Elisabeth Kjær Jensen

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

The transition from a healthy to a persistent severe pain state following otherwise successful elective surgery is a feared complication. Groin hernia repair, previously considered minor surgery, is a standard surgical procedure annually performed on 2,000 individuals per one million residents. A trajectory into persistent severe pain is, unfortunately, seen in 2–4%, severely impeding physical and psychosocial daily functions.

Objectives: Severe persistent post-surgical pain (PPSP) remains a significant healthcare problem. In the third most common surgical procedure in the U.K., groin hernia repair, including 85,000 surgeries, estimated 1,500–3,000 patients will annually develop severe PPSP. While the trajectory of PPSP is generally considered a continuation of the acute post-surgery pain, recent data suggest the condition may develop with a delayed onset. This study evaluated pain-trajectories in a consecutive cohort referred from groin hernia repair-surgeons to a tertiary PPSP-center. Potential explanatory variables based on individual psychometric, sensory, and surgical profiles were analyzed. Methods: Patients completed graphs on pain trajectories and questionnaires on neuropathic pain, pain-related functional assessments, and psychometrics. Surgical records and quantitative sensory testing profiles were obtained. Pain trajectories were normalized, and pre- and post-surgical segments were analyzed by a normalized area-under-the-curve (AUC) technique. Principal component analysis (PCA) was applied to the explanatory variables. Significant PCA-components were further examined using multiple logistic regression models. Results: In 95 patients, the AUC identified groups of post-surgical pain trajectories (pI (n=48), acute high-intensity pain progressing to PPSP; group II (n=28), delayed onset of PPSP; group III (n=7), repeat-surgery gradually inducing PPSP. Data from groups IV (n=3) and V (n=9) were not included in the statistical analysis due to small sample size and data heterogeneity, respectively. The PCA/logistic analyses indicated that neuropathic pain scores, composite pain scores, and pain-related functional assessments were explanatory variables for groups I and II . Conclusions: Pain trajectories in PPSP after groin hernia repair are heterogeneous but can be classified into meaningful groups. Examination of pain trajectories, mirroring the transition from acute to severe persistent post-surgical pain, has the potential of uncovering clinically relevant pathophysiological mechanisms.

Severe persistent pain after groin hernia repair impairs quality-of-life. Prospective, consecutive cohort study including patients with pain-related impairment of physical and social life. Relevant surgical records were obtained, and examinations were by standardized clinical and neurophysiological tests. Patients demonstrating pain sensitivity to pressure algometry in the operated groin underwent re-surgery, while patients with neuropathic pain received pharmacotherapy. Questionnaires at baseline (Q0) and at the 5-year time point (Q5Y) were used in outcome analyses of pain intensity (numeric rating scale [NRS] 0–10) and pain-related effect on the activity-of-daily-living (Activities Assessment Scale [AAS]). Data are mean (95% CI). Analyses were made in 172/204 (84%) eligible patients. In 54/172 (31%) patients re-surgery (meshectomy/selective neurectomy) was performed, while the remaining 118/172 (69%) patients received pharmacotherapy. In the re-surgery group, activity-related, and average NRS-scores at Q0 were 6.6 (5.6–7.9) and 5.9 (5.6–5.9), respectively. Correspondingly, NRS-scores at Q5Y was 4.1 (3.3–5.1) and 3.1 (2.3–4.0; Q0 vs. Q5Y: P < .0005), respectively. Although both groups experienced a significant improvement in AAS-scores comparing Q0 vs. Q5Y (re-surgery group: 28% (4–43%; P < .0001); pharmacotherapy group: 5% (0–11%; P = .005)) the improvement was significantly larger in the re-surgery group (P = .02). This 5-year cohort study in patients with severe persistent pain after groin hernia repair signals that selection to re-surgery or pharmacotherapy, based on examination of pain sensitivity, is associated with significant improvement in outcome. Analyzing composite endpoints, combining pain and physical function, are novel in exploring interventional effects. ClinicalTrials.gov Identifier NCT03713047