Clinical analgesia correlates with decline in temporal summation in response to remifentanil infusion in patients with chronic neuropathic (radicular) pain

Authors

  • Erica Suzan, PhD
  • Ayelet Midbari, MD
  • Dorit Pud, PhD
  • Salim Hadad, PhD
  • Elon Eisenberg, MD

DOI:

https://doi.org/10.5055/jom.2016.0340

Keywords:

neuropathic pain, radicular pain, opioids, remifentanil, temporal summation

Abstract

Background: Animal studies have shown that in addition to their antinociceptive effects, opioids have attenuated the electrophysiological “wind-up” phenomenon. Although effects of opioids on clinical pain and on temporal summation (TS), the human correlatives of this phenomenon, have been tested repeatedly, correlations between these two parameters have not been reported so far.

Objectives: To search for possible correlations between the effects of remifentanil on clinical pain intensity and on the magnitude of TS in patients with chronic pain.

Design: A single-blinded prospective study.

Setting: A tertiary care pain clinic.

Patients: Thirty-one patients (24 men) with chronic lumbar (radicular) neuropathic pain.

Intervention: Intervenous administration of saline followed by remifentanil infusions.

Main Outcome Measures: Clinical pain intensity and thermal TS measured at baseline, during infusion of each drug and 20 minutes after termination of remifentnail infusion.

Results: Friedman test revealed statistically significant differences in the magnitudes of both clinical pain intensity and TS (χ2(3) = 73, p < 0.001 and χ2(3) = 11.38, p = 0.01, respectively). Post hoc analysis (Wilcoxon signed-rank test) showed significant differences between clinical pain intensities measured at all time points but significant reductions in the magnitudes of TS were found only during remifentanil compared to baseline (p = 0.014) and to saline (p = 0.019). The difference in clinical pain between saline and remifentanil positively correlated with the difference in TS measured at the same time points (Spearman's test; r = 0.444, p = 0.012).

Conclusions: These results point to a possible causative relationship between TS and opioid analgesia.

Author Biographies

Erica Suzan, PhD

The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Institute of Pain Medicine, Rambam Health Care Campus, Haifa, Israel

Ayelet Midbari, MD

Institute of Pain Medicine, Rambam Health Care Campus, Haifa, Israel

Dorit Pud, PhD

Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.

Salim Hadad, PhD

Department of Pharmacy, Rambam Health Care Campus, Haifa, Israel

Elon Eisenberg, MD

The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Institute of Pain Medicine, Rambam Health Care Campus, Haifa, Israel

References

Ballantyne JC: Pain medicine: Repairing a fractured dream. Anesthesiology. 2011; 114: 243-246.

Attal N, Bouhassira D: Pharmacotherapy of neuropathic pain: Which drugs, which treatment algorithms? Pain. 2015; 156: 104-114.

Basbaum AI, Fields HL: Endogenous pain control systems: Brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci. 1984; 7: 309-338.

Besson JM, Chaouch A: Peripheral and spinal mechanisms of nociception. Physiol Rev. 1987; 67: 67-186.

Mendell LM: Physiological properties of unmyelinated fiber projection to the spinal cord. Exp Neurol. 1966; 16: 316-332.

Price DD, Hayes RL, Ruda M, et al.: Spatial and temporal transformations of input to spinothalamic tract neurons and their relation to somatic sensations. J Neurophysiol. 1978; 41: 933-947.

Price DD, Mao J, Frenk H, et al.: The N-methyl-D-aspartate receptor antagonist dextromethorphan selectively reduces temporal summation of second pain in man. Pain. 1994; 59: 165–174.

Price DD, Hu JW, Dubner R, et al.: Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain. 1977; 3: 57-68.

Granot M, Granovsky Y, Sprecher E, et al.: Contact heatevoked temporal summation: Tonic versus repetitive-phasic stimulation. Pain. 2006; 122: 295-305.

Edwards RR, Fillingim RB: Effects of age on temporal summation and habituation of thermal pain: Clinical relevance in healthy older and younger adults. J Pain. 2001; 2: 307-317.

Eisenberg E, Midbary A, Haddad M, et al.: Predicting the analgesic effect to oxycodone by ‘static’ and ‘dynamic’ quantitative sensory testing in healthy subjects. Pain. 2010; 151: 104-109.

Kleinböhl D, Hölzl R, Möltner A, et al.: Psychophysical measures of sensitization to tonic heat discriminate chronic pain patients. Pain. 1999; 81: 35-43.

Granot M, Sprecher E, Yarnitsky D: Psychophysics of phasic and tonic heat pain stimuli by quantitative sensory testing in healthy subjects. Eur J Pain. 2003; 7: 139-143.

Staud R, Robinson ME, Vierck CJ Jr, et al.: Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients. Pain. 2003; 101: 167-174.

Potvin S, Stip E, Tempier A, et al.: Pain perception in schizophrenia: No changes in diffuse noxious inhibitory controls (DNIC) but a lack of pain sensitization. J Psychiatr Res. 2008; 42: 1010-1016.

Eisenberg E, Burstein Y, Suzan E, et al.: Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain. Pain. 2015; 156: 381-385.

Maixner W, Fillingim R, Sigurdsson A, et al.: Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain: Evidence for altered temporal summation of pain. Pain. 1998; 76: 71-81.

Staud R, Vierck CJ, Cannon RL, et al.: Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome. Pain. 2001; 91: 165-175.

Price DD, Von der Gruen A, Miller J, et al.: psychophysical analysis of morphine analgesia. Pain. 1985; 22: 261-269.

Enggaard TP, Poulsen L, Arendt-Nielsen L, et al.: The analgesic effect of codeine as compared to imipramine in different human experimental pain models. Pain. 2001; 92: 277-282.

Eichenberger U, Giani C, Petersen-Felix S, et al.: Lumbar epidural fentanyl: Segmental spread and effect on temporal summation and muscle pain. Br J Anaesth. 2003; 90: 467-473.

Suzan E, Midbari A, Treister R, et al.: Oxycodone alters temporal summation but not conditioned pain modulation: Preclinical findings and possible relations to mechanisms of opioid analgesia. Pain. 2013; 154: 1413-1418.

Chen L, Malarick C, Seefeld L, et al.: Altered quantitative sensory testing outcome in subjects with opioid therapy. Pain. 2009; 143: 65-70.

Zhang Y, Ahmed S, Vo T, et al.: Increased pain sensitivity in chronic pain subjects on opioid therapy: A cross-sectional study using quantitative sensory testing. Pain Med. 2014; 16: 911-922.

You HJ, Dahl Morch C, Chen J, et al.: Simultaneous recordings of wind-up of paired spinal dorsal horn nociceptive neuron and nociceptive flexion reflex in rats. Brain Res. 2003; 960: 235-245.

Treede RD, Jensen TS, Campbell JN, et al.: Neuropathic pain: Redefinition and a grading system for clinical and research purposes. Neurology. 2008; 70: 1630-1635.

Potvin S, Paul-Savoie E, Morin M, et al.: Temporal summation of pain is not amplified in a large proportion of fibromyalgia patients. Pain Res Treat. 2012; 938595.

Tousignant-Laflamme Y, Pagé S, Goffaux P, et al.: An experimental model to measure excitatory and inhibitory pain mechanisms in humans. Brain Res. 2008; 230: 73-79.

Suzan E, Aviram J, Treister R, et al.: Individually-based measurement of temporal summation evoked by a noxious tonic heat paradigm. J Pain Res. 2015; 8: 409-415.

Minto CF, Schnider TW, Egan TD, et al.: Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997; 86: 10-23.

Minto CF, Schnider TW, Shafer SL: Pharmacokinetics and pharmacodynamics of remifentanil. II. Model application. Anesthesiology. 1997; 86: 24–33.

Eisenberg E, McNicol ED, Carr DB: Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: Systematic review and meta-analysis of randomized controlled trials. JAMA. 2005; 293: 3043-3052.

McNicol ED, Midbari A, Eisenberg E: Opioids for neuropathic pain. Cochrane Database Syst Rev. 2013; 8: CD006146.

Hina N, Fletcher D, Poindessous-Jazat F, et al.: Hyperalgesia induced by low-dose opioid treatment before orthopaedic surgery: An observational case-control study. Eur J Anaesthesiol. 2014; 32: 255-261.

Angst MS, Koppert W, Pahl I, et al.: Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003; 106: 49-57.

Hood DD, Curry R, Eisenach J: Intravenous remifentanil produces withdrawal hyperalgesia in volunteers with capsaicin-induced hyperalgesia. Anesth Analg. 2003; 97: 810-815.

Koppert W, Angst M, Alsheimer M, et al.: Naloxone provokes similar pain facilitation as observed after short-term infusion of remifentanil in humans. Pain. 2003; 106: 91-99.

Luginbühl M, Gerber A, Schnider TW, et al.: Modulation of remifentanil-induced analgesia, hyperalgesia, and tolerance by small-dose ketamine in humans. Anesth Analg. 2003; 96: 726- 727.

Guignard B, Bossard AE, Coste C, et al.: Acute opioid tolerance: Intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology. 2000; 93: 409-417.

Joly V, Richebe P, Guignard B, et al.: Remifentanil induced postoperative hyperalgesia and its prevention with small dose ketamine. Anesthesiology. 2005; 103: 147-155.

Song JW, Lee YW, Yoon KB, et al.: Magnesium sulfate prevents remifentanil-induced postoperative hyperalgesia in patients undergoing thyroidectomy. Anesth Analg. 2011; 113: 390-397.

Chu LF, D'Arcy N, Brady C, et al.: Analgesic tolerance without demonstrable opioid-induced hyperalgesia: A double-blinded, randomized, placebo-controlled trial of sustained-release morphine for treatment of chronic nonradicular low-back pain. Pain. 2012; 153: 1583-1592.

Published

07/01/2016

How to Cite

Suzan, PhD, E., A. Midbari, MD, D. Pud, PhD, S. Hadad, PhD, and E. Eisenberg, MD. “Clinical Analgesia Correlates With Decline in Temporal Summation in Response to Remifentanil Infusion in Patients With Chronic Neuropathic (radicular) Pain”. Journal of Opioid Management, vol. 12, no. 4, July 2016, pp. 251-8, doi:10.5055/jom.2016.0340.