Mads Utke Werner

Objectives: The audit explores adherence to the Danish Health Authorities’ recommendations of assessment, diagnosis, and treatment domains in five tertiary multidisciplinary pain centers in three of five regions in Denmark. Methods: We conducted a systematic clinical audit of medical records from 100 patients with high-impact chronic pain (HICP), sampling 20 records at each center. A structured checklist, based on national guidelines, examined the documentation prevalence across bio-psycho-social issues, pain mechanism identification, and treatment, including non-pharmacological and pharmacological interventions, and discharge planning. Guideline adherence and inter-center variations were examined. Data are presented as median (IQR). Results: The patient age was 51 (42–59) years, and 63 % were females. The median treatment duration was 35 (17–50) weeks, with 14 (6–23) healthcare contacts involving 3.1 (2.7–4.0) healthcare professions per patient. Documentation of the target issues in the medical records was as follows: physical examination 37 % (1–17/center), psychological factors 65 % (5–20/center), socio-economic factors 98 % (19–20/center), pain mechanisms 66 % (3–17/center), non-pharmacological treatments 89 % (14–20/center), group treatment 57 % (3–17/center), analgesic consumption at referral 96 % and at discharge 83 %, add-on pharmacological treatments 69 % (8–18/center), opioid use at referral 38 % (4–11/center), and weaning off during treatment 18 % (2–6/center), non-evidence-based pharmacological treatments 21 % (0–12/center), prospective treatment plans in discharge reports 14 % (2–4/center), and overall assessment of patients’ satisfaction with treatment outcomes 40 % (3–11/center). Conclusions: While socio-economic and psychological assessments, and multidisciplinary, non-pharmacological treatments seemed adequately documented, a wide inter-center variation in the documentation of physical examination, diagnostic, pharmacological, and discharge procedures was observed. Standardizing documentation practices is essential to improve consistency and quality of care in Danish multidisciplinary pain centers.

Background: Persistent severe intensity pain after groin hernia repair (PSPG; 200–400/10,000 repairs) is a significant surgical complication impacting the activity of daily living (ADL) and psychosocial functioning. This PhD synopsis presents an outline and a summary of three clinical studies examining outcomes and pathophysiology behind the post-surgical pain state. Objective: The studies assessed (I) treatment outcomes, i.e., re-surgery with meshectomy and selective neurectomy vs pharmacotherapy, (II) temporal trajectories of pain intensity following the primary repair, and (III) somatosensory profiles before and after re-surgery. Methods: On a national basis, patients experiencing PSPG (>3 months) with an activity-related or maximal pain intensity >7 (NRS; 0–10) referred to our unit were examined. Validated questionnaires classifying NRS, ADL functions, and psychometrics, and standardized quantitative sensory testing assessing somatosensory phenotypes were used. Study I was a prospective, questionnaire-based cohort analysis comparing outcomes from a 5-year perspective. Study II retrospectively examined patient-reported pain intensity trajectories. Study III followed somatosensory outcomes before and after re-surgery. Results: In Study I (responder ratio: 172/204 [84%]), patients were allocated to re-surgery ( n = 54) or to pharmacotherapy ( n = 118). Compared to baseline, both cohorts showed significant improvements in pain intensity and ADL functions ( P < 0.0001), with a slight superiority in ADL functions for the re-surgical cohort ( P = 0.02). The number needed to operate for one patient to achieve a positive outcome (≥25% change in NRS/ADL) ranged between 1.5 and 1.9, and for experiencing a negative outcome, between 14 and 28. Study II ( n = 95) identified two main prototypes of post-surgical pain intensity trajectories, where 51% experienced undiminished pain after the primary repair, while 29% experienced normal post-surgical recovery followed by late development of PSPG. Study III ( n = 60) indicated that re-surgery was associated with a loss in the cutaneous somatosensory function and deep mechanical nociceptive function (decrease in evoked pain sensitivity). Summary: The thesis corroborates that both re-surgical intervention and pharmacotherapy may ameliorate high-intensity pain and increase ADL functions in PSPG. Since the study design cannot account for non-specific therapeutic effects, a high-quality RCT is still needed. The pathophysiologic results indicate that the implanted mesh acts as a “pain generator”, and future research should be targeted at dampening the immuno-inflammatory response to the implanted mesh.

Article Stellate ganglion block for mental disorders – too good to be true? was published on January 1, 2025 in the journal Scandinavian Journal of Pain (volume 25, issue 1).

Article Quantitative sensory testing – Quo Vadis? was published on January 1, 2025 in the journal Scandinavian Journal of Pain (volume 25, issue 1).

A novel microparticle‐based extended‐release local anaesthetic containing a bupivacaine/poly‐lactic‐co‐glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first‐in‐human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose‐ascending manner (150‐ to 600‐mg bupivacaine). Subjects were admitted 24 h post‐injection and followed for 30 days post‐injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81–52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69–9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52–8.16; P = 0.004) and 4.00 (0.72–24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4–13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600‐mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post‐injection) coinciding with plasma peak bupivacaine concentrations (490–533 ng/ml). Both LIQ865 formulations demonstrated dose‐dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications.

Article Christmas greetings 2024 from the Editor-in-Chief was published on January 1, 2024 in the journal Scandinavian Journal of Pain (volume 24, issue 1).

Purpose: After groin hernia repair (globally more than 20 million/year) 2– 4% will develop persistent severe pain (PSPG). Pain management is challenging and may require multimodal interventions, including re-surgery. Quantitative somatosensory testing (QST) is an investigational psychophysiological tool with the potential to uncover the pathophysiological mechanisms behind the pain, ie, revealing neuropathic or inflammatory components. The primary objective was to examine and describe the underlying pathophysiological changes in the groin areas by QST before and after re-surgery with mesh removal and selective neurectomy. Patients and Methods: Sixty patients with PSPG scheduled for re-surgery and with an inflammatory “component” indicated by blunt pressure algometry were examined in median (95% CI) 7.9 (5.8– 11.5) months before and 4.0 (3.5– 4.6) months after re-surgery. The QST-analyses included standardized assessments of cutaneous mechanical/thermal detection and pain thresholds. Suprathreshold heat stimuli were applied. Deep tissue sensitivity was tested by pressure algometry. Testing sites were the groin areas and the lower arm. Before/after QST data were z-transformed. Results: Re-surgery resulted in median changes in rest, average, and maximal pain intensity scores of − 2.0, − 2.5, and − 2.0 NRS (0/10) units, respectively (P = 0.0001), and proportional increases in various standardized functional scores (P = 0.0001). Compared with the control sites, the cutaneous somatosensory detection thresholds of the painful groin were increased before re-surgery and increased further after re-surgery (median difference: 1.28 z-values; P = 0.001), indicating a successive post-surgical loss of nerve fiber function (“deafferentation”). Pressure algometry thresholds increased after re-surgery (median difference: 0.30 z-values; P = 0.001). Conclusion: In this subset of patients with PSPG who underwent re-surgery, the procedure was associated with improved pain and functional outcomes. While the increase in somatosensory detection thresholds mirrors the surgery-induced cutaneous deafferentation, the increase in pressure algometry thresholds mirrors the removal of the deep “pain generator”. The QST-analyses are useful adjuncts in mechanism-based somatosensory research.

Article Abstract for the special issue was published on September 29, 2022 in the journal Scandinavian Journal of Pain (volume 0, issue 0).