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Background: Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in low-income regions including Africa. This study aimed to provide updated and comprehensive data on changes in opioid consumption, specifically in Africa., Methods: This longitudinal study has updated and expanded upon the International Narcotics Control Board data obtained from 1999 to 2021, assessing opioid consumption trends across all African countries. The defined daily doses for statistical purposes (SDDD) was used to determine the changes in opioid consumption in Africa. In addition, we used sub-analyses of the data to delve into individual substances, income levels, cancer incidence, cancer mortality, and sub-regional cluster analysis (based on the language spoken) to identify possible disparities and inform further research and tailored solutions., Findings: Our results indicate a persistently low and stagnant trend in opioid consumption between 2001-03 and 2019-21, from 73 SDDD (95% CI 69-77) to 55 SDDD (32-79). In-depth analysis revealed a morphine consumption increase from 735 SDDD in 1999 to 1115 SDDD in 2021. Moreover, opioid consumption was closely related to country-level income levels, with most of the low-income and lower-middle-income African countries reporting low opioid consumption. Notably, the escalating incidence and mortality rates associated with cancer in Africa indicated a misalignment with the trajectory of opioid use. Additionally, French-speaking African countries exhibited lower opioid usage than the rest of the continent, suggesting avenues for research into cultural, political, and social aspects., Interpretation: In the context of global doubling in opioid consumption, Africa has shown insufficient and stagnant opioid consumption during the last 20 years. These findings underscore the need for policy reform to facilitate safe and responsible opioid access in Africa, particularly for legitimate indications such as cancer pain and palliative care., Funding: None., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Abstract: Experimental studies have suggested that nitrous oxide-induced analgesia depends on interactions with opioids. On the basis of these results, we hypothesized that the effects of inhaled nitrous oxide/oxygen (N 2 O/O 2 ) 50%-50% equimolar mixture (EMONO) on patients with neuropathic pain would be higher in those receiving concomitant opioids. To test this hypothesis, we did exploratory post hoc analyses of our recently published ProtoTOP study to compare the effects of EMONO and placebo in patients with or without concomitant opioid treatment. A total of 92 patients of the 221 (ie, 41.6%) included in the ProtoTOP study were concomitantly treated with opioids. In contrast with our previous analyses, average pain intensity was significantly decreased in comparison with placebo one week after the last treatment administration in patients treated with opioids, but not in those treated without opioid, and this effect was maintained over the 4-week follow-up period. Neuropathic pain symptom inventory (NPSI total and subscores) was also significantly more decreased after inhalation of EMONO in comparison with placebo only in patients receiving opioids. The proportion of patients with at least 30% pain reduction and of those reporting an overall improvement with the Patient Global Impression of Change were significantly higher only in this population of patients. In conclusion, these results complement our previous analyses with the identification of a specific population of responders to EMONO inhalation in patients with neuropathic pain. As suggested by experimental studies, we hypothesized that these long-lasting analgesic effects could depend on the anti-N-methyl-D-aspartate properties of N 2 O., (Copyright © 2022 International Association for the Study of Pain.)

Objectives: Given the scope of rheumatology and its prevalence of pain, it seems needed that a study should focus on prescription habits, in the midst of the international opioid epidemic and given the moderate efficacy of strong opioids in chronic musculoskeletal conditions. We compared rheumatologists' opioid prescribing patterns in non-cancer pain with recommended practice., Methods: We performed a cross-sectional study of the French health insurance database, including all patients aged 16 years or over reimbursed for at least one strong opioid prescription from a rheumatologist in 2015. A nationwide survey of all registered rheumatologists in France was performed with a 47-item questionnaire in June 2015., Results: Only 2.4% of the patients receiving a strong opioid in 2015 (n=700,946) had at least one prescription from a rheumatologist. Rheumatologists prescribed mostly morphine, and significantly less oxycodone and fentanyl (P<0.00001) than other specialists. Rheumatologists prescribed a mean of 35.8mg morphine equivalent/day. A response rate of 33.7% was obtained to the questionnaire. Acute musculoskeletal pain was the principal condition for strong opioids prescription, with 94.5% re-evaluating opioid treatment within two weeks of initiation. For efficacy, 80% said that they stopped treatment if no benefit was observed after a test period (mean=1.2 months). Rheumatologists with pain management training were significantly more likely to evaluate pain before prescribing strong opioids (P=0.001), evaluate efficacy within three months (P=0.01) and screen for risk factors for misuse at initiation (P<0.0001)., Conclusions: For non-cancer pain, rheumatologists generally prescribe opioids for short periods, at low doses, mostly according to national recommendations. Pain education strongly affected opioid prescription by rheumatologists., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Prescription opioid use disorder (POUD) is an established public health crisis in many countries, and current evidence indicates it is a growing problem in Europe. Many specialists play a role, including pain and addiction medicine specialists, in the diagnosis and management of POUD, but neither group can fully address these patients' needs alone. The purpose of this consensus process was to bring together experts from pain and addiction medicine to examine the positions of both specialties., Methods: In all, 13 international pain medicine, addiction medicine, and addiction psychiatry experts convened a meeting to formulate a set of consensus statements on the diagnosis and management of POUD. The statements were further refined by a wider group of 22 European expert clinicians. At a second meeting of all 35 participants, a set of controversy statements was also developed to recognize some of the key areas of divergent opinion., Results/conclusions: There was a high level of agreement between pain and addiction specialists. Key themes that emerged were the need to strengthen interdisciplinary communication, a desire for greater education and training for clinicians in both specialties, and mutual acknowledgment of the importance of multidisciplinary management of POUD. The blurred line between poorly managed pain and POUD was also a subject of much discussion, reflecting the difficulties in defining and diagnosing this complex condition.

Introduction: In 2016, the orally administered fixed-dose combination of dexketoprofen 25 mg and tramadol 75 mg (DKP/TRAM FDC) was approved in Europe for short-term treatment of moderate-to-severe acute pain, an indication that encompasses a wide range of post-operative and non-surgical painful conditions. This has suggested the necessity to have a clearer indication on its clinical use, with the support of expert pain clinicians, working in different medical specialities, and reinforced by the data present in the literature., Methods: With the aim of assisting clinicians in the use of DKP/TRAM FDC in daily practice, two rounds of a modified Delphi process were conducted. In the first round, a board of nine experts developed a series of consensus statements based on available evidence, and their clinical experience, with DKP/TRAM FDC. In the second round, 75 clinicians with extensive experience in pain management expressed individually their agreement with the statements, using a dedicated online platform. Consensus was defined as at least 70% agreement., Results: Twenty-eight statements were developed. Of these, 19 reached the defined level of consensus., Conclusion: The agreed consensus statements may assist clinicians in applying the results of clinical studies and clinical experience to routine care settings, providing guidance for use of this new analgesic combination in moderate-to-severe post-operative and non-surgical acute pain., Funding: Menarini Group.

An endemic increase in the number of deaths attributable to prescribed opioids is found in all developed countries. In 2016 in the USA, more than 46 people died each day from overdoses involving prescription opioids. European data show that the number of patients receiving strong opioids is increasing. In addition, there is an upsurge in hospitalisations for opioid intoxication, opioid abuse and deaths in some European countries. This class of analgesic is increasingly used in many rheumatological pathologies. Cohort studies, in various chronic non-cancer pain (CNCP) (osteoarthritis, chronic low back pain, rheumatoid arthritis, etc), show that between 2% and 8% of patients are treated with strong opioids. In order to help rheumatologists prescribe strong opioids under optimal conditions and to prevent the risk of death, abuse and misuse, recommendations have recently been published (in France in 2016, the recommendations of the French Society of Study and Treatment of Pain, in 2017, the European recommendations of the European Federation of IASP Chapters and the American Society of International Pain Physicians). They agree on the same general principles: opioids may be of interest in situations of CNCP, but their prescription must follow essential rules. It is necessary to make an accurate assessment of the pain and its origin, to formulate therapeutic objectives (pain, function and/or quality of life), to evaluate beforehand the risk of abuse and to get a specialised opinion beyond a certain dose or duration of prescription., Competing Interests: Competing interests: A-PT reports personal fees from Pfizer, from Menarini and from Astellas, outside the submitted work; FB has received consulting fees or other remuneration from AbbVie, Merck, Regulaxis, 4P Pharma, Bone Therapeutics, Galapagos, Peptinov, Expanscience, Flexion, Janssen, Merck Serono, Novartis, Roche, Gilead, Sanofi, GSK, Boehringer, Sandoz, Eli Lilly and Company, Servier, TRB Chemedica, UCB, Pfizer, Nordic Pharma, and Regeneron; outside the submitted work SP reports grants from Grunenthal, personal fees from BMS UPSA, outside the submitted work.

Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone)., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background: Despite the development of multimodal analgesia for postoperative pain management, opioids are still required for effective pain relief after knee arthroplasty. We aimed to identify the determinants of post-operative pain intensity and post-operative opioid requirement in this context., Methods: In this observational prospective study, we recorded patient characteristics, pre-operative pain intensity, anxiety and depression levels, sensitivity and pain thresholds in response to an electrical stimulus, and mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms. Multivariate linear regression models were used to identify predictors of post-operative pain at rest and opioid requirement., Results: We included 109 patients. Pre-operative pain at rest (p = 0.047), anxiety level (p = 0.001) and neuropathic pain symptoms (p = 0.030) were independently and positively associated with mean post-operative pain intensity adjusted for mean post-operative morphine equivalent dose (MED). Mean post-operative pain intensity at rest was lower (p = 0.006) in patients receiving celecoxib and pregabalin in the post-operative period, with all other variables constant. Mean post-operative MED over 5 days was low, but highly variable (78.2 ± 32.1 mg, from 9.9 to 170 mg). Following adjustment for mean post-operative pain intensity, it was independently negatively correlated with age (p = 0.004), and positively correlated with associated paracetamol treatment (p = 0.031). No genetic effect was detected in our sample., Conclusions: Our findings suggest that clinicians could use the pre-operative pain profile, in terms of anxiety levels, neuropathic pain symptoms, and chronic pre-operative pain intensity, to improve the efficacy of pain management after knee surgery., (© 2015 European Pain Federation - EFIC®)

Rationale, Aims and Objectives: The objective was to compare the extent of pain interference and pain medication among persons who were classified as obese [body mass index (BMI)≥ 30 kg m(-2) ] and normal weighted (BMI  ≤ 25 kg m(-2) ), before a hip or knee replacement surgery., Methods: Patients candidate for an orthopaedic surgery were successively enrolled, over a 6-month period, and classified in either the normal weight (BMI  ≤ 25 kg m(-2) ) or the obese (BMI ≥ 30 kg m(-2) ) categories. Data were collected using self-administered questionnaires with items concerning pain characteristics, pain medication and pain interference. Two standardized questionnaires were associated: the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression scale (HAD)., Results: Fifty-two obese patients (candidates for 24 hip replacements and 28 knee replacements) and 51 non-obese (23 hip replacements and 28 knee replacements) were enrolled. Obese patients suffered from a higher rate of acute pain episodes than non-obese patients (65 versus 44%, P<0.05). Pain interference on walking distance, sleep and relations with others was higher in obese patients. HAD score showed no significant difference between groups. The use of strong opioids and of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly more important in obese patients (13 versus 0% and 31 versus 14%)., Conclusions: Obese patients suffer more significantly of unrelieved chronic pain, which lowers considerably their quality of life. Pain relief is more difficult to obtain, as it requires stronger pain medication and NSAIDs., (© 2014 John Wiley & Sons, Ltd.)

Objective: To describe the prevalence of opioid-induced constipation (OIC) in patients with cancer pain according to the Knowles-Eccersley-Scott symptom score (KESS), the different symptoms of opioid-induced bowel dysfunction (OIBD), and to assess the impact of OIBD on patient's quality-of-life., Methods: A cross-sectional observational study, using the KESS questionnaire and the physician's subjective assessment of constipation, and other questionnaires and questions on constipation, OIBD, and quality-of-life, carried out on 1 day at oncology day centres and hospitals., Results: Five hundred and twenty patients were enrolled at 77 centres in France; 61.7% of patients (n = 321) showed a degree of constipation that is problematic for the patient according to KESS (between 9-39). Even more patients, 85.7% (n = 438), were considered constipated according to the physician's subjective assessment-despite laxative use (84.7% of patients). Quality-of-life was significantly reduced in constipated vs non-constipated patients for both PAC-QoL (p < 0.0001 for total score and each dimension) and the SF-12 questionnaires (statistically significant for all dimensions except physical state and role physical). OIC and OIBD led to hospitalization (16% of patients), pain (75% of patients), and frequent changes in opioid and laxative treatment., Key Limitations: This cross-sectional study, in a selected population of cancer patients, has measured prevalence and impact of OIBD. Further confirmation could be sought through the use of longitudinal studies, and larger populations, such as non-cancer pain patients treated with opioids., Conclusions: Cancer patients taking opioids for pain are very frequently constipated, even if they are prescribed laxatives. This leads to relevant impairments of quality-of-life.

An increasing number of obese patients are undergoing surgery, particularly bariatric and orthopaedic surgery. The physiological differences between obese and normal-weight subjects may modify not only anaesthetic requirements during surgery but also post-operative analgesic management, raising a number of challenges in a critical period. In this review, we analyse studies of post-operative pain management with opioids in obese subjects. We discuss the genetic factors common to pain and obesity and the factors potentially modifying opioid pharmacokinetics and pharmacodynamics in obese patients, and we analyse the overall efficacy and safety of opioids for pain management during the post-operative period in obese patients. Both modifications to surgical methods and additional analgesic treatments to decrease the requirement for opioids may improve early rehabilitation and quality of care and reduce adverse effects in obese patients.

Chronic pain has a growing incidence with age. In the elderly, the most frequent etiologies of pain are musculoskeletal diseases, neuropathic pain and cancer. Pain management in older patients requires a comprehensive assessment, adapted to the patient's cognitive functioning, using specific tools, and taking into account the daily life activities and autonomy. Management includes drugs, especially paracetamol and level 2 and 3 opioids. Non steroidal anti-inflammatory drugs (NSAIDs) should be avoided, including COX-2 inhibitors. Drugs are to be prescribed regularly, pre-emptively, and via oral route. Immediate release drugs should be selected, and a slow increase of dosages. Local treatments should be preferred: local injections, topical application and physiotherapy. Rehabilitation, pool-therapy, crenotherapy may be proposed. In conclusion, chronic pain management in elderly patients does not importantly differ from that in younger patients. Specificities are more related to the assessment of pain and to the drugs side effects rather than to the type of drugs.

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.

1. The management of chronic pain should be directed by the underlying cause of the pain. Whatever the cause, the primary goal of patient care should be symptom control. 2. Opioid treatment should be considered for both continuous neuropathic and nociceptive pain if other reasonable therapies fail to provide adequate analgesia within a reasonable timeframe. 3. The aim of opioid treatment is to relieve pain and improve the patient's quality of life. Both of these should be assessed during a trial period. 4. The prescribing physician should be familiar with the patient's psychosocial status. 5. The use of sustained-release opioids administered at regular intervals is recommended. 6. Treatment should be monitored. 7. A contract setting out the patient's rights and responsibilities may help to emphasize the importance of patient involvement. 8. Opioid treatment should not be considered a lifelong treatment., (2002 European Federation of Chapters of the International Association for the Study of Pain)

Background: It has been reported that opioid antinociceptive effects are enhanced in animal models of inflammation, but it remains unclear whether this sensitization to morphine is related to predominant central or peripheral increased effects., Methods: The authors compared the behavioral effects of intraplantar and intravenous morphine and naloxone in a rat model of repeated acute carrageenan-induced inflammation in which enhanced responses to noxious stimuli result from sensitization in peripheral tissues or central sensitization. The antinociceptive effects of intraplantar morphine (50, 75, 100, 150, and 200 microg), intravenous morphine (0.3, 0.6, and 1 mg/kg), and the pronociceptive effects of intraplantar naloxone methiodide (150 microg) and intravenous naloxone (1 mg/kg) against noxious pressure (vocalization thresholds to paw pressure) in rats were assessed 3 h after one or two carrageenan plantar injections performed 7 days apart., Results: After the first carrageenan injection, intraplantar and intravenous morphine produced significant increase of vocalization thresholds to paw pressure in inflamed but not in noninflamed paws. After the second carrageenan injection, the antinociceptive effects of intraplantar morphine were significantly reduced compared with those obtained after the first carrageenan injection, whereas effects of intravenous morphine were significantly enhanced and present in both hind paws. Intravenous naloxone demonstrated similar pronociceptive patterns after the first and second carrageenan injection. Intraplantar naloxone methiodide produced pronociceptive effects in inflamed hind paw that were significantly enhanced after the second carrageenan injection., Conclusions: When inflammation is enhanced by recurrent stimulations, the antinociceptive effects of systemic morphine are enhanced. This increase is more likely related to central than peripheral sites of action, beyond endogenous opioid system activation.