Pre-treatment pain sensitivity is associated with outcome following exercise therapy in patients with knee osteoarthritis - an observational study

Abstract

Purpose: Exercise therapy in combination with education is recommended as first-line treatment for painful knee osteoarthritis (KOA). In clinical practice, supervised exercise therapy and education demonstrate approx. 25% pain relief following an 8-week treatment program. Studies indicate that some patients with KOA experience larger pain relief compared to others. Assessments of peripheral and central pain mechanisms has been used to predict responders and non-responders to treatment. Studies on surgery and treatment with non-steroid anti-inflammatory drugs in patients with KOA have indicated that patients with higher levels of pain sensitivity might respond less positive. The primary aim of this observational study was to investigative if measures of pre-treatment pain sensitivity was associated with clinical outcomes after supervised exercise therapy and education. Methods: Patients with painful KOA (numeric rating scale [NRS, 0-10] ≥ 3) were included, and examined before and 1-2 weeks after 6-8 weeks of supervised exercise therapy (2 sessions of 1 hour per week) and 2 sessions of patient education. Handheld pressure pain threshold (PPT) was assessed locally at the most painful knee at 4 peripatellar sites (knee) and at two remote sites at the m. tibialis anterior (TA) and the contralateral m. extensor carpi radialis longus (ECRL). Further, computer-controlled cuff algometry at the lower leg with the most intense knee pain was used to assess pain detection threshold (cPDT), pain tolerance threshold (cPTT) and conditioned pain modulation (cCPM). Peak pain intensity within the last 24 hours (NRS, 0-10), PainDetect questionnaire (PDQ, 0-38) and Knee injury and Osteoarthritis Outcome Score (KOOS) were assessed as clinical measures. PDQ assesses the pain phenotype with a score ≤ 12 indicating probably nociceptive pain, 13-18 uncertain pain phenotype and ≥ 19 probably neuropathic pain. KOOS4 was defined as the average score of the subscale scores for Pain, Symptoms, Activity of Daily Living and Quality of Life (0-100 with 0 indicating extreme problems and 100 indicating no problems). Physical performance was assessed using the 40-meter walk test (40MWT). A treatment attendance score (%) was calculated for each patient by dividing the number of sessions attended by the number of sessions scheduled (twice per week). This study was approved by the local ethical committee (N-20190045) and pre-registered at clinicaltrials.org (NCT04123756). All participants gave oral and written informed consent prior to enrollment. Results: This interim analysis reports on the first patients recruited for this observational study. Eleven KOA patients (6 women) with mean peak pain intensity of 6.0 ± 1.5, median pain duration 17.0 months (range: 5-120) and body mass index of 30.3 ± 5.7 were included in this interim analysis. In one subject, follow-up was made by telephone due to the COVID-19 situation, leaving 10 subject for the analysis on changes in pain sensitivity measures. Attendance score was 98.1 ± 18.1% during 7.1 ± 0.7 weeks. Following treatment, improvements were observed in KOOS4 (57.1 ± 10.0 at baseline vs. 65.3 ± 13.1 at follow-up, P < 0.01), and peak pain intensity (6.0 ± 1.5 vs. 3.2 ± 2.3, P < 0.001). No differences were seen for PDQ (7.6 ± 2.6 vs 6.8 ± 3.6, P = 0.77) and 40MWT (27.1 ± 6.6 sec vs. 25.8 ± 5.2 sec, P = 0.29). Further, no changes in any of the pain sensitivity measures were found following treatment (all Ps > 0.15). Pre-treatment cPDT (rs < 0.73, P < 0.05) and cPTT (rs < 0.72, P < 0.05) were associated with post-treatment KOOS4. No significant associations were found between pre-treatment PPT or CPM effects and post-treatment peak pain measures or change in KOOS-4 (P > 0.05). Conclusions: These results indicate that patients with higher pre-treatment pressure pain sensitivity have worse KOOS4 scores following supervised exercise therapy and education.