Tapentadol in the management of chronic low back pain: a novel approach to a complex condition?

Abstract

Chronic pain affects approximately 1 in 5 people in Europe, and around half of sufferers receive inadequate pain management. The most common location is the lower back. Pharmacological treatment of this condition is challenging because of the range of causative mechanisms and the difficulty of balancing analgesic efficacy and tolerability. An international panel of clinical pain specialists met in September, 2009, to discuss the treatment of chronic low back pain, and to review preclinical and clinical data relating to the new analgesic, tapentadol. A lack of consensus exists on the best treatment for low back pain. The range of regularly prescribed pharmacological agents extends from nonopioids (paracetamol, NSAIDs, and COX-2 inhibitors) to opioids, antidepressants and anticonvulsants. Pain relief may be compromised, however, by an undetected neuropathic component or intolerable side effects. Treatment is potentially life-long and effective analgesics are urgently needed, with demonstrable long-term safety. Combining separate agents with different mechanisms of action could overcome the limitations of present pharmacological therapy, but clinical evidence for this approach is currently lacking. Tapentadol combines μ-opioid agonism with noradrenaline reuptake inhibition in a single molecule. There is strong evidence of synergistic antinociception between these two mechanisms of action. In preclinical and clinical testing, tapentadol has shown efficacy against both nociceptive and neuropathic pain. Preclinical data indicate that tapentadol's μ-opioid agonism makes a greater contribution to analgesia in acute pain, while noradrenaline reuptake inhibition makes a greater contribution in chronic neuropathic pain models. Tapentadol also produces fewer adverse events than oxycodone at equianalgesic doses, and thus may have a 'μ-sparing effect'. Current evidence indicates that tapentadol's efficacy/tolerability ratio may be better than those of classical opioids. However, further research is needed to establish its role in pain management.

Keywords: chronic low back pain; efficacy/side effect ratio; multimechanistic approach; neuropathic component; neurophysiological changes; tapentadol.

Figures

Figure 1

Differential contribution of μ-opioid agonism and noradrenaline reuptake inhibition in acute and chronic neuropathic pain models. In acute pain, antagonizing μ-opioid agonism with naloxone moves the dose–response curve further to the right than antagonizing noradrenaline reuptake inhibition with yohimbine, showing that μ-opioid agonism makes a greater contribution to the compound’s analgesic effect. In chronic neuropathic pain, the opposite is true; noradrenaline reuptake inhibition contributes more to analgesia. Reprinted from European Journal of Pain, vol 14, issue 8. Schröder W, De Vry J, Tzschentke TM, Jahnel U, Christoph T. Differential contribution of opioid and noradrenergic mechanisms to the antinociceptive and antihypersensitive efficacy of tapentadol in rat models of nociceptive and neuropathic pain, 814–821, Copyright (2010), with permission from Elsevier. Abbreviation: MPE, maximum possible effect.

Figure 2

Average pain intensity scores over time. Pain relief was consistent during the maintenance period for both active treatment groups. Tapentadol PR significantly reduced mean pain intensity compared with placebo at week 12 and throughout the maintenance period, using the last observation carried forward imputation method for missing values. Used with permission of Informa Healthcare, from Expert Opinion on Pharmacotherapy, Buynak R, et al, Vol 11, Issue 11, 2010; permission conveyed through Copyright Clearance Center, Inc. Abbreviations: CR, controlled release; PR, prolonged release.

Figure 3

Treatment discontinuations over time. The time to discontinuation in the tapentadol PR group was significantly longer than in the oxycodone CR group (P < 0.001), but not significantly different from that in the placebo group (P = 0.309). The primary reason for treatment discontinuation in the active treatment groups was adverse events (16.7% of the tapentadol PR group, compared with 32.3% of the oxycodone CR group). Used with permission of Informa Healthcare, from Expert Opinion on Pharmacotherapy, Buynak R, et al, Vol 11, Issue 11, 2010; permission conveyed through Copyright Clearance Center, Inc. Abbreviations: CR, controlled release; PR, prolonged release.

Figure 4

Weekly average pain intensity scores. During the double-blind maintenance period, the mean pain intensity increased in the placebo group but remained stable in the tapentadol PR group. Tapentadol PR also showed a favorable tolerability profile, with a maximum of about 20% for individual adverse events. Used with permission of Informa Healthcare, from Current Medical Research and Opinion, Schwartz S, et al, Vol 27, Issue 1, 2011; permission conveyed through Copyright Clearance Center, Inc. Abbreviations: OL, open label; DB, double blind; PR, prolonged release.

Figure 5

Discontinuations and mean pain intensity scores over time in patients suffering from low back pain and osteoarthritis., A) The percentage of patients who discontinued treatment because of adverse events was lower for tapentadol than for oxycodone (22.7% vs 36.8%). The overall percentage of patients who discontinued treatment was also lower for tapentadol than for oxycodone (53.8% vs 65%). B) Tapentadol PR provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year. The efficacy of tapentadol PR was comparable to that of oxycodone CR. Figure 5B from Pain Practice, Vol 10, Wild et al. Copyright © 2010 by John Wiley & Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc; permission conveyed through Copyright Clearance Center, Inc. Abbreviations: CR, controlled release; PR, prolonged release; TEAEs, treatment-emergent adverse events.