Current Considerations for the Treatment of Severe Chronic Pain: The Potential for Tapentadol

Abstract

Studies suggest that around 20% of adults in Europe experience chronic pain, which not only has a considerable impact on their quality of life but also imposes a substantial economic burden on society. More than one-third of these people feel that their pain is inadequately managed. A range of analgesic drugs is currently available, but recent guidelines recommend that NSAIDs and COX-2 inhibitors should be prescribed cautiously. Although the short-term efficacy of opioids is good, adverse events are common and doses are frequently limited by tolerability problems. There is a perceived need for improved pharmacological treatment options. Currently, many treatment decisions are based solely on pain intensity. However, chronic pain is multifactorial and this apaproach ignores the fact that different causative mechanisms may be involved. The presence of more than one causative mechanism means that chronic pain can seldom be controlled by a single agent. Therefore, combining drugs with different analgesic actions increases the probability of interrupting the pain signal, but is often associated with an increased risk of drug/drug interactions, low compliance and increased side effects. Tapentadol combines μ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule, with both mechanisms contributing to its analgesic effects. Preclinical testing has shown that μ-opioid agonism is primarily responsible for analgesia in acute pain, whereas noradrenaline reuptake inhibition is more important in chronic pain. In clinical trials in patients with chronic pain, the efficacy of tapentadol was similar to that of oxycodone, but it produced significantly fewer gastrointestinal side-effects and treatment discontinuations. Pain relief remained stable throughout a 1-year safety study. Thus, tapentadol could possibly overcome some of the limitations of currently available analgesics for the treatment of chronic pain.

Spinal neuronal correlates of tapentadol analgesia in cancer pain: A back‐translational approach

“…Preclinical data reveals an independence of these complimentary modes of action yet a synergy between these two mechanisms (Schroder et al, 2011). Tapentadol is effective in patients with acute and chronic pain states, such as post-operative pain, osteoarthritis, peripheral neuropathy and lower back pain, and has similar analgesic effects to oxycodone and morphine, but with significantly fewer side effects and discontinuations (Hale et al, 2009;Wade and Spruill, 2009;Lange et al, 2010;Riemsma et al, 2011;Pergolizzi et al, 2012). In cancer patients, controlled studies of tapentadol are still lacking.…”

The Noradrenergic Component in Tapentadol Action Counteractsμ-Opioid Receptor–Mediated Adverse Effects on Adult Neurogenesis

“…Both preclinical and clinical studies show that tapentadol is a novel centrally acting analgesic drug that has efficacy comparable with that of strong opiates in a broad spectrum of acute and chronic pain conditions, with an improved tolerability profile compared with classic opiates (Tzschentke et al, 2007(Tzschentke et al, , 2009Kress, 2010;Sloan, 2010;Etropolski et al, 2011;Riemsma et al, 2011;Hartrick and Rodríguez Hernandez, 2012;Pergolizzi et al, 2012). Tapentadol combines MOR agonistic activity with norepinephrine reuptake inhibition (NRI) in a single molecule (Tzschentke et al, 2007;Bee et al, 2011;Hartrick and Rozek, 2011;Schröder et al, 2011).…”

Tapentadol: what every doctor needs to know about this new drug

“…Its central analgesic action occurs by means of two mechanisms: 1) as an agonist of the μ-opioid receptors (MOR), with the same affinity or 10 times higher on KOR receptors (k-opioid receptor) REVIEW ARTICLE DOI 10.5935/2595-0118.20180015 and DOR (delta opioid receptor) 4 ; 2) as a norepinephrine reuptake inhibitor (NRI). The MOR affinity is considered modest when compared to pure agonists, such as morphine 9,10 , whose affinity is 44 to 50 times higher 2,4 . Its NRI action increases the norepinephrine release by the pain descending inhibitory pathways in the dorsal horn of the spinal cord, allowing the substance to accumulate in the synapses.…”

“…The relevance of the dual mechanism of action was investigated by combining tapentadol with naloxone or alpha 2 yohimbine in models of acute and chronic pain. It was noted that the opi- oid agonist contributes to analgesia in acute pain, whereas the NRI action played a fundamental role in chronic pain 2 . Another important factor related to the NRI action is its usefulness in chronic neuropathic pain 20 .…”

“…Despite the extraordinary advances in anatomy, physiology, diagnosis and pain management, more than 50% of patients report improper relief. This can be related to the neuroplasticity process of the pain pathways 1 , creating a persistent "memory" of the aggressive event and neuronal hiperexcitability 2,3 . Understanding chronic pain neurobiology is fundamental to target the treatment.…”