Serge Perrot’s research while affiliated with Université Paris Cité and other places

High-concentration capsaicin patch (HC capsaicin patch) is a locally acting treatment option for adults with peripheral neuropathic pain (pNeP) of various etiologies. Numerous clinical trials, post hoc analyses, and meta-analyses have investigated the efficacy and tolerability of the HC capsaicin patch. Despite this extensive body of research, a comprehensive narrative review covering publications on different pNeP conditions is lacking. This narrative review aims to fill the gap by analyzing 52 studies, including randomized controlled trials and real-world evidence. The results show that the HC capsaicin patch consistently provides pain relief and improves quality of life for several pNeP conditions, with increasing benefits seen with repeated treatments. It was found to be superior to placebo and comparable to standard care, regardless of the origin of the pain. Early initiation of therapy appears to improve efficacy, although patients with more prolonged pain also benefit. While the exact mechanisms of action are still unclear, there is evidence to suggest a potential benefit from nerve regeneration in some conditions. However, limited information exists regarding the alteration of treatment intervals and the variation in the size of the painful area upon re-treatment. The review also identifies variability in response rates for different types of pNeP and a lack of reliable predictors of treatment success, indicating a need for further research. In conclusion, the HC capsaicin patch is effective and well tolerated across a range of pNeP conditions, with increasing efficacy upon retreatment. It is a valuable treatment option, although more research is needed to refine its clinical use and explore its full therapeutic potential.

Objective In rheumatoid arthritis (RA) and spondyloarthritis (SpA), managing persistent pain remains challenging. Little is known regarding impaired pain pathways in these patients and the impact of biologic disease‐modifying antirheumatic drugs (bDMARDs). The objective of the Rheumatism Pain Inhibitory Descending Pathways study was to assess pain thresholds and descending pain modulation in patients with active RA or SpA following introduction of a tumor necrosis factor inhibitor (TNFi). Methods Patients with active disease (50 with RA and 50 with SpA) naive to bDMARDs or targeted synthetic DMARDs and starting a TNFi were included. Patients were observed for six months after TNFi initiation with clinical, psychological, and pain assessment. At all visits, participants underwent quantitative sensory testing with heat and cold pain thresholds and descending inhibition by conditioned pain modulation (CPM). Descending pain control (CPM effect) was assessed as the change in heat pain threshold (°C) following a conditioning stimulus. Results Of the 100 patients (59 women, mean ± SD age 45.8 ± 14.6 years), 74 completed the six‐month follow‐up. Thermal pain thresholds did not significantly change during follow‐up. CPM effect improved significantly during follow‐up (mean ± SD 0.25 ±2.57°C at baseline and 2.96 ± 2.50°C at six months; P < 0.001). At the end of follow‐up, the mean CPM effect was significantly higher in patients without significant pain compared with patients with persistent pain (>3 of 10 on the Brief Pain Inventory) (mean ± SD 3.25 ± 2.68°C vs 2.47 ± 2.11°C; P = 0.04) and in patients achieving remission or low disease activity compared with patients with active rheumatism (mean ± SD 3.31 ± 2.68°C vs 2.18 ± 1.87°C; P = 0.01). Conclusion In active inflammatory rheumatisms, impaired descending pain modulation, but not thermal pain thresholds, is improved after TNFi treatment, suggesting a possible effect of TNFi on central pain modulation.

Pharmacological approaches are frequently proposed in fibromyalgia, based on different rationale. Some treatments are proposed to alleviate symptoms, mainly pain, fatigue, and sleep disorder. Other treatments are proposed according to pathophysiological mechanisms, especially central sensitization and abnormal pain modulation. Globally, pharmacological approaches are weakly effective but market authorization differs between Europe and United States. Food and Drug Administration–approved medications for fibromyalgia treatment include serotonin and noradrenaline reuptake inhibitors, such as duloxetine, and pregabalin (an anticonvulsant), which target neurotransmitter modulation and central sensitization. Effect of analgesics, especially tramadol, on pain is weak, mainly on short term. Low-dose naltrexone and ketamine are gaining attention due their action on neuroinflammation and depression modulation, but treatment protocols have not been validated. Moreover, some treatments should be avoided due to the high risk of abuse and severe side effects, especially opioids, steroids, and hormonal replacement.

Objectives To summarise and evaluate Cochrane reviews of pharmacological therapies for adults with fibromyalgia syndrome (FMS) pain. Methods Systematic search of Cochrane Database of Systematic Reviews to May 2024. Generic quality assessment used AMSTAR-2 criteria, validity checks of potentially critical factors in evaluation of analgesic efficacy, and assessment of susceptibility of results to publication bias. Pain outcomes were participant-reported pain relief of ≥ 30% or ≥ 50%, or PGIC much or very much improved. Results Twenty-one reviews (87 trials, 17,631 patients) were included. All rated moderate (15) or high-quality (6) using AMSTAR-2 and at least seven of eight critical pain criteria were met by 13 of 21 reviews. Diagnosis of FMS used recognised criteria. Seven reviews found no trials (carbamazepine, clonazepam, lamotrigine, phenytoin, oxycodone, topiramate, or valproate), seven had limited and inadequate data (antipsychotics, cannabinoids, combination therapy, gabapentin, lacosamide, monoamine oxidase inhibitors, NSAIDs), and two were subject to publication bias (amitriptyline, SSRI). Mirtazapine had moderate evidence of no effect. Duloxetine, milnacipran, and pregabalin had moderate/good evidence of substantial pain relief for 4-12 weeks in around 1 in 10 adults with moderate or severe FMS pain, without evidence of efficacy beyond six months. Serious adverse events were no more common than with placebo. There was no evidence about who might benefit or experience adverse events. There was no substantial efficacy evidence for other medicines. Conclusions Duloxetine, milnacipran, and pregabalin had good evidence that about 1 person in 10 with moderate or severe pain experienced pain intensity reduction by at least 50%.

Objectives To summarise and evaluate Cochrane reviews of pharmacological therapies for adults with fibromyalgia syndrome (FMS) pain. Methods Systematic search of Cochrane Database of Systematic Reviews to May 2024. Generic quality assessment used AMSTAR-2 criteria, validity checks of potentially critical factors in evaluation of analgesic efficacy, and assessment of susceptibility of results to publication bias. Pain outcomes were participant-reported pain relief of ≥ 30% or ≥ 50%, or PGIC much or very much improved. Results Twenty-one reviews (87 trials, 17,631 patients) were included. All rated moderate (15) or high-quality (6) using AMSTAR-2 and at least seven of eight critical pain criteria were met by 13 of 21 reviews. Diagnosis of FMS used recognised criteria. Seven reviews found no trials (carbamazepine, clonazepam, lamotrigine, phenytoin, oxycodone, topiramate, or valproate), seven had limited and inadequate data (antipsychotics, cannabinoids, combination therapy, gabapentin, lacosamide, monoamine oxidase inhibitors, NSAIDs), and two were subject to publication bias (amitriptyline, SSRI). Mirtazapine had moderate evidence of no effect. Duloxetine, milnacipran, and pregabalin had moderate/good evidence of substantial pain relief for 4-12 weeks in around 1 in 10 adults with moderate or severe FMS pain, without evidence of efficacy beyond six months. Serious adverse events were no more common than with placebo. There was no evidence about who might benefit or experience adverse events. There was no substantial efficacy evidence for other medicines. Conclusions Duloxetine, milnacipran, and pregabalin had good evidence that about 1 person in 10 with moderate or severe pain experienced pain intensity reduction by at least 50%.

Objective Neuroimaging investigations are critical to provide a more direct assessment of brain disturbances associated with osteoarthritis (OA)-related pain, and to better understand its pathophysiology to develop new treatment strategies. This viewpoint aims to summarize the importance of the brain in OA pain. Method A European working group on pain in osteoarthritis GO-PAIN (Going Inside Osteoarthritis-related Pain Phenotyping) has been created to work on a global assessment of the OA-related pain. Relevant scientific literature was evaluated, summarized and discussed to expose advances in functional brain alterations related-to OA pain. Results Findings of neuroimaging studies are highly heterogenous and based on small sample size, but some key brain alterations associated with OA pain can be identified across experiments. A systematic literature review conducted by Hall and colleagues (2023) found lower activity, connectivity, and grey matter volume in the right anterior insula in patients with OA than in healthy controls. Other works also pointed out that activity of specific brain regions could serve as a potential surrogate biomarker, but several limitations and confounding factors needs to be addressed. Conclusions Brain functional imaging provides opportunities to accurately address an OA-related pain endophenotype. To encompass limitations and fill the gaps from the previous studies, we propose a blueprint for the next 5 years and stimulate ideas for others working in the field.

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.

Introduction: Dexketoprofen/tramadol 25/75 mg (DKP/TRAM) is a fixed-dose combination of a cyclooxygenase inhibitor and opioid receptor agonist. To better understand the efficacy and safety of DKP/TRAM in the treatment of moderate to severe acute lower back pain (LBP) with or without radiculopathy, we carried out a large explorative phase IV international, multicenter, prospective, randomized, double-blind, parallel group, placebo-controlled study (DANTE). Methods: A total of 538 patients with or without a history of LBP and experiencing acute LPB of moderate to severe intensity [Numerical Rating Scale-Pain Intensity (NRS-PI) score > 5] were randomized 4:4:1:1 to DKP/TRAM 25/75 mg every 8 h (n = 211), tramadol (TRAM) 100 mg (n = 207), placebo-matched DKP/TRAM (n = 59), or placebo-matched TRAM (n = 61). Results: The proportion of patients achieving the primary endpoint, defined as the time to first achieve NRS-PI score < 4 or pain intensity reduction ≥ 30% from drug intake up to 8 h after the first dose, was higher in the DKP/TRAM arm than in the placebo group, but the difference was not statistically significant (46.1% vs. 42.6%, respectively; hazard ratio 1.11; 95% confidence interval 0.775, 1.595; p = 0.566). DKP/ TRAM achieved superiority over TRAM in total pain relief at 4, 6, and 8 h (p < 0.05). Conversely, in relation to the secondary endpoints, a significantly greater reduction in NRS-PI score was seen with DKP/TRAM versus placebo starting from 1 h, and this reduction remained numerically lower throughout 8 h. Summed pain intensity difference values were also significantly lower at 4, 6, and 8 h with DKP/TRAM compared to TRAM (p < 0.05). Overall, DKP/TRAM was well tolerated. Conclusion: Although the primary endpoint was not met, secondary efficacy analyses suggest the superiority of DKP/TRAM over placebo and TRAM alone in terms of total pain relief. DKP/TRAM can be considered to be an effective and safe option for the treatment of moderate to severe acute LBP.