NADA Ear Acupuncture and Medical Acupuncture for Pain- and Health-Related Quality of Life among Older Patients with Chronic Nonspecific Low Back Pain: A Prospective Clinical Trial.

BACKGROUND: The purpose of this study was to investigate the efficacy and safety of the NADA (National Acupuncture Detoxification Association)-standardized ear acupuncture protocol in comparison to medical acupuncture (MA) in the treatment of chronic nonspecific low back pain (LBP) in older adults. METHODS: This was a prospective, clinical, single center, open label, comparative study. A total of 60 older patients with chronic nonspecific LBP were enrolled in the study. The patients were divided into two groups. The MA group received treatment with medical acupuncture (MA), while the NADA group received NADA ear acupuncture once a day for 20 min, for a total of 10 sessions. The co-primary outcome measures were the reduction in pain intensity evaluated by the Numeric Rating Scale (NRS) compared to baseline and improvement in patients' quality of life (QOL) assessed in the SF-36 questionnaire before and after treatment; this was compared between the two groups. RESULTS: After two weeks of treatment, a significant reduction compared to baseline was observed in the NRS scores following treatment with medical acupuncture as well as after the utilization of NADA ear acupuncture protocol: NRS score for average pain experienced by the patients over the previous week (NRSa) MA: p = 0.002; NADA: p < 0.001, maximum NRS score in the past week (NRSm) MA: p < 0.001; NADA: p < 0.001, and NRS score at the time of examination (NRSe) MA: p = 0.001; NADA: p < 0.001. Reduction of the NRSa score compared to baseline was significantly greater in the NADA group (p = 0.034). Significant improvements in the QOL of patients according to the SF-36 questionnaire compared to baseline were observed in the MA group in the following domains: PF (p = 0.003), RP (p = 0.002), SF (p = 0.041), RE (p = 0.005), MH (p = 0.043), HT (p = 0.013), PCS (p = 0.004), and MCS (p = 0.025); and in the NADA group, in the following domains: PF (p = 0.004), RP (p = 0.048), BP (p = 0.001), VT (p = 0.035), RE (p = 0.006), MH (p < 0.001), HT (p = 0.003), PCS (p < 0.001), and MCS (p < 0.001). There were minor complications observed in 35% of patients (total of 20 participants); 31% (9 patients) in the MA group and 39% (11 patients) in the NADA group. These were minor and quickly resolved, including insertion point pain, minor bleeding after needle removal, and one instance of fainting. No patients in either group reported worsening of LBP. These complications occurred in 4.14% of MA sessions (12 times/290 sessions) and in 6.07% of NADA acupuncture sessions (16 times/280 sessions). CONCLUSION: The outcomes of this study suggest that both MA and NADA ear acupuncture could be a valuable and personalized component of a comprehensive approach to managing chronic nonspecific LBP in older patients. Incorporation of MA and NADA ear acupuncture into the clinical management of chronic nonspecific LBP in elderly patients has the potential to reduce pain intensity and improve the overall quality of life of affected individuals. However, further studies are needed to confirm our findings.

Promoting whole person health: Exploring the role of traditional Chinese medicine in Polish healthcare.

Poland has a unique history of traditional Chinese medicine (TCM) dating back to the 17th century when Polish missionary Michael (Michal) Boym was a pioneer in the field. In the 20th century, his successor, Professor Zbigniew Garnuszewski, reintroduced acupuncture to medical practice in Poland. However, other methods of TCM and its holistic approach to patient care have not found their place in modern medicine in Poland. At present, the legal status of TCM in Poland remains unregulated, with TCM included in the broad spectrum of complementary and alternative medicine (CAM) practices. Few reports are available on the use of TCM methods among the Polish population. Integrative medicine combines conventional medicine with evidence-based CAM interventions and considers all aspects of a patient's health, including physical, emotional, mental, social, and environmental factors. An integrative healthcare model that incorporates TCM modalities and lifestyle recommendations as well as a whole person approach may provide a more sustainable solution for the constantly underfinanced Polish healthcare system, which faces challenges of multimorbidity in an aging society and limited access to care. The coronavirus disease 2019 pandemic, war in Ukraine, and ongoing climate crisis have underscored the need to strengthen the resilience of the Polish healthcare system and search for new solutions. A model of care that blends the best of biomedicine and TCM healing approaches may be a better option for both patients and the healthcare system in Poland. Please cite this article as: Rybicka M, Zhao J, Piotrowicz K, Ptasnik S, Mitka K, Kocot-Kepska M, Hui KK. Promoting whole person health: Exploring the role of traditional Chinese medicine in Polish healthcare. J Integr Med. 2023; 21(6): 509-517.

Mirogabalin Decreases Pain-like Behaviors by Inhibiting the Microglial/Macrophage Activation, p38MAPK Signaling, and Pronociceptive CCL2 and CCL5 Release in a Mouse Model of Neuropathic Pain.

Neuropathic pain is a chronic condition that significantly reduces the quality of life of many patients as a result of ineffective pain relief therapy. For that reason, looking for new analgesics remains an important issue. Mirogabalin is a new gabapentinoid that is a specific ligand for the α2σ-1 and α2σ-2 subunits of voltage-gated calcium channels. In the present study, we compared the analgesic effect of pregabalin and mirogabalin in a neuropathic pain chronic constriction injury (CCI) of the sciatic nerve in a mouse model. The main purpose of our study was to determine the effectiveness of mirogabalin administered both once and repeatedly and to explain how the drug influences highly activated cells at the spinal cord level in neuropathy. We also sought to understand whether mirogabalin modulates the selected intracellular pathways (p38MAPK, ERK, JNK) and chemokines (CCL2, CCL5) important for nociceptive transmission, which is crucial information from a clinical perspective. First, our study provides evidence that a single mirogabalin administration diminishes tactile hypersensitivity more effectively than pregabalin. Second, research shows that several indirect mechanisms may be responsible for the beneficial analgesic effect of mirogabalin. This study reports that repeated intraperitoneally (i.p.) mirogabalin administration strongly prevents spinal microglia/macrophage activation evoked by nerve injury, slightly suppresses astroglia and neutrophil infiltration, and reduces the p38MAPK levels associated with neuropathic pain, as measured on Day 7. Moreover, mirogabalin strongly diminished the levels of the pronociceptive chemokines CCL2 and CCL5. Our results indicate that mirogabalin may represent a new strategy for the effective pharmacotherapy of neuropathic pain.

Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain.

Neuropathic pain remains a clinical challenge due to its complex and not yet fully understood pathomechanism, which result in limited analgesic effectiveness of the management offered, particularly for patients with acute, refractory neuropathic pain states. In addition to the introduction of several modern therapeutic approaches, such as neuromodulation or novel anti-neuropathic drugs, significant efforts have been made in the repurposing of well-known substances such as phenytoin. Although its main mechanism of action occurs at sodium channels in excitable and non-excitable cells and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level and how it influences morphine-induced analgesia have not been clarified, both being crucial from a clinical perspective. We demonstrated that single and repeated systemic administrations of phenytoin decreased tactile and thermal hypersensitivity in an animal model of neuropathic pain. Importantly, we observed an increase in the antinociceptive effect on thermal stimuli with repeated administrations of phenytoin. This is the first study to report that phenytoin improves morphine-induced antinociceptive effects and influences microglia/macrophage activity at the spinal cord and dorsal root ganglion levels in a neuropathic pain model. Our findings support the hypothesis that phenytoin may represent an effective strategy for neuropathic pain management in clinical practice, particularly when combination with opioids is needed.

Conventionally fractionated radiotherapy versus CyberKnife hypofractionated radiotherapy for painful vertebral haemangiomas - A randomized clinical trial.

BACKGROUND AND PURPOSE: The outcomes of conventional radiotherapy for painful vertebral haemangiomas have been improved through dose escalation at the expense of overall treatment time. We hypothesized that with the aid of precise hypofractionated radiotherapy, it is possible to safely deliver a similar biological equivalent dose over a significantly shorter course of treatment with a comparable efficacy and safety. MATERIALS AND METHODS: In this prospective, single-institution unblinded randomized clinical trial (NCT02332408) patients with painful vertebral haemangiomas were allocated one-to-one either to 25 Gy delivered in five fractions (CK) or conventionally fractionated radiotherapy up to 36 Gy (conv.). The main endpoint was pain relief at two years, measured on a subjective and numerical scale (NRS). RESULTS: The trial was finished yielding 74 evaluable patients, including 38 in the CK arm. Adverse events were infrequent and the treatment was well tolerated. The overall treatment time was significantly shorter in the CK arm (median of 13 days vs 25 days). At two years, more than half of the patients reported improvement (46; 62.2 %) , in 21 cases the pain symptoms were stable (28.4 %), and in seven cases worse (9.5 %). There were significantly more patients reporting improvement in the CK arm (73.7 % vs 50 %; p = 0.036). The median decrease in NRS was 4 (IQR 1-5) or 59 % (IQR 20-86 %), and the difference between arms was not statistically significant. CONCLUSION: Five fractions hypofractionated radiotherapy for painful vertebral haemangiomas up to a total dose of 25 Gy is a safe treatment modality, significantly shorter compared to conventional fractionation, and possibly more effective.

Mirogabalin Decreases Pain-like Behaviours and Improves Opioid and Ketamine Antinociception in a Mouse Model of Neuropathic Pain.

Neuropathic pain remains a difficult clinical challenge due to its diverse aetiology and complex pathomechanisms, which are yet to be fully understood. Despite the variety of available therapies, many patients suffer from ineffective pain relief; hence, the search for more efficacious treatments continues. The new gabapentinoid, mirogabalin has recently been approved for clinical use. Although its main mechanism of action occurs at the α2σ-1 and α2σ-2 subunits of calcium channels and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level has not been clarified, which is crucial information from a clinical perspective. The findings of our study suggest that several indirect mechanisms may be responsible for the beneficial analgesic effect of mirogabalin. This is the first study to report that mirogabalin enhances the mRNA expression of spinal antinociceptive factors, such as IL-10 and IL-18BP, and reduces the concentration of the pronociceptive substance P. Importantly, mirogabalin improves the morphine-, buprenorphine-, oxycodone-, and ketamine-induced antinociceptive effects in a neuropathic pain model. Our findings support the hypothesis that enhancing opioid and ketamine analgesia by combining these drugs with mirogabalin may represent a new strategy for the effective pharmacotherapy of neuropathic pain.

The role of complementary and alternative methods in the treatment of pain in patients with cancer - current evidence and clinical practice: a narrative review.

INTRODUCTION: Pain related to cancer, despite the numerous treatment options available, is still a challenge in contemporary pain medicine. The unsatisfactory treatment of cancer pain is one of the main reasons why patients seek complementary and alternative methods (CAM) and a more integrative/holistic approach to pain management. The popularity of CAM forces healthcare professionals to provide patients with current and evidence-based information on the effectiveness and safety of CAM. The aim of the paper is to present current evidence and limitations regarding CAM commonly used in the pain management of cancer patients. MATERIAL AND METHODS: The paper comprehensively reviews the current and most relevant literature considering the integrative approach to management of pain due to cancer disease and/or cancer treatment. RESULTS: The available data from clinical trials, meta-analyses, and systematic reviews supports the effectiveness of acupuncture, massage, physical exercises, music therapy, and mind-body therapies as adjunct therapies for alleviating pain in cancer patients, although the supporting evidence is weak or moderate. CONCLUSIONS: Based on the available knowledge, physicians should be capable of advising the cancer patient as to which CAM methods can be used safely, which are contraindicated, and what therapeutic effects they may expect, especially when standard pain treatment fails or induces serious side effects. An integrative approach to cancer pain management may improve the quality of pain treatment, patients' quality of life, and satisfaction with pain relief.

Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review.

Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients' quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences. Moreover, topical treatments applied locally may target the underlying mechanisms of peripheral sensitization and pain. Recent studies showed that peripheral sensitization results from interactions between neuronal and non-neuronal cells, with numerous signaling molecules and molecular/cellular targets involved. This narrative review discusses the molecular/cellular mechanisms of drugs available in topical formulations utilized in clinical practice and their effectiveness in clinical studies in patients with peripheral neuropathic pain. We searched PubMed for papers published from 1 January 1995 to 30 November 2020. The key search phrases for identifying potentially relevant articles were "topical AND pain", "topical AND neuropathic", "topical AND treatment", "topical AND mechanism", "peripheral neuropathic", and "mechanism". The result of our search was 23 randomized controlled trials (RCT), 9 open-label studies, 16 retrospective studies, 20 case (series) reports, 8 systematic reviews, 66 narrative reviews, and 140 experimental studies. The data from preclinical studies revealed that active compounds of topical treatments exert multiple mechanisms of action, directly or indirectly modulating ion channels, receptors, proteins, and enzymes expressed by neuronal and non-neuronal cells, and thus contributing to antinociception. However, which mechanisms and the extent to which the mechanisms contribute to pain relief observed in humans remain unclear. The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series. For topical ketamine and baclofen, data supporting their effectiveness are provided by both single RCTs and case series. The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy.

Mirogabalin-A Novel Selective Ligand for the α2δ Calcium Channel Subunit.

The efficacy of neuropathic pain control remains unsatisfactory. Despite the availability of a variety of therapies, a significant proportion of patients suffer from poorly controlled pain of this kind. Consequently, new drugs and treatments are still being sought to remedy the situation. One such new drug is mirogabalin, a selective ligand for the α2δ subunits of voltage-gated calcium channels (VGCC) developed by Sankyo group for the management of neuropathic pain. In 2019 in Japan, mirogabalin was approved for peripheral neuropathic pain following the encouraging results of clinical trials conducted with diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) patients. The ligand selectivity of mirogabalin for α2δ-1 and α2δ-2 and its slower dissociation rate for α2δ-1 than for α2δ-2 subunits of VGCC may contribute to its strong analgesic effects, wide safety margin, and relatively lower incidence of adverse effects compared to pregabalin and gabapentin. This article discusses the mechanism of action of mirogabalin, presents data on its pharmacodynamics and pharmacokinetics, and reviews the available experimental and clinical studies that have assessed the efficacy and safety of the drug in the treatment of selected neuropathic pain syndromes.

Peripheral Mechanisms of Neuropathic Pain-the Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain.

Neuropathic pain in humans arises as a consequence of injury or disease of somatosensory nervous system at peripheral or central level. Peripheral neuropathic pain is more common than central neuropathic pain, and is supposed to result from peripheral mechanisms, following nerve injury. The animal models of neuropathic pain show extensive functional and structural changes occurring in neuronal and non-neuronal cells in response to peripheral nerve injury. These pathological changes following damage lead to peripheral sensitization development, and subsequently to central sensitization initiation with spinal and supraspinal mechanism involved. The aim of this narrative review paper is to discuss the mechanisms engaged in peripheral neuropathic pain generation and maintenance, with special focus on the role of glial, immune, and epithelial cells in peripheral nociception. Based on the preclinical and clinical studies, interactions between neuronal and non-neuronal cells have been described, pointing out at the molecular/cellular underlying mechanisms of neuropathic pain, which might be potentially targeted by topical treatments in clinical practice. The modulation of the complex neuro-immuno-cutaneous interactions in the periphery represents a strategy for the development of new topical analgesics and their utilization in clinical settings.

Effect of intravenous, perioperative-administered lidocaine on serum levels of endocannabinoids and related N-acylethanolamines in children.

BACKGROUND: Endocannabinoids and N-acylethanolamines (NAEs) are compounds that play a significant role in nociception. The promising therapeutic opportunities in postoperative pain management are connected with intra-venous (i.v.) lidocaine administration as a part of multimodal analgesia. Therefore, we analyzed the influence of perioperative, i.v. lidocaine infusion in children on postoperative serum concentrations of endocannabinoids and NAEs. METHODS: Forty-four children undergoing extensive spinal surgery were divided into two groups: the lidocaine group (LG; N.=23), anesthetized generally with lidocaine as a co-analgesic, and the non-lidocaine group (NLG; N.=21), anesthetized generally without lidocaine. We also recruited 23 healthy age- and gender-matched children to the control group. Blood samples were collected before surgery, immediately after surgery, at six hours, and following morning after surgery, while in healthy children we collected blood samples only once. The serum concentrations of endocannabinoids (anandamide [AEA] and 2-arachidonyl glycerol [2-AG]) and NAEs (palmitoylethanolamide [PEA] and oleoylethanolamide [OEA]) were quantified by ultra-high-performance liquid chromatography-mass spectrometry. RESULTS: The concentrations of measured compounds were comparable in controls and in patients before surgery (all P>0.05). During the postoperative period, we found significantly higher AEA and lower 2-AG concentrations in the LG when compared to the NLG. The highest concentration of PEA was observed in LG patients six hours after the operation and, at that time it was significantly elevated when compared to the NLG (P=0.0003). CONCLUSIONS: Perioperative, i.v. lidocaine administration influences postoperative serum concentrations of endocannabinoids and NAEs in children.

Bone Pain in Cancer Patients: Mechanisms and Current Treatment.

The skeletal system is the third most common site for cancer metastases, surpassed only by the lungs and liver. Many tumors, especially those of the breast, prostate, lungs, and kidneys, have a strong predilection to metastasize to bone, which causes pain, hypercalcemia, pathological skeletal fractures, compression of the spinal cord or other nervous structures, decreased mobility, and increased mortality. Metastatic cancer-induced bone pain (CIBP) is a type of chronic pain with unique and complex pathophysiology characterized by nociceptive and neuropathic components. Its treatment should be multimodal (pharmacological and non-pharmacological), including causal anticancer and symptomatic analgesic treatment to improve quality of life (QoL). The aim of this paper is to discuss the mechanisms involved in the occurrence and persistence of cancer-associated bone pain and to review the treatment methods recommended by experts in clinical practice. The final part of the paper reviews experimental therapeutic methods that are currently being studied and that may improve the efficacy of bone pain treatment in cancer patients in the future.

Impact of Intravenous, Perioperative-Administrated Lidocaine on Postoperative Serum Levels of Endogenous Opioids in Children.

BACKGROUND: Endogenous opioids are neuropeptides involved in pain-relieving processes. In the periphery, they are synthesised and stored in cells of the immune system. OBJECTIVE: In the current study, we describe the influence of perioperative, intravenous (i.v.) lidocaine infusion in children on postoperative, serum endogenous opioid concentrations in children. METHODS: Forty-four children undergoing major spinal surgery were enrolled in the cohort study. They were divided into two groups: group A (n = 21) generally anesthetised with fentanyl, propofol, rocuronium, a mixture of oxygen/air/sevoflurane and with analgetics and co-analgetics: morphine, acetaminophen, metamizole, gabapentin, dexamethason and group B (n = 23) where, in addition to the above-described general anesthesia, patients were given i.v. lidocaine as a co-analgesic. We also recruited 20 healthy age- and gender-matched children (group C). We measured endogenous opioid levels in serum using immunoenzymatic methods. We evaluated postoperative pain intensity using a numerical or visual pain scale and demand for morphine. RESULTS: The levels of measured endogenous opioids were similar in the control and in the studied groups before surgery. We noted that group B patients had lower pain intensity when compared to group A subjects. In group B, the elevated serum concentrations of ß-endorphin, enkephalin and dynorphin in the postoperative period were reported. We also observed that the levels of endogenous opioids negatively correlated with morphine requirements and positively correlated with lidocaine concentration. CONCLUSION: Multidrug pain management including lidocaine seems to be more efficient than models without lidocaine. The endogenous opioid system should be considered as a novel target for pain relief therapy in children.

Mechanisms of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating this syndrome are very limited. There are six main substance groups that cause damage to peripheral sensory, motor and autonomic neurons, which result in the development of CIPN: platinum-based antineoplastic agents, vinca alkaloids, epothilones (ixabepilone), taxanes, proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide). Among them, the most neurotoxic are platinum-based agents, taxanes, ixabepilone and thalidomide; other less neurotoxic but also commonlyused drugs are bortezomib and vinca alkaloids. This paper reviews the clinical picture of CIPN and the neurotoxicity mechanisms of the most common antineoplastic agents. A better understanding of the risk factors and underlying mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies.

Pharmacotherapy of pain in cancer patients - recommendations of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons.

Guidelines for the pharmacotherapy of pain in cancer patients were developed by a group of 21 experts of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons. During a series of meetings, the experts carried out an overview of the available literature on the treatment of pain in cancer patients, paying particular attention to systematic reviews and more recent randomized studies not included in the reviews. The search was performed in the EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials databases using such keywords as "pain", "cancer", "pharmacotherapy", "analgesics", and similar. The overviewed articles included studies of pathomechanisms of pain in cancer patients, methods for the assessment of pain in cancer patients, and drugs used in the pharmacotherapy of pain in cancer patients, including non-opioid analgesics (paracetamol, metamizole, non-steroidal anti-inflammatory drugs), opioids (strong and weak), coanalgesics (glucocorticosteroids, α2-adrenergic receptor agonists, NMDA receptor antagonists, antidepressants, anticonvulsants, topical medications) as well as drugs used to reduce the adverse effects of the analgesic treatment and symptoms other than pain in patients subjected to opioid treatment. The principles of opioid rotation and the management of patients with opioidophobia were discussed and recommendations for the management of opioid-induced hyperalgesia were presented. Drugs used in different types of pain experienced by cancer patients, including neuropathic pain, visceral pain, bone pain, and breakthrough pain, were included in the overview. Most common interactions of drugs used in the pharmacotherapy of pain in cancer patients as well as the principles for the management of crisis situations. In the final part of the recommendations, the issues of pain and care in dying patients are discussed. Recommendations are addressed to physicians of different specialties involved in the diagnostics and treatment of cancer in their daily practice. It is the hope of the experts who took part in the development of these recommendations that the recommendations would become helpful in everyday medical practice and thus contribute to the improvement in the quality of care and the efficacy of pain treatment in this group of patients.

Perioperative Immunosuppression and Risk of Cancer Progression: The Impact of Opioids on Pain Management.

Opioids comprise an important group of drugs used in cancer pain pharmacotherapy. In recent years, more and more studies have emerged indicating the potentially immunosuppressive effects of opioid analgesics and their serious consequences, including the risk of cancer progression. The identification of these risks has prompted a search for other effective, and most importantly, safer methods of perioperative analgesic management. Regional analgesia techniques, which allow for a significant reduction in opioid dosing and thus diminish the risk of immunosuppression associated with these drugs, seem to offer substantial hope in this respect. A number of studies available in the literature assess the effects of regional analgesia techniques on cancer progression; however, it is often difficult to interpret their results owing to several perioperative factors (such as surgical trauma, inadequate pain and stress relief, and hypothermia) which are also attributed immunosuppressive effects and tend to be implicated in increased risk of cancer progression. Further research is needed to verify the available data on both the potential adverse effects of opioids and the possible protective effects of regional analgesia techniques on cancer patients.

Tapentadol - A representative of a new class of MOR-NRI analgesics.

Tapentadol is a centrally acting analgesic with a dual mode of action as a µ-opioid receptor (MOR) agonist and a noradrenaline reuptake inhibitor (NRI). It was initially approved by the US Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients, and in August 2011, for chronic pain in an prolonged release form in the same population. Due to its limited protein binding capacity, the absence of active metabolites and significant microsomal enzyme induction or inhibition, tapentadol has a limited potential for drug-drug interactions. It appears to be well-tolerated and effective in the treatment of moderate-to severe acute and chronic pain. Owing to its dual mechanism of action, it is hypothesized to be good option in the treatment of both nociceptive and neuropathic pain.

Pain chronification: what should a non-pain medicine specialist know?

OBJECTIVE: Pain is one of the most common reasons for an individual to consult their primary care physician, with most chronic pain being treated in the primary care setting. However, many primary care physicians/non-pain medicine specialists lack enough awareness, education and skills to manage pain patients appropriately, and there is currently no clear, common consensus/formal definition of "pain chronification". METHODS: This article, based on an international Change Pain Chronic Advisory Board meeting which was held in Wiesbaden, Germany, in October 2016, provides primary care physicians/non-pain medicine specialists with a narrative overview of pain chronification, including underlying physiological and psychosocial processes, predictive factors for pain chronification, a brief summary of preventive strategies, and the role of primary care physicians and non-pain medicine specialists in the holistic management of pain chronification. RESULTS: Based on currently available evidence, we propose the following consensus-based definition of pain chronification which provides a common framework to raise awareness among non-pain medicine specialists: "Pain chronification describes the process of transient pain progressing into persistent pain; pain processing changes as a result of an imbalance between pain amplification and pain inhibition; genetic, environmental and biopsychosocial factors determine the risk, the degree, and time-course of chronification." CONCLUSIONS: Early intervention plays an important role in preventing pain chronification and, as key influencers in the management of patients with acute pain, it is critical that primary care physicians are equipped with the necessary awareness, education and skills to manage pain patients appropriately.

Transcranial direct current stimulation (tDCS) and its influence on analgesics effectiveness in patients suffering from migraine headache.

BACKGROUND: Headache is one of the most common conditions troubling nearly 45% of the world's population. Migraine headache itself, being more common among women, affects 7-18% of people. As much as 20-30% of the population report accompanying aura and neurological symptoms. In many cases, migraine headache can be effectively treated with suitably selected pharmacotherapies which include drugs used in symptomatic treatment. Frequent occurrence of the condition is treated with prophylaxis, which often fails. Neuromodulating methods are part of the multidirectional treatment and they may be valuable complement to pharmacotherapy. METHODS: Our study evaluates the impact of the transcranial direct current stimulation (tDCS) on the consumption of drugs and on pain conditions (frequency, duration, intensity). We recruited 50 patients with migraine headache (30 with aura, 20 without aura) refractory to pharmacological therapy. In 30 patients (18 with aura, 12 without aura) previous unsatisfactory treatment was supplemented with tDCS performed tenfold. 20 patients (12 with aura, 8 without aura) from a control group were treated with pharmacological methods The observation continued for 30 days after the stimulation. RESULTS: After tDCS, a reduction in the consumption of analgesics and triptans was reported. Additionally, we monitored pain intensity decrease during pain episodes, duration of episodes and the number of pain days. The subjective assessment of pain reduction in migraine patients encompassed 36-40% after tDCS much more effective in comparison to group with only pharmacotherapy (10-12.5%). CONCLUSIONS: The study suggests that tDCS may be safe and useful clinical tool in migraine prophylaxis and treatment.

Treatment for chronic low back pain: the focus should change to multimodal management that reflects the underlying pain mechanisms.

Chronic low back pain: Chronic pain is the most common cause for people to utilize healthcare resources and has a considerable impact upon patients' lives. The most prevalent chronic pain condition is chronic low back pain (CLBP). CLBP may be nociceptive or neuropathic, or may incorporate both components. The presence of a neuropathic component is associated with more intense pain of longer duration, and a higher prevalence of co-morbidities. However, many physicians' knowledge of chronic pain mechanisms is currently limited and there are no universally accepted treatment guidelines, so the condition is not particularly well managed. DIAGNOSIS: Diagnosis should begin with a focused medical history and physical examination, to exclude serious spinal pathology that may require evaluation by an appropriate specialist. Most patients have non-specific CLBP, which cannot be attributed to a particular cause. It is important to try and establish whether a neuropathic component is present, by combining the findings of physical and neurological examinations with the patient's history. This may prove difficult, however, even when using screening instruments. Multimodal management: The multifactorial nature of CLBP indicates that the most logical treatment approach is multimodal: i.e. integrated multidisciplinary therapy with co-ordinated somatic and psychotherapeutic elements. As both nociceptive and neuropathic components may be present, combining analgesic agents with different mechanisms of action is a rational treatment modality. Individually tailored combination therapy can improve analgesia whilst reducing the doses of constituent agents, thereby lessening the incidence of side effects. CONCLUSIONS: This paper outlines the development of CLBP and the underlying mechanisms involved, as well as providing information on diagnosis and the use of a wide range of pharmaceutical agents in managing the condition (including NSAIDs, COX-2 inhibitors, tricyclic antidepressants, opioids and anticonvulsants), supplemented by appropriate non-pharmacological measures such as exercise programs, manual therapies, behavioral therapies, interventional pain management and traction. Surgery may be appropriate in carefully selected patients.