Recent advances in the understanding and management of chronic pancreatitis pain.

Abdominal pain is the most common symptom of chronic pancreatitis (CP) and is often debilitating for patients and very difficult to treat. To date, there exists no cure for the disease. Treatment strategies focus on symptom management and on mitigation of disease progression by reducing toxin exposure and avoiding recurrent inflammatory events. Traditional treatment protocols start with medical management followed by consideration of procedural or surgical intervention on selected patients with severe and persistent pain. The incorporation of adjuvant therapies to treat comorbidities including psychiatric disorders, exocrine pancreatic insufficiency, mineral bone disease, frailty, and malnutrition, are in its early stages. Recent clinical studies and animal models have been designed to improve investigation into the pathophysiology of CP pain, as well as to improve pain management. Despite the array of tools available, many therapeutic options for the management of CP pain provide incomplete relief. There still remains much to discover about the neural regulation of pancreas-related pain. In this review, we will discuss research from the last 5 years that has provided new insights into novel methods of pain phenotyping and the pathophysiology of CP pain. These discoveries have led to improvements in patient selection for optimization of outcomes for both medical and procedural management, and identification of potential future therapies.

Sensory phenotypes in complex regional pain syndrome and chronic low back pain-indication of common underlying pathomechanisms.

Introduction: First-line pain treatment is unsatisfactory in more than 50% of chronic pain patients, likely because of the heterogeneity of mechanisms underlying pain chronification. Objectives: This cross-sectional study aimed to better understand pathomechanisms across different chronic pain cohorts, regardless of their diagnoses, by identifying distinct sensory phenotypes through a cluster analysis. Methods: We recruited 81 chronic pain patients and 63 age-matched and sex-matched healthy controls (HC). Two distinct chronic pain cohorts were recruited, ie, complex regional pain syndrome (N = 20) and low back pain (N = 61). Quantitative sensory testing (QST) was performed in the most painful body area to investigate somatosensory changes related to clinical pain. Furthermore, QST was conducted in a pain-free area to identify remote sensory alterations, indicating more widespread changes in somatosensory processing. Results: Two clusters were identified based on the QST measures in the painful area, which did not represent the 2 distinct pain diagnoses but contained patients from both cohorts. Cluster 1 showed increased pain sensitivities in the painful and control area, indicating central sensitization as a potential pathomechanism. Cluster 2 showed a similar sensory profile as HC in both tested areas. Hence, either QST was not sensitive enough and more objective measures are needed to detect sensitization within the nociceptive neuraxis or cluster 2 may not have pain primarily because of sensitization, but other factors such as psychosocial ones are involved. Conclusion: These findings support the notion of shared pathomechanisms irrespective of the pain diagnosis. Conversely, different mechanisms might contribute to the pain of patients with the same diagnosis.

The Classification of Suspected Predominant Nociplastic Pain in People with Moderate and Severe Haemophilia: A Secondary Exploratory Study.

In people with haemophilia (PwH), joint pain is a major comorbidity that is often overlooked and under-treated. It is believed that, to ensure the most successful outcome, pain management should be tailored to the predominant pain phenotype (i.e., nociceptive, neuropathic and nociplastic). The 2021 clinical criteria and grading system for nociplastic pain, established by the International Association for the Study of Pain (IASP), emphasize the necessity of early-stage identification and predominant pain type classification. Consistent with findings in other chronic musculoskeletal pain conditions, studies suggest that a subgroup of PwH suffers from nociplastic pain, i.e., pain arising from altered nociception rather than structural damage, but this has not yet been explored in PwH. This study aimed to identify PwH with "unlikely", "possible" and "probable" nociplastic pain and investigate differences in anthropometric, demographic and clinical characteristics and psychological factors between subgroups of PwH and healthy individuals.: The IASP clinical criteria and grading system were used to classify pain types in adult men with moderate or severe haemophilia recruited from two Belgian haemophilia treatment centres. Statistical analyses were applied to study between-subgroup differences. Of 94 PwH, 80 PwH (85%) were classified with "unlikely" and 14 (15%) with "at least possible" nociplastic pain (including 5 PwH (5%) with "possible" and 9 PwH (10%) with "probable" nociplastic pain). PwH in both the "unlikely" and "at least possible" nociplastic pain groups showed significantly higher levels of unhelpful psychological factors compared to healthy individuals. Additionally, age may partially account for the observed differences in body height and psychological factors. Larger sample sizes may be needed to detect more subtle between-group differences. study confirmed the presence of nociplastic pain in haemophilia, categorising a notable subgroup as individuals who experience at least possible nociplastic pain. These exploratory insights may provide a starting point for future studies and the development of more effective and tailored pain management.

Dissecting central post-stroke pain: a controlled symptom-psychophysical characterization.

Central post-stroke pain affects up to 12% of stroke survivors and is notoriously refractory to treatment. However, stroke patients often suffer from other types of pain of non-neuropathic nature (musculoskeletal, inflammatory, complex regional) and no head-to-head comparison of their respective clinical and somatosensory profiles has been performed so far. We compared 39 patients with definite central neuropathic post-stroke pain with two matched control groups: 32 patients with exclusively non-neuropathic pain developed after stroke and 31 stroke patients not complaining of pain. Patients underwent deep phenotyping via a comprehensive assessment including clinical exam, questionnaires and quantitative sensory testing to dissect central post-stroke pain from chronic pain in general and stroke. While central post-stroke pain was mostly located in the face and limbs, non-neuropathic pain was predominantly axial and located in neck, shoulders and knees (P < 0.05). Neuropathic Pain Symptom Inventory clusters burning (82.1%, n = 32, P < 0.001), tingling (66.7%, n = 26, P < 0.001) and evoked by cold (64.1%, n = 25, P < 0.001) occurred more frequently in central post-stroke pain. Hyperpathia, thermal and mechanical allodynia also occurred more commonly in this group (P < 0.001), which also presented higher levels of deafferentation (P < 0.012) with more asymmetric cold and warm detection thresholds compared with controls. In particular, cold hypoesthesia (considered when the threshold of the affected side was <41% of the contralateral threshold) odds ratio (OR) was 12 (95% CI: 3.8-41.6) for neuropathic pain. Additionally, cold detection threshold/warm detection threshold ratio correlated with the presence of neuropathic pain (ρ = -0.4, P < 0.001). Correlations were found between specific neuropathic pain symptom clusters and quantitative sensory testing: paroxysmal pain with cold (ρ = -0.4; P = 0.008) and heat pain thresholds (ρ = 0.5; P = 0.003), burning pain with mechanical detection (ρ = -0.4; P = 0.015) and mechanical pain thresholds (ρ = -0.4, P < 0.013), evoked pain with mechanical pain threshold (ρ = -0.3; P = 0.047). Logistic regression showed that the combination of cold hypoesthesia on quantitative sensory testing, the Neuropathic Pain Symptom Inventory, and the allodynia intensity on bedside examination explained 77% of the occurrence of neuropathic pain. These findings provide insights into the clinical-psychophysics relationships in central post-stroke pain and may assist more precise distinction of neuropathic from non-neuropathic post-stroke pain in clinical practice and in future trials.

Be in it for the Long Haul: A Commentary on Human Tissue Recovery Initiatives.

The strong need for a new foundational molecular framework for human nervous system research at the nociceptive level is now matched by comprehensive and quantitative capabilities for analyzing nociceptive tissues such as pathologic peripheral tissue, damaged peripheral nerve, dorsal root ganglia, spinal cord, and brain, where possible. However, this idea must be matched by equally strong organization and infrastructures for multisite tissue recovery, molecular analyses, data sharing, and long-term archiving. Experience from other human tissue analysis projects shows that a decades-long activity may be expected, hence "Be in it for the long haul." While certain milestones can be met fairly quickly, others aimed at molecular and neuroanatomical characterization of chronic pain disorders will require the sustained attention of the groups involved. This can yield a valuable addition to basic and translational pain research and the development of new treatments whose targets are validated directly in humans. PERSPECTIVE: A concerted effort is needed to build human nociceptive tissue banks for multi-omic research. In addition to collecting tissue, a careful characterization of pain problems from donors is essential, as is a parallel effort to assess their concurrent medical problems, medications, and the many variables of general human activity and lifestyle that can impact the results. Given the projected long time frame, in addition to maintaining funding, sustaining motivation and momentum are critical factors for success.

Exploring pain phenotypes in workers with chronic low back pain: Application of IMMPACT recommendations.

Background: Chronic low back pain (CLBP) is a major cause of disability globally. Stratified care has been proposed as a means to improve prognosis and treatment but is generally based on limited aspects of pain, including biopsychosocial drivers. Aims: Following Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations, the present study explored pain phenotypes with a sample of workers with CLBP, a population for which no pain phenotypes have been derived to date. Methods: A cross-sectional design was used with a sample of 154 workers with CLBP attending a rehabilitation clinic, recruited in person and from social media. Latent class analysis was used to identify subgroups of patients with different pain profiles based on ten pain indicators (pain variability, pain intensity, pain quality, somatization, sleep quality, depression, fatigue, pain catastrophizing, neuropathic pain, and central sensitization). Results: The majority of the sample (85%) were recruited through social media. Both the two-class and three-class solutions were found to be satisfactory in distinguishing phenotypes of workers with CLBP. Three variables proved particularly important in distinguishing between the pain phenotypes-pain quality, fatigue, and central sensitization-with higher scores on these indicators associated with pain phenotypes with higher pain burden. Increased chronic pain self-efficacy, work-related support, and perceived work abilities were protective risk factors for being in a higher pain burden class. Conclusions: The present study is the first to explore IMMPACT recommendations for pain phenotyping with workers with CLBP. Future prospective research will be needed to validate the proposed pain phenotypes.

Contexte: La lombalgie chronique est une cause majeure d'invalidité dans le monde. Les soins stratifiés ont été proposés comme un moyen d'améliorer le pronostic et le traitement, mais reposent généralement sur des aspects limités de la douleur, y compris des facteurs biopsychosociaux.Objectifs: Suite à l'initiative sur les méthodes, la mesure et l'évaluation de la douleur dans les essais cliniques (IMMPACT), la présente étude a exploré les phénotypes de la douleur à l'aide d'un échantillon de travailleurs atteints de lombalgie chronique, une population pour laquelle aucun phénotype de douleur n'a été déterminé à ce jour.Méthodes: Un devis transversal a été utilisé avec un échantillon de 154 travailleurs atteints de lombalgie chronique fréquentant une clinique de réadaptation, recrutés en personne et sur les réseaux sociaux. L'analyse des classes latentes a été utilisée pour déterminer des sous-groupes de patients présentant différents profils de douleur en fonction de dix indicateurs de douleur (variabilité de la douleur, intensité de la douleur, qualité de la douleur, somatisation, qualité du sommeil, dépression, fatigue, catastrophisation de la douleur, douleur neuropathique et sensibilisation centrale).Résultats: La majeure partie de l'échantillon (85 %) a été recrutée par le biais des médias sociaux. Les solutions à deux classes et à trois classes se sont révélées satisfaisantes pour distinguer les phénotypes des travailleurs atteints de lombalgie chronique. Trois variables se sont avérées particulièrement importantes pour distinguer les phénotypes de la douleur ­ la qualité de la douleur, la fatigue et la sensibilisation centrale - avec des scores plus élevés pour les indicateurs associés à des phénotypes de douleur avec un fardeau de douleur plus élevé. L'augmentation de l'auto-efficacité relativement à la douleur chronique, le soutien lié au travail et les capacités de travail perçues étaient des facteurs de protection pour la classe du fardeau de douleur plus élevé.Conclusions: La présente étude est la première à explorer les recommandations IMMPACT pour le phénotypage de la douleur chez des travailleurs atteints de lombalgie chronique. Des recherches prospectives futures seront nécessaires pour valider les phénotypes de douleur proposés.