Tapentadol Provided Pain Relief and Improved Sleep in Patients with Chronic Musculoskeletal Pain

PainRelief.com Interview with:
Dr Renato Vellucci
Contract Professor University of Florence
Pain and Palliative care Clinic
University Hospital of Careggi
Florence, Italy

Dr. Vellucci

PainRelief.com:  What is the background for this study?  What are the main findings?

Response: Chronic low back pain (CLBP) is the most prevalent chronic pain (CP) condition and the leading global cause of years lived with disability. According to the axiom pain as a biopsychosocial issue, mood and sleep disturbances represent key issues. However, the impact of different analgesic therapies on quality of life (QoL) and functional recovery has been poorly assessed to date. Focusing on combination of chronic pain and sleep, they both perform a mutual reinforcement.

Pain disorganizes the sleep architecture, and disturbed and unrefreshed sleep increases spontaneous pain and lowers pain thresholds. Sleep disorders may augment stress levels, thus making it difficult for patients to perform simple tasks impairing their cognitive ability. Poor sleep may predict the growth and intensification of pain over time, with increased insomnia symptoms being both a predictor and an indicator of worse pain outcomes and physical functioning status over time. Epidemiology of chronic pain unequivocally demonstrates the role of sleep quality in the development of chronic pain.

Notwithstanding this strong two-way relationship between chronic pain and sleep, little knowledge is available about the neurochemical determinants of this interplay and therapeutical strategies to break this vicious circle. Fifty percent of people with chronic low back pain have sleeping disturbances, with an 18-fold increase in insomnia versus healthy people. A recent study investigated the relationship between sleep disturbances and back pain and found that it is two sided with sleep disturbance being associated with risk of back pain whilst back pain can also lead to sleep disturbances. Thus, it can be hypothesized that, by reducing pain and physical dysfunction, sleep quality could be improved, thus enriching the QoL of people with CLBP.

Similarly, improvements in sleep after cognitive behavioral therapy in patients with chronic pain due to osteoarthritis were associated with reduced pain. Earlier evidence suggested that tapentadol prolonged-release treatment ameliorate in parallel QoL and sleep quality in a greater proportion of patients compared to that of patients following oxycodone/naloxone prolonged- release treatment (50% versus 37.7%). Other tapentadol studies conducted in a real-life context documented, along with effective pain control, similar improvements in mental and physical health and suggested beneficial effects in terms of less night awakenings and greater percentages of patients reporting restful sleep.

PainRelief.com:  What is tapentadol?

Response: Tapentadol is the archetype of the new class of compounds named MOR-NRI, provides meaningful analgesic benefits interacting with the ascending pathways responsible for pain perception and descending tracts that suppress noxious transmission. Tapentadol displays two synergistic mechanisms of action: MOR agonism and noradrenaline reuptake inhibition. MOR action inhibits the ascending pain signals and the inflow of intracellular calcium ions at the spinal cord level and, in the PAG, inhibit the release of gamma-aminobutyric acid (GABA) that promotes an augmented noradrenaline release, while the NRI component provides a powerful inhibitory action on spinal overactivity via the alpha-2-adrenergic receptors in the spinal cord and brain. These properties are of outmost relevance to tapentadol clinical efficacy in patients with nociceptive, neuropathic and mixed pain. Due to its unique combination of MOR and NRI activity, tapentadol holds promise to simplify chronic pain treatment by eliminating the need to isolate and treat the individual types of CP with a combination of different analgesics.

PainRelief.com:  What are the main findings?

Response: We pooled data from eight real-world studies including 487 patients with chronic pain (mean age, 68.3 years; 57.7% women) who received treatment with tapentadol for different painful conditions, including LBP, neck pain and pain after knee replacement. All studies were open-label, four were prospective and two were retrospective studies. The new definition of CP as a single disease entity acknowledges both the multidimensional nature of pain and the evolving notion of pain as a biopsychosocial issue and adds further emphasis to QoL and functional recovery.

Improvement of such outcomes, which are highly valued by patients should be regarded as the main goal of an analgesic therapy. By virtue of the two-sided relationship between pain intensity and sleep, and the neurobiological link between pain control and the associated subjective improvement in sleep, we speculate that a reduction in pain intensity provided by tapentadol can improve sleep quality as well as favouring a better QoL. Therefore, pain reduction would be a necessary condition for sleep to improve. We clearly recognize the limits of this statistical analysis, considering that patient population, painful conditions and even treatment duration were different in each study and therefore not directly comparable. Notwithstanding this, our findings suggest that tapentadol provided significant pain control compared with baseline conditions, which was paralleled by subjective improvements in sleep quality in terms of a reduction in night awakenings and greater percentages of patients reporting restful sleep.

The findings of our pooled analysis showed a five-fold reduction in the frequency of very disturbed sleep. Furthermore, tapentadol treatment precipitate a two-fold reduction in the predominant sleep complaint reported by chronic pain patients – that is, nocturnal awakenings. Additionally, a significantly greater proportion of patients reporting good/ restful sleep at the end of the study period compared to baseline was also found (72.4% versus 25.3%; p<0.01). Of great value, this benefit was observed regardless of the clinical setting, treatment duration, posology or patient age and was associated with a higher proportion of patients reporting an improved global health status and good tolerability. Opioid therapy is known to affect sleep in different ways. Individuals on opioids report an increase in daytime somnolence, which may be related to higher doses of opioids but also give a subjective description of improved sleep quality. Thus, it is crucial to effectively discriminate the observed benefit on sleep quality from the somnolence that opioids may induce in chronic pain patients. In this regard, a recent review examining the effects of opioid therapy on sleep in CP showed that, when an improvement in sleep could be observed, this was accompanied by daytime sleepiness and other undesirable side effects with “somnolence”, “sedation”, “drowsiness” and “sleepiness” being the most frequently reported sleep-related adverse event.

Our analysis suggested that, the significant pain relief is associated with improved sleep quality, and no serious or severe adverse events occurred and drowsiness was reported as occurring in only one study after two weeks of treatment but disappearing by the end of the treatment period. Of note, when assessing the outcome “somnolence”, there was evidence in favour of tapentadol when compared with oxycodone and oxymorphone.  

PainRelief.com: What should readers take away from your report?

Response: The concept of functionality stands as an additional outcome that clinicians should keep in mind when selecting pain medications for patients with chronic pain as it encompasses relevant domains of patients’ QoL, including sleep quality. Tapentadol, the archetype of the new class of compounds named MOR-NRI, offered significant pain control compared with baseline conditions, which was paralleled by subjective improvements in sleep quality in terms of a reduction in night awakenings and greater percentages of patients reporting restful sleep. Opioid therapy was accompanied, when an improvement in sleep could be observed, by daytime sleepiness and other undesirable side effects. Our analysis suggested that, tapentadol offer a significant pain relief associated with improved sleep quality, and no serious or severe adverse events occurred. Of note, tapentadol was superior to oxycodone and oxymorphone, when assessing the outcome “somnolence”. 

PainRelief.com: What recommendations do you have for future research as a result of this work?

Response: Our findings provide the rationale for addressing sleep quality as a relevant outcome, complementary to pain relief in chronic pain management, and prompt us to further investigate the intimate link connecting pain control and sleep quality by designing studies involving polysomnography and measurements of total sleep time and sleep efficiency.

No disclosures


Pain reduction induced by tapentadol in patients with musculoskeletal chronic pain fosters better sleep quality.

Vellucci R, De Rosa G, Piraccini E.Drugs Context. 2021 Apr 19;10:2020-12-9. doi: 10.7573/dic.2020-12-9. eCollection 2021.

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