Jan Dobrogowski

Do strong opioids have a role in the early management of back pain? Recommendations from a European expert panel

ABSTRACT Background: Since chronic low back pain (CLBP) is a complex biopsychosocial problem the ideal treatment is multimodal and multidisciplinary. However, in many countries, primary-care physicians care for many people with CLBP and have a pivotal role in selecting patients for more intensive treatments when these are available. Guidelines on the general use of strong opioids in chronic non-cancer pain have been published but, until now, no specific guidelines were available on their use in chronic low back pain. Given the prevalence of CLBP, and the complex nature of this multifactorial condition, it was felt that specific, evidence-based recommendations, with a focus on primary-care treatment, would be helpful. Methods: An expert panel drawn from across Europe including pain specialists, anaesthetists, neurologists, rheumatologists, a general practitioner, an epidemiologist and the chairman of a pain charity was therefore convened. The aim of the group was to develop evidence-based recommendations that could be used as a framework for more specific guidelines to reflect local differences in the availability of specialist pain services and in the legal status and availability of strong opioids. Statements were based on published evidence (identified by a literature search) wherever possible, and supported by clinical experience when suitable evidence was lacking. Recommendations: Strong opioids have a role in the treatment of low back pain when other treatments have failed. They should be prescribed as part of a multimodal, and ideally interdisciplinary, treatment plan. The aim of treatment should be to relieve pain and facilitate rehabilitation.

Tapentadol in the management of chronic low back pain: A novel approach to a complex condition?

Chronic pain affects approximately 1 in 5 people in Europe, and around half of sufferers receive inadequate pain management. The most common location is the lower back. Pharmacological treatment of this condition is challenging because of the range of causative mechanisms and the difficulty of balancing analgesic efficacy and tolerability. An international panel of clinical pain specialists met in September, 2009, to discuss the treatment of chronic low back pain, and to review preclinical and clinical data relating to the new analgesic, tapentadol. A lack of consensus exists on the best treatment for low back pain. The range of regularly prescribed pharmacological agents extends from nonopioids (paracetamol, NSAIDs, and COX-2 inhibitors) to opioids, antidepressants and anticonvulsants. Pain relief may be compromised, however, by an undetected neuropathic component or intolerable side effects. Treatment is potentially life-long and effective analgesics are urgently needed, with demonstrable long-term safety. Combining separate agents with different mechanisms of action could overcome the limitations of present pharmacological therapy, but clinical evidence for this approach is currently lacking. Tapentadol combines μ-opioid agonism with noradrenaline reuptake inhibition in a single molecule. There is strong evidence of synergistic antinociception between these two mechanisms of action. In preclinical and clinical testing, tapentadol has shown efficacy against both nociceptive and neuropathic pain. Preclinical data indicate that tapentadol’s μ-opioid agonism makes a greater contribution to analgesia in acute pain, while noradrenaline reuptake inhibition makes a greater contribution in chronic neuropathic pain models. Tapentadol also produces fewer adverse events than oxycodone at equianalgesic doses, and thus may have a ‘μ-sparing effect’. Current evidence indicates that tapentadol’s efficacy/tolerability ratio may be better than those of classical opioids. However, further research is needed to establish its role in pain management.

Diagnosis and management of neuropathic pain: review of literature and recommendations of the Polish Association for the study of pain and the Polish Neurological Society - part one.

Neuropathic pain may be caused by a variety of lesions or diseases of both the peripheral and central nervous system. The most common and best known syndromes of peripheral neuropathic pain are painful diabetic neuropathy, trigeminal and post-herpetic neuralgia, persistent post-operative and post-traumatic pain, complex regional pain syndrome, cancer-related neuropathic pain, HIV-related neuropathic pain and pain after amputation. The less common central pain comprises primarily central post-stroke pain, pain after spinal cord injury, central pain in Parkinson disease or in other neurodegenerative diseases, pain in syringomyelia and in multiple sclerosis. A multidisciplinary team of Polish experts, commissioned by the Polish Association for the Study of Pain and the Polish Neurological Society, has reviewed the literature on various types of neuropathic pain, with special focus on the available international guidelines, and has formulated recommendations on their diagnosis and treatment, in accordance with the principles of evidence-based medicine (EBM). High quality studies on the efficacy of various medicines and medical procedures in many neuropathic pain syndromes are scarce, which makes the recommendations less robust.

Transdermal buprenorphine for the treatment of moderate to severe chronic pain: results from a large multicenter, non-interventional post-marketing study in Poland

Abstract Objective: To evaluate the use of a buprenorphine transdermal patch (Transtec) in routine clinical practice, including dosage, indications, efficacy and tolerability. Research design and methods: This prospective, open-label, non-comparative, non-interventional, post-marketing study was performed in Poland by 339 investigators in a range of clinical practice settings. Patients with chronic moderate to severe cancer pain, or chronic severe non-cancer pain that was insufficiently controlled by non-opioids, were prescribed buprenorphine transdermal patch 35, 52.5 or 70 μg/hour (changed twice weekly), and followed up for 3 months. Additional analgesia, and adjuvant/supportive treatments were allowed at the discretion of the physician. Main outcome measures: The study enrolled 4030 patients, with a mean age of 62.8 years. Most patients had cancer-related pain (80.7%). Non-cancer pain was generally musculoskeletal or neuropathic. A starting dose of 35, 52.5 or 70 μg/hour was used in 73.4%, 21.5%, and 4.8% of patients, respectively. Buprenorphine dose was increased in 44.7% of patients during the observation, generally from 35 to 52.5 μg/hour. Mean pain intensity (using a 100 mm visual analogue scale) decreased by 73.5% from 62.3 mm at baseline to 16.5 mm after 3 months. Most patients rated pain relief as ‘very good’ (41.4%) or ‘good’ (44.5%). Sleep quality also improved. 48.1% of patients needed no additional analgesics during buprenorphine treatment. Most patients (96%) rated the buprenorphine transdermal patch as ‘very easy’ or ‘easy’ to change. The most common treatment-related reasons for discontinuation were lack of analgesic effect (3.3% of patients) and adverse drug reactions (ADRs, 0.8%). ADRs, all non-serious, occurred in 34 patients (0.8%), most commonly local skin reactions or vomiting. At study end, it was planned to continue treatment with transdermal buprenorphine in 70.1% of patients. The main limitations related to the observational study design, balanced by advantages gained from the ‘real life’ exploration of transdermal buprenorphine use. Conclusions: In routine Polish clinical practice, transdermal buprenorphine was effective and generally well-tolerated in patients with chronic moderate to severe cancer pain or chronic severe non-malignant pain insufficiently controlled by non-opioids.

Transdermal buprenorphine in the treatment of cancer and non-cancer pain - the results of multicenter studies in Poland.

This was a multicenter, non-interventional, post-marketing study that aimed to evaluate the analgesic activity, safety of use, safety profile and adverse drug reactions of transdermal buprenorphine (Transtec 35, 52.5 and 70 μg/h) during the treatment of moderate to severe chronic cancer and non-cancer pain. The study was performed in Poland by 339 doctors. The study involved 4,030 general practice outpatients (managed by primary care physicians), pain therapy center patients, specialist outpatient clinic patients as well as patients treated in inpatients units. The recruitment process began in September of 2007, and the study was completed in October of 2008. The study has been reported to the Central Register of Clinical Trials in Poland; it was also in accordance with the requirements of the Polish Pharmaceutical Law in force. The objective of the study was to evaluate the efficacy, safety of use and application of transdermal buprenorphine in patients with moderate to severe cancer pain and in patients with severe, non-malignant pain in the course of other diseases. Patients were enrolled if their pain was not well-controlled after using non-opioid analgesics. Another objective of the study was to monitor adverse drug reactions of transdermal buprenorphine reported by patients or noted by the doctors during the study visits. This first such multicenter study in Poland has confirmed high efficacy and good tolerability of buprenorphine and, therefore, confirmed its usefulness in the treatment of moderate to severe cancer pain as well as in the treatment of severe pain in patients with non-cancer pain that cannot be effectively treated with non-opioid analgesics.

Validation and cross-cultural adaptation of the Polish version of the Oswestry Disability Index.

Study Design. Validation of a translated, culturally adapted questionnaire. Objective. To translate and culturally adapt a Polish version of the Oswestry Disability Index (ODI) and to validate its use in Polish patients. Summary of Background Data. The ODI is among the most popular questionnaires used to evaluate back pain–related disability. To our knowledge no validated Polish version of the index was available at the time our study was initiated. Methods. The questionnaire was translated and culturally adapted by 2 independent translators and approved by expert committee. Final version was included in the booklet consisting in addition of a previously validated Roland–Morris disability questionnaire, VAS for low back and leg and 3 Likert scale questions (pain medications, pain frequency, disability). It was tested on 169 patients with chronic low back pain, 164 (97%) of them were enrolled, and 84 of 164 (53%) returned the completed retest booklet within 2 to 14 days after the baseline test. There were no differences between the 2 groups in demographic and clinical parameters. Test-retest reliability, internal consistency, and construct validity were investigated. Results. The mean ODI (standard deviation [SD]) was 48.45 (18.94); minimum 2, maximum 94. The Cronbach &agr; for baseline questionnaires (n = 164) was 0.90. Concurrent validity, measured by comparing ODI responses with the results of the Roland–Morris disability questionnaire score was very good (r = 0.607, P < 0.001). The correlation with VAS back was fair (r = 0.37, P < 0.001) and with VAS leg was good (r = 0.56, P < 0.001). The tested ODI had excellent test-retest reliability, the intraclass correlation coefficient was 0.97 and standard error of measurements was 3.54, the resulting minimal detectable changes at the 95% confidence level was 10. Conclusion. The results of this study indicate that the Polish version of the ODI is a reliable and valid instrument for the measurement of disability in Polish-speaking patients with lower back pain.

Peripheral opioid analgesia in laparoscopic cholecystectomy.

Background Recent research has revealed that opioids can act directly on the peripheral terminals of afferent nerves to mediate antinociception. The aim of this study was to assess the influence of peripheral morphine administration on the nociception process in the postoperative period. Methods One hundred fifty patients for laparoscopic cholecystectomy were randomly divided into 5 groups. Group M patients (n = 30) received local infiltration at trocar insertion points with 2 mg morphine in 20 mL of 0.9% NaCl solution (5 mL of solution per point) 10 minutes before the operation. For group B patients (n = 30), the solution used for infiltration was 20 mL of 0.25% bupivacaine; for group M+B patients (n = 30), the solution was 2 mg morphine in 20 mL of 0.25% bupivacaine; and for group S patients (n = 30), the solution was 20 mL 0.9% NaCl. For group S+M patients (n = 30), trocar insertion points were infiltrated with 20 mL of 0.9% NaCl, and patients in this group were given 2 mg of subcutaneous morphine 10 minutes before the surgery. Postoperative analgesic therapy was provided by on-demand analgesia with tramadol. After surgery, the following were measured: pain intensity scored on the visual analog scale, total tramadol requirement, time from the end of the surgical procedure to the administration of the first dose of tramadol, and the frequency of undesirable side effects (sedation, nausea, and vomiting). Results Pain intensity and total tramadol requirement after surgery were lower in groups M, B, and M+B compared with groups S and S+M, but these differences were not statistically significant. The time from the completion of the operation to the administration of the first dose of tramadol was significantly longer in groups M, B, and M+B compared with groups S and S+M. Conclusion Results of the study confirm the possibility of modifying the nociception process in the postoperative period through peripheral opioid administration.

Intravenous lidocaine infusions in a multidirectional model of treatment of neuropathic pain patients

BACKGROUND Neuropathic pain, is caused by damage or disease affecting the somatosensory nervous system, leads to deterioration of the quality of life of patients. Most commonly, this deterioration is due to the inefficacy of treatment or to the adverse effects of systemic treatment. Pharmacotherapy of neuropathic pain involves the use of antiepileptic agents, antidepressants, and opioids that may lead to numerous adverse effects, particularly in elderly patients. Intravenous infusions of lidocaine may improve the efficacy of the analgesic treatment of neuropathic pain patients while not causing any significant adverse effects. METHODS In our study, we carried out a retrospective analysis of 85 patients with various neuropathic pain syndromes. In this group, 81 patients received 3-25 intravenous infusions of lidocaine (5mg/kg of body weight over 30min). In the remaining 4 patients, the treatment was discontinued after the first infusion due to the lack of efficacy. RESULTS The analgesic effect of intravenous lidocaine was better when the intensity of pain experienced before the infusion was high. In addition, better effects were observed in elderly patients. No need to interrupt the infusion occurred in any of the patients. No serious adverse effects were observed either. Transient dizziness, not requiring additional treatment, occurred in 5 patients after the infusion. CONCLUSIONS The best therapeutic effects of lidocaine infusion was observed in pain symptoms characterized by the highest intensity of baseline pain. Intravenous lidocaine administered at the dose of 5mg/kg of body weight over 30min is effective, safe and caused no significant adverse effects.

Non-invasive transcutaneous Supraorbital Neurostimulation (tSNS) using Cefaly® device in prevention of primary headaches

Headaches are one of the most common pain syndromes experienced by adult patients. International Classification of Headache Disorders identifies about 300 different entities. Primary headaches (migraine, tension-type headache, trigeminal autonomic cephalalgias, other primary headaches) has the common occurrence. Although effective treatment of these disorders is possible, it is inefficient or poorly tolerated in some patients. Neuromodulation methods, being element of multimodal treatment, provide an additional treatment option in pharmacotherapy-refractory patients. Both invasive and non-invasive stimulation methods are used. The non-invasive techniques is transcutaneous nerve stimulation using Cefaly® device. In this study, Cefaly® was used as prevention treatment in patients with pharmacotherapy-refractory headaches. This device is indicated for the prophylactic treatment of episodic primary headaches. A total of 91-patients (30 without and 61 with tSNS) were enrolled in the study, including 60-patients with migraine and 31-patients with other primary headaches. Ten courses of non-invasive peripheral (supraorbitral/supratrochlear) nerves stimulation were delivered to 57-patients; in the remaining 4 patients, the treatment was abandoned due to poor tolerance. Patients were observed for 30 days after stimulation treatment. Compared to the pre-treatment period, the reduction in the intensity of pain was observed in both the migraine group and patients with other types of headaches; this included the number of pain episodes being reduced by half, with simultaneous reduction in average pain intensity and duration of individual pain episodes. The subjective assessment of pain reduction was in the range of 40-47%. Based on our data we recommend tSNS as useful tool in the prophylaxis of primary headaches, including migraine.

ORIGINAL ARTICLE: The Increase in Metallothionein and Ectopic Decidual Immunoreactivity with Respect to the Progression of Labor at Term and the Lack of Analogical Changes in Placental Abruption

Problem  The coexistence of immune and decidual cells is related to the development of a resistance to immune‐mediated apoptosis in both ectopic and eutopic decidua. This unique feature of endometrial cells seems to be linked with the expression of metallothionein (MT), an inhibitor of apoptosis.