According to the updated definition of the International Association for the Study of Pain (IASP), NB is a condition caused by damage or disease of the somatosensory system. Updated detection was made with the aim to differentiate NB from pain or nociceptive cent – eral origin. In addition, the updated definition indicates the need for a survey to establish the relationship between pain and damage / disease of the somatosensory system (Finnerup N. et al., 2016).
Various types of NB can occur in postherpetic neuralgia, diabetic neuropathy, spinal cord injury, multiple sclerosis, and stroke (Fig. 1). In the international guidelines on the treatment of the National Bank recommended the use of step-wise approach for the collection of evidence in favor of a possible, probable or set NB (Haanpaa M. et al, 2010;. Finnerup . N. The et al, 2017) (Fig. 2). Pain markers such as tingling and burning may indicate a neuropathic origin of pain (Haanpaa M. et al., 2011; Colloca L. et al., 2017). In some patients it may pain syndrome of mixed genesis is noted. However, the assumption that any pain has a neuropathic component is erroneous (Magrinelli F. et al., 2013).
Preparations for the treatment of NB may be assigned not in accordance with readings (Wettermark B. et al, 2014;. Goodman C. et al, 2017.). Therefore, understanding the mechanism of pain development and the underlying pathological conditions is important for choosing the optimal treatment strategy.
Effective NB therapy remains a challenge for healthcare professionals. Partial pain relief is currently seen as a good treatment outcome. Prescribing medications is part of the overall pain management strategy aimed at improving the quality of life and working capacity.
What drugs should be used to treat NB? There is limited evidence in favor of choosing non-steroidal anti-inflammatory drugs (Wiffen P. et al. 2016; Moore R. et al. 2015). The possibility of using opioid analgesics in patients with NB is also significantly limited due to potential side effects and weak evidence base. relatively long term efficiency (Finnerup N. B. et al., 2015). In accordance with the European guidelines (NICE2015) at NB in – first-line treatment include drugs such as pregabalin, amitriptyline, duloxetine and gabapentin. The representative of the new generation of gabapentinoids, pregabalin, deserves special attention. The main field of application of this antiepileptic drug covers conditions accompanied by NB, which is more targeted by pregabalin compared to gabapentin. In clinical studies, pregabalin demonstrated effective reduction of the National Bank together with the positive impact on – the quality of life and – neurological symptoms of patients. On the pharmaceutical market of Ukraine, pregabalin is represented by the drug Linbag (Sandoz company).
Efficacy of pregabalin in NB of various etiologies
Clinical studies of the efficacy of pregabalin in patients with NB have been actively carried out over the past decades, which has contributed to the accumulation of an extensive evidence base. As a treatment for painful diabetic peripheral neuropathy and postherpetic neuralgia, pregabalin has been studied in a number of randomized double-blind studies and 3 meta-analyzes (Freeman et al., 2008; Hurley et al., 2008; Quilici et al., 2009). In four randomized, placebo-controlled trials assessing the efficacy of pregabalin in fixed doses (150, 300 and 600 mg / day) of the patients with postherpetic neuralgia (Dworkin et al, 2003;.. Sabatowski et al, 2004; Stacey et al, 2008.; van Seventer et al., 2006). A dose-dependent response rate to therapy was shown : 26% while taking a dose of 150 mg / day, 26-39% – 300 mg / day, and 47-50% – 600 mg / day. These results were subsequently confirmed by a meta-analysis by Moore et al. (2009).
According to a randomized clinical trial by Jenkins et al. (2012), pregabalin effectively relieved post-traumatic peripheral pain. The pregabalin group showed a significantly greater reduction in pain scores compared with placebo. The patients treated with pregabalin also had higher levels of morning physical activity.
In a number of clinical studies have been conducted to compare the efficacy of pregabalin and other first-line drugs, as well as opioid analgesics. So, the purpose of the study E. Raptis et al. (2014) studied the effect of pregabalin in tumor-associated NB and compared its effects with those of opioid analgesics. The results of the study showed that pregabalin can improve pain control and reduce the need for patients to use opioids. Of the total number of patients, 55% reached the primary endpoint (decrease visual analogue scale (VAS) by 30% compared to baseline), with 73.33% (44) participants in the pregabalin group, while only 36.67% (22) patients in the opioid analgesic group (Fig. . 3). In addition, early pregabalin administration reduced the risk of adverse events associated with high-dose opioid analgesics . Thus, adverse reactions were reported in 26.7% of patients in the pregabalin group and in 56.7% in the fentanyl group (p = 0.009). Results presented Studies indicate that the neuropathic component of pain in cancer patients responds more effectively to pregabalin therapy than potent opioid analgesics.
A. Gunseli et al. (2017) conducted a comparative study of the efficacy of pregabalin and s – triptilina in patients with fibromyalgia. The results of the study showed a more pronounced effect of amitriptyline in reducing experimentally measured pain. However , pregabalin was found to be more effective in reducing patients’ neuropathic complaints. In this regard, the authors believe that it is pregabalin that should be recommended for administration to persons with fibromyalgia.
In 2018, a comparative study of the efficacy of pregabalin and duloxetine in patients with taxane-induced neuropathy was conducted (Razieh A. et al., 2018). Using both drugs was accompanied by comparable positive effects on the overall health and quality of life of study participants. The authors of this work noted that the advantage of using pregabalin was a more pronounced reduction in pain (Fig. 4) and manifestations of insomnia.
Safety and drug interactions
In almost all studies, including post-marketing, pregabalin was well tolerated. Most side effects were mild to moderate and were usually transient. G. Irving et al. (2014) studied the safety of pregabalin in comparison with that of another drug of the first line of treatment for NB – duloxetine. The authors of the study found a significantly higher rate of side effects (19.6%) in the duloxetine group compared with pregabalin (10.4%).
Interactions between gabapentinoids and other drugs are very rare, due to the absence of a significant connection with plasma proteins and an inducing or inhibitory effect on the main isozymes of cytochrome P450 in vitro. The pharmacokinetics of the drug is not dependent on – the genetic polymorphism isozymes P450 (Blockbrader et al, 2010.). There is also no clinically significant effect on the pharmacokinetics / pharmacodynamics of pregabalin from other drugs (Cada et al., 2006). These advantages of pregabalin are especially important when we consider the need for its use in patients with comorbid conditions who are receiving drug therapy for the underlying disease.
The key factor in the successful therapy of NB is the choice of the optimal drug that has a positive effect on the patient’s quality of life, promotes effective pain reduction and has a high safety profile. According to international recommendations, pregabalin is included in the first line therapy of NB. Pregabalin has proven effective in numerous clinical studies. The high safety profile and minimal likelihood of drug interactions make pregabalin the optimal choice for patients with comorbid conditions. On the pharmaceutical market of Ukraine, pregabalin is represented by the drug Linbag ( Sandoz company ).