Shedding light on neuropathic pain: Current and emerging tools for diagnosis, screening, and quantification.

Ensuring the proper management of neuropathic pain is a contemporary challenge for professionals who care for patients with this type of pain. The estimated prevalence of neuropathic pain in Europe is 7%-8%. The objective of this study was to perform a non-systematic review on the diagnosis, screening, and quantification of neuropathic pain. For this purpose, a search was conducted of the PubMed/Medline, ScienceDirect, OVID, and SciELO databases for available evidence. The findings highlight the common occurrence of chronic neuropathic pain in clinical practice. However, diagnosing and managing this type of pain pose challenges due to its complexity and the individualized nature of cases. Precise diagnosis is crucial for effective management, involving therapeutic approaches that go beyond traditional pain treatments. It is noteworthy that until recent times, general questionnaires were utilized to assess neuropathic pain, lacking the ability to distinguish it from nociceptive pain or evaluate its broader impact on well-being. Biomarker pain panels hold promise in identifying treatable pain causes and evaluating treatment effectiveness. In conclusion, this review describes the diagnostic methods and tools for screening and quantifying neuropathic pain.

Off-label pharmacological treatment for neuropathic pain: A Delphi study by the Spanish Pain Society Neuropathic Pain Task Force.

OBJECTIVES: The use of off-label pharmacotherapies for neuropathic pain (NP) is growing relating to the many unmet needs of patients. However, clinical guidelines fail to address it, and the available evidence is sparse and fragmented. We arranged a formal expert consensus to address this controversial issue and provide some guidance on judicious use. METHODS: A two-round standard Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 40-item questionnaire prepared by the authors. Consensus on each statement was defined as at least either 80% endorsement or rejection after the second round. RESULTS: Forty-three and thirty-seven panelists participated in the first and second round, respectively. Consensus was reached in 34 out of 40 statements. Endorsed alternatives for unresponsive patients include non-gabapentinoid antiepileptics (oxcarbazepine and eslicarbazepine), venlafaxine, intravenous lidocaine (when doses can be optimized), and some vaporized cannabinoids (under appropriate surveillance). In addition, lacosamide, low-dose naltrexone, propofol, or ketamine could prove beneficial if subjected to more research. Other options were rejected, and there was controversy about the usefulness of topical preparations. DISCUSSION: For patients who do not respond to standard NP treatments, some other viable pharmacological options can be attempted before advancing to other therapeutic stages. This may help patients who are reluctant to or have some contraindication for interventional therapies.

Update on Interventional Management of Neuropathic Pain: A Delphi Consensus of the Spanish Pain Society Neuropathic Pain Task Force.

Background and Objectives: Interventional management of neuropathic pain (NP) is available to the patients who do not obtain satisfactory pain relief with pharmacotherapy. Evidence supporting this is sparse and fragmented. We attempted to summarize and critically appraise the existing data to identify strategies that yield the greatest benefit, guide clinicians, and identify areas that merit further investigation. Material and Methods: A two-round Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 26-item questionnaire made by the authors. Consensus on each statement was defined as either at least 80% endorsement or rejection after the 2nd round. Results: Thirty-five and 29 panelists participated in the 1st and 2nd round, respectively. Consensus was reached in 20 out of 26 statements. There is sufficient basis to treat postherpetic neuralgias and complex regional pain syndromes with progressive levels of invasiveness and failed back surgery syndrome with neuromodulation. Radiculopathies and localized NP can be treated with peripheral blocks, neuromodulation, or pulsed radiofrequency. Non-ablative radiofrequency and non-paresthetic neuromodulation are efficacious and better tolerated than ablative and suprathreshold procedures. Conclusions: A graded approach, from least to most invasive interventions has the potential to improve outcomes in many patients with common refractory NP conditions. Preliminary promising data warrant further research on new indications, and technical advances might enhance the safety and efficacy of current and future therapies.

ANALGESIC EFFICACY OF TRAMADOL/DEXKETOPROFEN VS IBUPROFEN AFTER IMPACTED LOWER THIRD MOLAR EXTRACTION: A RANDOMIZED CONTROLLED CLINICAL TRIAL.

OBJECTIVE: Impacted third molar extraction is associated with acute moderate-to-severe pain for up to 48 hours post-surgery. This trial was designed to compare the analgesic effectiveness, swelling, and adverse events after impacted third molar surgery following multimodal therapy with 75 mg tramadol hydrochloride plus 25 mg dexketoprofen or monotherapy with 400 mg ibuprofen. METHODS: Seventy-two patients were randomly assigned to receiving ibuprofen (n = 36) or tramadol-dexketoprofen (n = 36). Postoperative pain intensity and swelling were measured using a visual analog scale (VAS); pain relief experienced was reported using a 4-point verbal rating scale; the rescue medication requirement, adverse effects, and global impression of the medication were recorded. RESULTS: No statistically significant between-group difference in pain intensity was observed at any time point; however, pain relief was significantly higher in the tramadol-dexketoprofen treated-group at 6 and 36 hours. Self-reported verbal rating scale assessments showed significantly lower swelling in the tramadol-dexketoprofen group at 24 hours post-surgery but not at 48 or 72 hours, and VAS-swelling scores showed no significant between-group difference. The frequency of postoperative nausea and dizziness was significantly higher in the tramadol-dexketoprofen group. CONCLUSIONS: Multimodal therapy proved more effective to manage moderate-severe pain after impacted third molar surgery in comparison to monotherapy. However, the improvement in relief must be balanced against the increased risk of adverse effects when considering this multimodal approach.

Evaluation of the Analgesic Efficacy of a Bioelectronic Device in Non-Specific Chronic Low Back Pain with Neuropathic Component. A Randomized Trial.

Low energy pulsed electromagnetic signals (PEMS) therapy, in the field of bioelectronics, has been suggested as a promising analgesic therapy with special interest in treating conditions with poor response to pharmacotherapy. This study evaluated the effectiveness of PEMS therapy on the treatment of chronic low back pain patients with a neuropathic component. A group of 64 individuals with such condition was allocated to a 2-week treatment period (10 twenty-minute sessions on consecutive days) with an active PEMS therapy device or an inactive device in random order. The pain was assessed on a visual analog scale, and the functional status was assessed using the SF-12 questionnaire. The visual analog scale scores were lower after treatment than at baseline but only in the group treated with the active device. According to the DN4 score, neuropathic pain decreased in both experimental groups with respect to baseline, but this was only significant for the group treated with the active device. Similarly, an improvement in the SF-12 and Medical Outcomes Study (MOS) sleep scale components was reported. The study demonstrated that low-energy PEMS therapy was efficient in reducing pain and improving function in chronic low back pain patients with a neuropathic component.

Organización paliativa durante la pandemia de la COVID-19 y propuestas para la adaptación de los servicios y programas de cuidados paliativos y de atención psicosocial ante la posibilidad de reactivación de la pandemia y época pos-COVID-19 / Palliative organization during the COVID-19 pandemic and proposals to adapt palliative and psychosocial care services and programs in the face of potential pandemic reactivation and the post-COVID-19 world

INTRODUCCIÓN: La irrupción brusca e intensa de la COVID-19 en nuestra sociedad ha provocado un elevado sufrimiento en pacientes y familias, así como una elevada presión en profesionales y servicios. Sus peculiares características han hecho emerger la atención paliativa como uno de los ejes principales de su abordaje. Este hecho ha provocado una reestructuración de equipos y servicios de cuidados paliativos y atención psicosocial. OBJETIVOS: Describir la respuesta inicial de diversos equipos de cuidados paliativos y atención psicosocial ante la pandemia por la COVID-19, así como elaborar una serie de recomendaciones ante la posibilidad de una nueva reactivación de la pandemia. MATERIAL Y MÉTODOS: Tras una revisión narrativa de la literatura se elaboró un cuestionario con los elementos organizativos más destacados. Este cuestionario se envió a diversos expertos y referentes en cuidados paliativos en España. En una segunda fase, y tras el análisis de los resultados del cuestionario, se elaboraron una serie de recomendaciones. RESULTADOS: Los elementos destacados de la revisión de la literatura fueron: 1) preparación y protección de equipos; 2) presencia de los cuidados paliativos en el sistema; 3) intervención en pacientes agudos; 4) desarrollo de planes asistenciales; 5) provisión de medicación esencial; 6) voluntariado; 7) docencia, y 8) participación de la sociedad. Respondieron 26 de los 31 expertos. Los resultados muestran una respuesta organizativa variable, desde implicación y liderazgo hasta reducción de estructuras, de acuerdo con su posición previa en el sistema. Dentro de las propuestas para afrontar una nueva ola de la pandemia se encuentran: 1) evaluación del estado de los equipos; 2) valorar el grado de adaptación y respuesta a la crisis; 3) conocer las nuevas necesidades; 4) promover una intervención proactiva; y 5) reprogramar los actuales planes de cuidados paliativos. CONCLUSIONES: El presente trabajo muestra la respuesta inicial global de los equipos paliativos ante la pandemia por la COVID-19 y propone una serie de recomendaciones sobre las que plantear intervenciones futuras que respondan a la futura realidad pos-COVID-19

INTRODUCTION: The sudden and intense COVID-19 outbreak has caused in our society a lot of suffering in patients and families alike, and has also put high pressure on professionals and services. Its peculiar characteristics have led to the emergence of palliative care as one of the main axes for its approach. This fact has led to a restructuring of palliative care and psychosocial care teams and services. AIMS: To describe the initial response of various palliative care and psychosocial care teams to the COVID-19 pandemic, as well as to draw up a series of recommendations regarding the possibility of a new reactivation of the pandemic. MATERIAL AND METHODS: After a narrative review of the literature, a questionnaire was prepared with the most outstanding organizational elements. This questionnaire was sent to various experts and opinion leaders in palliative care in Spain. In a second phase, and after analyzing the results of the questionnaire, a series of recommendations were issued. RESULTS: The highlighted elements of the literature review were: 1) equipment preparation and protection; 2) the presence of palliative care in the health system; 3) intervention in acute patients; 4) development of care plans; 5) provision of essential medication; 6) volunteering; 7) teaching; and 8) civil society participation. A total of 26 out of 31 experts responded. The results show a variable organizational response, from involvement and leadership to reduction of structures, according to the the position previously held in the system. Among the proposals to face a new wave of the pandemic are: 1) evaluating the state of equipments; 2) assessing the degree of adaptation and response to the crisis; 3) satisfying new needs; 4) promoting proactive intervention; and 5) reprograming current palliative care plans. CONCLUSIONS: This work shows the initial global response of palliative teams to the COVID-19 pandemic, and issues a series of recommendations on which future interventions to respond to post-COVID-19 reality should be based

Prevalence of central and peripheral neuropathic pain in patients attending pain clinics in Spain: factors related to intensity of pain and quality of life.

BACKGROUND: The objective of the study was to estimate the prevalence of pure central neuropathic pain (CNP) and peripheral neuropathic pain (PNP) among patients attending pain clinics in Spain. The study also aimed to analyze factors associated with pain intensity and quality of life (QoL). METHODS: A cross-sectional study was performed including 53 patients with pure CNP and 281 with pure PNP attending in 104 pain clinics in Spain. The revised grading system proposed in 2008 to determine a definite, probable or possible diagnosis of NP was used. Pain features, psychological variables and QoL were assessed. Descriptive, bivariate and multivariate analyses were performed. RESULTS: The prevalence of pure CNP and PNP amongst neuropathic pain patients was 2.4% (95% CI: 1.7;3.1) and 12.9% (95% CI: 1.5;14.3), respectively. Comorbid anxiety, depression or sleep disorders were high in both groups, but higher in CNP patients (51.1%, 71.4%, respectively). Pain intensity in PNP patients was associated with the presence of depression and sleep disturbances. However, in CNP patients, it was related with pain in the lower limbs. The impairment of QoL was greater in CNP patients than in PNP patients; pain location, presence of depression and sleep disturbance were the factors that most negatively affected QoL. Among PNP patients, women and those with higher pain intensity had worse QoL. CONCLUSION: Pain intensity and QoL are affected by different factors in patients suffering from CNP or PNP. Identifying these factors could serve to guide therapeutic strategies and improve the QoL of patients.

A survey of perceptions, attitudes, knowledge and practices of medical oncologists about cancer pain management in Spain

Purpose: To monitor oncologists’ perspective on cancer pain management. Methods: An anonymized survey was conducted in two waves. First, over a convenience sample of oncologists known to be particularly concerned with the management of pain. Second, using a random sample of oncologists. Results: In total, 73 and 82 oncologists participated in the first and second wave, respectively. Many oncologists reported to have good knowledge of analgesic drugs (95.9%), the mechanism of action of opioids (79.5%), and good skills to manage opioid-related bowel dysfunction (76.7%). Appropriate adjustment of background medication to manage breakthrough pain was reported by 95.5% of oncologists. Additionally, 87.7% (68.3% in the second wave, p = 0.035) of oncologists reported suitable opioid titration practices, and 90.4% reported to use co-adjuvant medications for neuropathic pain confidently. On the other hand, just 9.6% of oncologists participated in multidisciplinary pain management teams, and merely 30.3 and 27.1% reported to routinely collaborate with the Pain Clinics or involve other staff, respectively. Only 26.4% of the oncologists of the second wave gave priority to pain pathophysiology to decide therapies, and up to 75.6% reported difficulties in treating neuropathic pain. Significantly less oncologists of the second wave (82.9 vs. 94.5%, p = 0.001) used opioid rotation routinely. Conclusions: Unlike in previous surveys, medical oncologists reported in general good knowledge and few perceived limitations and barriers for pain management. However, multi-disciplinary management and collaboration with other specialists are still uncommon. Oncologists’ commitment to optimize pain management seems important to improve and maintain good practices

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A survey of perceptions, attitudes, knowledge and practices of medical oncologists about cancer pain management in Spain.

PURPOSE: To monitor oncologists' perspective on cancer pain management. METHODS: An anonymized survey was conducted in two waves. First, over a convenience sample of oncologists known to be particularly concerned with the management of pain. Second, using a random sample of oncologists. RESULTS: In total, 73 and 82 oncologists participated in the first and second wave, respectively. Many oncologists reported to have good knowledge of analgesic drugs (95.9%), the mechanism of action of opioids (79.5%), and good skills to manage opioid-related bowel dysfunction (76.7%). Appropriate adjustment of background medication to manage breakthrough pain was reported by 95.5% of oncologists. Additionally, 87.7% (68.3% in the second wave, p = 0.035) of oncologists reported suitable opioid titration practices, and 90.4% reported to use co-adjuvant medications for neuropathic pain confidently. On the other hand, just 9.6% of oncologists participated in multidisciplinary pain management teams, and merely 30.3 and 27.1% reported to routinely collaborate with the Pain Clinics or involve other staff, respectively. Only 26.4% of the oncologists of the second wave gave priority to pain pathophysiology to decide therapies, and up to 75.6% reported difficulties in treating neuropathic pain. Significantly less oncologists of the second wave (82.9 vs. 94.5%, p = 0.001) used opioid rotation routinely. CONCLUSIONS: Unlike in previous surveys, medical oncologists reported in general good knowledge and few perceived limitations and barriers for pain management. However, multi-disciplinary management and collaboration with other specialists are still uncommon. Oncologists' commitment to optimize pain management seems important to improve and maintain good practices.

Naloxegol to Treat Constipation in a Patient Taking Opioids for Cancer Pain: A Case Report.

Opioid-induced constipation (OIC) is a common gastrointestinal adverse effect of opioids, which can severely affect compliance and adherence to pain medication regimens and quality of life. Naloxegol has demonstrated efficacy against OIC in several studies involving patients with nonmalignant chronic pain. Here we report efficacy and tolerability of naloxegol in a 68-year-old patient with metastatic lung cancer and severe pain, treated with opioids, who presented with OIC resistant to traditional measures. Addition of naloxegol produced rapid improvement in his OIC symptoms and no apparent adverse effects while taking extended-release morphine 130 mg orally every 12 hours.

Capsaicin 8% Patch Repeat Treatment in Nondiabetic Peripheral Neuropathic Pain: A 52-Week, Open-Label, Single-Arm, Safety Study.

OBJECTIVES: To investigate the long-term safety and tolerability of capsaicin 8% patch repeat treatment in nondiabetic patients with peripheral neuropathic pain. METHODS: A prospective, open-label, observational study in patients with postherpetic neuralgia, posttraumatic or postsurgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral neuropathic pain, and average daily pain score ≥4, who received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9 to 12 wk intervals). Sensory testing and analgesic effectiveness were assessed using "bedside tests" and Brief Pain Inventory (question 5). RESULTS: Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least 2 sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least 1 modality in 50.4% (n=140); deterioration/loss in 1, 2, 3, 4, or 5 modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7), and 1.4% (n=4) cases. Newly emergent hyperesthesia or allodynia was apparent in 1.1% to 3.6% of the cases (depending on modality) by EoS. Between 25.2% and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and month 12. CONCLUSIONS: Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.

Prevalencia y severidad de la disfunción intestinal inducida por opioides / Observational and cross-sectional study of prevalence and severity of the opioid-induced bowel dysfunction

OBJETIVO: Analizar la prevalencia y severidad de los síntomas de disfunción intestinal inducida por opioides (DIO). DISEÑO: Estudio epidemiológico, observacional y transversal. Emplazamiento: Seis hospitales españoles. Participantes: Trescientos diecisiete pacientes en régimen ambulatorio con diagnóstico de dolor oncológico o dolor crónico no oncológico tratados con un único opioide mayor. Mediciones principales: La prevalencia de los síntomas de DIO y su severidad se midió usando una escala visual analógica (EVA: 0-100) y el estreñimiento se valoró también mediante el índice de función intestinal (BFI). Se registró el tratamiento para los síntomas gastrointestinales y se comparó su frecuencia según el tratamiento opioide. Finalmente, se estudió la calidad de vida. RESULTADOS: La tasa de prevalencia de al menos un trastorno gastrointestinal potencialmente relacionado con la DIO fue del 94,6%, siendo el estreñimiento el síntoma más frecuente (BFI: 91,6%; EVA: 90,2%) y casi la mitad de los pacientes (49,8%) presentaron 3 o más síntomas con un EVA ≥ 4. No se detectaron diferencias significativas en la prevalencia de los síntomas entre los distintos tratamientos opioides. Se detectó una afectación en la calidad de vida de los pacientes relacionada con la presencia de síntomas gastrointestinales de moderada a severa. CONCLUSIONES: En pacientes con tratamiento opioide se constata una elevada frecuencia de trastornos gastrointestinales posiblemente relacionados con la DIO, lo que subraya la necesidad de nuevas estrategias para su tratamiento (AU)

OBJECTIVE: To analyze the prevalence and severity of the opioid-induced bowel dysfunction(OBD) symptoms. DESIGN: Epidemiological, observational and cross-sectional study. Location: Six Spanish centers participated. Participants: A total of 317 outpatients with a diagnosis of cancer pain or non-cancer pain treated with a unique opioid were recruited. Main measurements: The prevalence of OBD symptoms was measured using a visual analog scale (VAS: 0-100), and constipation was also assessed by the Bowel Function Index (BFI). The treatment for gastrointestinal symptoms was recorded, and the frequency of symptoms between different opioid treatments was compared. Finally, quality of life was evaluated. RESULTS: The prevalence of OBD with at least one gastrointestinal disorder was 94.6%, with constipation being the most frequent symptom (BFI: 91.6%; VAS: 90.2%) and nearly half of the patients showed three or more symptoms with a VAS≥4. No significant differences were detected in the prevalence of symptoms between the opioid groups. A decrease in the wellbeing of patients was detected related to moderate to severe gastrointestinal symptoms. CONCLUSIONS: A high rate of gastrointestinal disorders probably related to OBD have been confirmed in patients on opioid therapy, highlighting the need for new drug strategies (AU)

[Observational and cross-sectional study of prevalence and severity of the opioid-induced bowel dysfunction]. / Prevalencia y severidad de la disfunción intestinal inducida por opioides.

OBJECTIVE: To analyze the prevalence and severity of the opioid-induced bowel dysfunction (OBD) symptoms. DESIGN: Epidemiological, observational and cross-sectional study. LOCATION: Six Spanish centers participated. PARTICIPANTS: A total of 317 outpatients with a diagnosis of cancer pain or non-cancer pain treated with a unique opioid were recruited. MAIN MEASUREMENTS: The prevalence of OBD symptoms was measured using a visual analog scale (VAS: 0-100), and constipation was also assessed by the Bowel Function Index (BFI). The treatment for gastrointestinal symptoms was recorded, and the frequency of symptoms between different opioid treatments was compared. Finally, quality of life was evaluated. RESULTS: The prevalence of OBD with at least one gastrointestinal disorder was 94.6%, with constipation being the most frequent symptom (BFI: 91.6%; VAS: 90.2%) and nearly half of the patients showed three or more symptoms with a VAS ≥ 4. No significant differences were detected in the prevalence of symptoms between the opioid groups. A decrease in the wellbeing of patients was detected related to moderate to severe gastrointestinal symptoms. CONCLUSIONS: A high rate of gastrointestinal disorders probably related to OBD have been confirmed in patients on opioid therapy, highlighting the need for new drug strategies.

Tapentadol prolonged release versus strong opioids for severe, chronic low back pain: results of an open-label, phase 3b study.

INTRODUCTION: This open-label, phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release (PR; 50-250 mg twice daily [b.i.d.]) for managing severe, chronic low back pain in patients responding to World Health Organization (WHO) step III opioids but tolerating treatment poorly. Equianalgesic ratios for tapentadol to prior strong opioids were calculated. METHODS: Patients rotated directly from prior WHO step III opioids to tapentadol. Patients received tapentadol PR (50-250 mg b.i.d.) during 5-week titration and 7-week maintenance periods. Tapentadol immediate release (IR) 50 mg (≤ twice/day, ≥ 4 h apart) was allowed (total daily dose of tapentadol PR and IR ≤ 500 mg/day). The primary endpoint was responder rate 1 at week 6 (percentage of patients with the same or less pain intensity [11-point numerical rating scale (NRS; 3-day average)] vs week -1). RESULTS: Responder rate 1 at week 6 (last observation carried forward [LOCF]) was 80.9% (76/94; P < 0.0001 vs. the null responder hypothesis rate [<60%]), resulting in a positive trial despite premature termination (136 recruited of 180 planned). Significant improvements from baseline in pain intensity and neuropathic pain symptoms were observed at weeks 6 and 12 with tapentadol PR (P < 0.05). Equianalgesic ratios were calculated for PR formulations alone and for PR and IR formulations combined for tapentadol to oxycodone, buprenorphine, fentanyl, morphine, and hydromorphone. The prevalences of adverse events reported as the reason for switching to tapentadol (most commonly constipation and nausea) decreased over time. CONCLUSIONS: Tapentadol PR (50-250 mg b.i.d.) provided at least comparable pain relief and improved tolerability versus prior strong opioids in patients with severe, chronic low back pain responding to WHO step III therapy. Conversion from strong opioids to tapentadol PR, with its two mechanisms of action, went smoothly considering overall effectiveness and tolerability outcomes. Equianalgesic ratios of tapentadol to oxycodone and other strong opioids were in line with other phase 3/3b studies.

Breakthrough cancer pain - still a challenge.

Breakthrough cancer pain is defined as transient pain exacerbation in patients with stable and controlled basal pain. Although variable, the prevalence of breakthrough cancer pain is high (33%-95%). According to the American Pain Foundation, breakthrough pain is observed in 50%-90% of all hospitalized cancer patients, in 89% of all patients admitted to homes for the elderly and terminal-patient care centers, and in 35% of all ambulatory care cancer patients. The management of breakthrough cancer pain should involve an interdisciplinary and multimodal approach. The introduction of new fentanyl formulations has represented a great advance and has notably improved treatment. Among these, the pectin-based intranasal formulation adjusts very well to the profile of breakthrough pain attacks, is effective, has a good toxicity profile, and allows for convenient dosing - affording rapid and effective analgesia with the added advantage of being easily administered by caregivers when patients are unable to collaborate.

Cost-effectiveness of tapentadol in severe chronic pain in Spain: a cost analysis of data from RCTs.

BACKGROUND: Chronic pain is known to be a significant and common health problem. Tapentadol, a recently developed centrally active, oral analgesic agent is used to treat adults with severe chronic pain that can be adequately managed only with opioid analgesics. Tapentadol has been reported to provide an improved adverse-events (AE) profile compared with other potent opioid analgesics at similar levels of analgesia. OBJECTIVES: The aim of this study was to compare the cost-effectiveness of tapentadol to that of opioids commonly used as first-line treatment of severe, chronic, nonmalignant pain from the perspective of the health care payer in Spain. METHODS: A Markov state-transition model was developed to compare the cost-effectiveness of first-line treatment with tapentadol to that of oxycodone, morphine, and transdermal fentanyl (TDF) over a 1-year time horizon. Four health states were defined: (1) treatment discontinuation due to a severe AE; (2) treatment discontinuation due to a lack of efficacy; (3) occurrence of an AE that required medical treatment; and (4) no discontinuation and no AE. If a patient discontinued a treatment, he or she was switched to an alternative, second-line opioid. Data regarding efficacy, tolerability, and utility values (EQ-5D) were derived from randomized clinical trials. Clinical experts estimated the rates of switching to other opioids and the health care resource utilization associated with the treatment of severe chronic pain. Unit costs were derived from public price lists/tariff works and were calculated from the perspective of the National Spanish Health System. The robustness of the model results was tested in extensive sensitivity analyses in which event probabilities, costs, utilities, and treatment-switching rates were altered. RESULTS: Data from 3 studies (1981 patients) were included in the model. Overall, the model predicted that initiating first-line treatment with tapentadol in patients with severe, chronic, nonmalignant pain was associated with lower costs and greater efficacy versus first-line treatment with oxycodone. Compared with morphine and TDF, tapentadol yielded incremental cost-effectiveness ratios of €2656 and €2069 per quality-adjusted life-year gained, respectively. On extensive 1-way and scenario analyses, findings on the cost-effectiveness of tapentadol were consistent. The probability that tapentadol would be cost-effective compared with each comparator at the willingness-to-pay threshold of €20,000 to €30,000/QALY gained exceeded 90%. CONCLUSIONS: Based on the findings from the present model, tapentadol is likely to be a cost-effective first-line treatment in patients with severe, chronic, nonmalignant pain in Spain according to the commonly accepted willingness-to-pay thresholds. Compared with morphine and TDF, the incremental cost-effectiveness ratios were low; compared with oxycodone, tapentadol dominated, showing better quality-of-life outcomes at lower costs.

Is morphine still the best reference opioid?

SUMMARY Cancer and noncancer pain can usually be managed according to the WHO analgesic ladder and, in many countries, morphine remains the first-line opioid of choice for chronic severe pain. There have been many advances in the use of opioids for moderate-to-severe pain control in recent years. Consequently, the position of morphine as the gold standard became gradually more questioned, mostly because of serious adverse effects and the availability of different opioids and new formulations. The place of morphine as the first-line option is based on reasons of familiarity, availability or cost rather than medical advantages. In recent years, a number of systematic reviews failed to demonstrate superiority of morphine over other opioids in terms of efficacy or tolerability. Moreover, some strong opioids have shown improved tolerability or convenience. Currently, morphine might still be considered as a reference drug for equivalent dosing, but not for strategic healthcare decisions, as it has not demonstrated clinical or pharmacological superiority over other opioids. Therefore, there is a lack of evidence to sustain the role of morphine as the gold standard in the treatment of chronic severe pain.

Efficacy and safety of fentanyl pectin nasal spray compared with immediate-release morphine sulfate tablets in the treatment of breakthrough cancer pain: a multicenter, randomized, controlled, double-blind, double-dummy multiple-crossover study.

BACKGROUND: Immediate-release morphine sulfate (IRMS) remains the standard treatment for breakthrough cancer pain (BTCP), but its onset of effect does not match the rapid onset and short duration of most BTCP episodes. OBJECTIVE: This study will evaluate the efficacy/tolerability of fentanyl pectin nasal spray (FPNS) compared with IRMS for BTCP. METHODS: Patients (n = 110) experiencing one to four BTCP episodes/day while taking ≥ 60 mg/day oral morphine (or equivalent) for background cancer pain entered a double-blind, double-dummy (DB/DD), multiple-crossover study. Patients completing a titration phase (n = 84) continued to a DB/DD phase: 10 episodes of BTCP were randomly treated with FPNS and oral capsule placebo (five episodes) or IRMS and nasal spray placebo (5 episodes). The primary end point was pain intensity (P < .05 FPNS vs. IRMS) difference from baseline at 15 minutes (PID(15)). Secondary end points were onset of pain intensity (PI) decrease (≥ 1-point) and time to clinically meaningful pain relief (CMPR, ≥ 2-point PI decrease). Safety and tolerability were evaluated by adverse events (AEs) and nasal assessments. By-patient and by-episode analyses were completed. RESULTS: Compared with IRMS, FPNS significantly improved mean PID(15) scores. 57.5% of FPNS-treated episodes significantly demonstrated onset of PI improvement by 5 minutes and 95.7% by 30 minutes. CMPR (≥ 2-point PI decrease) was seen in 52.4% of episodes by 10 minutes. Only 4.7% of patients withdrew from titration (2.4% in DB/DD phase) because of AEs; no significant nasal effects were reported. CONCLUSION: FPNS was efficacious and well tolerated in the treatment of BTCP and provided faster onset of analgesia and attainment of CMPR than IRMS.

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.