Review article Piotr Jakubów1–4 , Urszula Kościuczuk1, 4, Juliusz Kosel1, 4, Piotr Soroko1, 5, Julia Kondracka1, 6, Mariola Tałałaj2 1Pain Management Unit “Vitamed”, Białystok, Poland 2Children and Adolescents Department od Anaesthesia and Intesive Care and Pain Therapy Unit, Białystok, Poland 3Department of Palliative Medicine, Medical University of Białystok 4Anaesthesia and Intensive Care Department, Medical University of Białystok, Bialystok, Poland 5Cardiology Department of the MSWiA (the Ministry of the Interior and Administration), Białystok, Poland 6Medical University of Gdańsk, Fourth-year Student of the Medical Faculty, Gdańsk, Poland The role of pregabalin in neuropathic pain management in cancer patients Abstract Despite the wide availability of analgesics for prescription in cancer pain, including both opioid and non-opi- oid medications, population studies have for many years demonstrated unadvisable pain management. International analyses indicate inadequate use of opioid and adjuvant drugs per capita. At the same time, patients complain about the accompanying pain, not treated effectively, especially in the course of cancer. One of the many causes of cancer pain that is difficult to treat is the co-occurrence of neuropathic pain. The article presents contemporary views on the treatment of neuropathic pain associated with cancer, including the site of application of gabapentinoids in the treatment scheme. Palliat Med Pract 2020; 14, 3: 175–182 Key words: cancer pain, neuropathic pain, pharmacotherapy, gabapentinoids, gabapentin, pregabalin Introduction is based on the anamnesis, physical examination and symptoms, particularly sensory disturbances [1, Despite the wide availability of analgesics for pain 8, 9]. The criteria allowing to determine a degree of management in cancer patients, including opioids and certainty for neuropathic pain diagnosis [10, 11] were non-opioid analgesics, the results of population stud- defined. The diagnostic criteria include the medical ies have shown ineffective pain treatment for many history of pain characteristics, neurological exam- years [1, 2]. Poland is a country with low consumption ination, neuroanatomical location and additional of opioid and adjuvant analgesics per capita [2–4]. At examinations [12, 13]. On the basis of the above-men- the same time, patients, especially cancer ones, point tioned criteria, the diagnosis of neuropathic pain to ineffective pain treatment [5, 6]. One of the reasons may be definite, probable or possible. In diagnostics for difficulties in pain treatment in cancer patients is and monitoring, the Neuropathic Pain Scales (NPSs) a neuropathic pain component [3, 7]. play an auxiliary role [14, 15]. In cancer patients, DN-4 (Douleur Neuropathique en 4 Questions) and Diagnosis and clinical evaluation NPQ (Neuropathic Pain Questionnaire) scales are most of neuropathic pain commonly used [13, 14]. Neuropathic pain has specific clinical presentation The diagnosis of neuropathic pain, both in cancer [1, 12, 15]. Patients describe pain as burning, pierc- patients and in the course of other chronic diseases, ing, tearing, blunt, stitching, crushing or tingling [6, Address for correspondence: Piotr Jakubów “Vitamed” Pain Management Unit ul. Konopnickiej 34, 15–586 Białystok, Poland e-mail: [email protected] Palliative Medicine in Practice 2020; 14, 3, 175–182 Copyright © Via Medica, ISSN 2545–0425 DOI: 10.5603/PMPI.2020.0020 www.journals.viamedica.pl/palliative_medicine_in_practice 175 Palliative Medicine in Practice 2020, tom 14, nr 3 7, 13]. The pain occurs idiopathically or under the The definition of neuropathic pain developed by influence of physical and emotional stimuli. It can be NeuPSIG indicates that it is the pain which is a direct very intense as well as recurrent or permanent. In consequence of a lesion or disease affecting the cancer patients, neuropathic pain, compared to other somatosensory nervous system, provoked by various types of pain, is characterised by worse response to causes, especially in cancer patients (Table 1) [16, 24, analgesics [16, 17]; however, it is not always the case 27]. On this basis, neuropathic pain classification sys- with anticonvulsants and antidepressants [18, 19]. tem (definite, probable and possible) was introduced. In the course of neuropathic pain, such conditions The distinction between neuropathic pain caused by as allodynia (hyperaesthesia due to a stimulus which cancer and other causes of that type of pain has not normally does not cause pain) and hyperalgesia (exces- been made in the existing ICD classifications. Common sive pain sensation, disproportionate to the strength for cancer-related as well as non-cancer-related pain, of the stimulus) and hypoalgesia, i.e. reduced pain there was a symptomatic diagnosis of R52, which sensation, are frequently observed [10, 13, 20, 21]. describes pain that is not classified elsewhere. The Apart from sensory disturbances, neuropathic pain ICD-10 classification, introduced in 2019 in the Unit- is also characterised by cognitive dysfunctions (atten- ed States, for the first time included the diagnosis of tion deficit disorders, short-term memory impairment) pain as a unit of neoplastic disease [28]. In the new which cause mental lability and ‘wait for pain’ position ICD-10 CM classification (2020 version), published in [10, 20]. Due to the persistent nature of neuropathic 2019 by the American Medical Society, the G89.3 code pain, which is often resistant to treatment, there is concerning the occurrence of neoplasm-related pain a fear of recurrence and intensification of pain, which was included. This record concerns both acute and hinders daily functioning and deteriorates the quality chronic pain, including cancer-associated pain, pain of life. Pain is accompanied by sleep problems, nervous- due to malignancy (primary, secondary), tumor-asso- ness, chronic fatigue, lack of will and desire to treat the ciated pain and pain due to neoplastic disease. In the underlying disease [18]. Untreated neuropathic pain new version of the ICD-11 classification developed by is characterised by insomnia, anxiety and depression WHO for various cultural parts of the world, including caused by the accumulation of inflammatory cytokines Europe, proposed to apply from 2021, an accurate due to stress, ejection of catecholamines, activation international classification of chronic pain, including of the hypothalamo-pituitary axis and disturbances neuropathic pain and neoplasm-related pain was of central transmission, causing depression [20–22]. included as well [29, 30]. Pending the publication of Analgesics are then used together with anxiolytic new European diagnosis codes for neuropathic pain, drugs and antidepressants. When neuropathic pain the symptomatic diagnosis of code R52 pain remains treatment in cancer patients is abandoned, due to the valid. The causes of neuropathic pain in cancer pa- mental changes the patients tend to neglect anticancer tients are presented in Table 1. and symptomatic treatment. The diagnosis of neuro- pathic pain in cancer patients does not differ from the Pharmacotherapy of neuropathic pain diagnosis of neuropathy caused by other causes and it is based on detailed data from anamnesis, physical In 2005, IASP developed recommendations for the examination and diagnostic tests [23]. pharmacological treatment of neuropathic pain based According to NeuPSIG [Neuropathic Pain Special on Evidence-Based Medicine (EBM) principles. In 2006, Interest Group — International Association for the the recommendations of the European Federation Study of Neuropathic Pain (IASP)], repetitive diagnostic of Neurological Societies were published, which, in schemes are recommended for the diagnosis of neu- addition to the data concerning efficacy of medicines, ropathic pain [24]. Determination of the probability of include data on quality of life, the effect of treatment neuropathic pain occurrence comprises data from the on sleep and the consequence of comorbidities. In patient’s clinical interview, the assessment of sensory subsequent years, numerous recommendations for descriptors suggesting the neuropathic mechanism treatment of neuropathic pain were published [1, of pain — e.g. triggering, twingeing, numbness and 14, 15, 31]. In 2007, recommendations for the neu- tingling — and location of those symptoms in the neu- ropathic pain management in patients with chronic roanatomic system [24, 25]. The clinical examination non-cancer-related pain were developed, which (with of sensory changes includes the assessment of touch subsequent updates) include: sensation, the sense of vibration, prickling sensation, I. Symptomatic treatment should be preceded by temperature sensitivity, using a swab, ampoule with a diagnosis of the cause of neuropathic pain cold and warm fluid or tuning fork in order to de- and, if possible, followed by appropriate causal termine the extent of nervous system damage [26]. treatment. 176 www.journals.viamedica.pl/palliative_medicine_in_practice Piotr Jakubów et al., The role of pregabalin in neuropathic pain management in cancer patients Table 1. Neuropathic pain syndromes in cancer patients Directly — Tumor-related or metastasis-related compression or infiltration of the skull or CNS structures, cer- cancer-related vical nerves in the course of cervical, jaw, palate, salivary gland cancers, metastatic lung, breast, neuropathic kidney, testicular, ovarian, prostate, melanoma cancers; childhood cancers: embryonic neuroma, pain striated myosarcoma,