Haddad M.
        • Pud D.
        Oral opioid use alters DNIC but not cold pain perception in patients with chronic pain - new perspective of opioid-induced hyperalgesia.
        Pain. 2008; 139: 431-438
        • Robinson A.J.
        • Snyder-Mackler L.
        Clinical Electrophysiology: Electrotherapy and Electrophysiologic Testing.
        3rd ed. Lippincott Williams & Wilkins, Philadelphia, PA2007
        • Sasaki A.
        • Nakashima Y.
        • Takasaki I.
        • Andoh T.
        • Shiraki K.
        • Kuraishi Y.
        Morphine inhibits herpetic allodynia through mu-opioid receptors induced in Abeta-fiber neurons.
        Neuroreport. 2008; 19: 975-979
        • Schug S.
        • Gandham N.
        Opioids: Clinical use.
        in: McMahon S.B. Koltzenburg M. Wall and Melzack’s Textbook of Pain. 5th ed. Elsevier Churchill Livingstone, China, Beijing, CN2006: 443-457
        • Sjolund B.
        • Terenius L.
        • Eriksson M.
        Increased cerebrospinal fluid levels of endorphins after electro-acupuncture.
        Acta Physiol Scand. 1977; 100: 382-384
        • Sluka K.A.
        • Deacon M.
        • Stibal A.
        • Strissel S.
        • Terpstra A.
        Spinal blockade of opioid receptors prevents the analgesia produced by TENS in arthritic rats.
        J Pharmacol Exp Ther. 1999; 289: 840-846
        • Sluka K.A.
        • Judge M.A.
        • McColley M.M.
        • Reveiz P.M.
        • Taylor B.M.
        Low frequency TENS is less effective than high frequency TENS at reducing inflammation-induced hyperalgesia in morphine-tolerant rats.
        Eur J Pain. 2000; 4: 185-193
        • Sluka K.A.
        • Walsh D.
        Transcutaneous electrical nerve stimulation: Basic science mechanisms and clinical effectiveness.
        J Pain. 2003; 4: 109-121
        • Solomon R.A.
        • Viernstein M.C.
        • Long D.M.
        Reduction of postoperative pain and narcotic use by transcutaneous electrical nerve stimulation.
        Surgery. 1980; 87: 142-146
        • Warke K.
        • Al-Smadi J.
        • Baxter D.
        • Walsh D.M.
        • Lowe-Strong A.S.
        Efficacy of transcutaneous electrical nerve stimulation (tens) for chronic low-back pain in a multiple sclerosis population: A randomized, placebo-controlled clinical trial.
        Clin J Pain. 2006; 22: 812-819
        • Willer J.C.
        • Bouhassira D.
        • Le B.D.
        Neurophysiological bases of the counterirritation phenomenon: Diffuse control inhibitors induced by nociceptive stimulation.
        Neurophysiol Clin. 1999; 29: 379-400
        • Willer J.C.
        • Roby A.
        • Boulu P.
        • Boureau F.
        Comparative effects of electroacupuncture and transcutaneous nerve stimulation on the human blink reflex.
        Pain. 1982; 14: 267-278
        • Yamamoto J.
        • Kawamata T.
        • Niiyama Y.
        • Omote K.
        • Namiki A.
        Down-regulation of mu opioid receptor expression within distinct subpopulations of dorsal root ganglion neurons in a murine model of bone cancer pain.
        Neuroscience. 2008; 151: 843-853