Abstract

BackgroundPrevious studies have reported associations between obesity, chronic pain and increased pain sensitivity. The adipokine leptin has been suggested to be involved in the osteoarthritis process as well as in pain sensitisation.ObjectivesThe aim was to study associations between chronic widespread pain, pain sensitivity and leptin in individuals with knee pain.MethodsIn all, 306 individuals with knee pain were included in the Halland osteoarthritis cohort, ClinicalTrials.gov NCT04928170. Of those, 265 were included in this cross-sectional baseline study. The mean age (sd) was 51.6 (8.8) years, and 71% was women. The participants marked their painful areas on a pain figure with 18 predefined areas. They were categorised in three different pain groups according to the modified WP2019 definition (1), with knees excluded (due to highest goodness of fit): Chronic widespread pain (CWP), chronic regional pain (ChRP) if CWP was not met, and no chronic pain (NCP). The group with CWP were compared with those reporting no CWP (ChRP and NCP). The pressure pain thresholds (PPT) were measured using a computerised pressure algometry (AlgoMed, Medoc) on eight predefined tender points (trapezius (bilateral), right second rib, right lateral epicondyle, knees, gluteal (bilateral)) (2). Increased pain sensitivity was defined as having PPT in the lowest third in all tender points. Obesity was measured via waistline measurement and a bioimpedance (InBody 770) measuring BMI and visceral fat area (VFA). Serum-Leptin were analysed with an ELISA method (Alpco). Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to describe the groups.ResultsIn this baseline study, 16% reported CWP, and 15% had low pain pressure thresholds at baseline in the study. Those fulfilling CWP were more often women, had higher BMI, VFA, and increased leptin levels and worse KOOS in four of five subscores, see Table 1A. The age and gender-adjusted leptin levels were 21.6 ng/ml (95% CI 18.2-25.0) in the group with no CWP vs. 35.5 ng/ml (95% CI 27.6-43.4) in the CWP group, p=0.002. In a logistic regression adjusting for age and gender, leptin was associated with reporting CWP OR 1.015 (95% CI 1.004-1.027, p= 0.008).Table 1.A Comparisons between those without CWP and those fulfilling CWP and table 1B comparisons between those not having low PPT and those with low PPT.ABNo CWPMean (sd)CWPMean (sd)p-valueNot Low PPTMean (sd)Low PPTMean (sd)p-valuen2104022639Age51.8 (8.7)52.8 (7.6)0.46552.1 (8.5)48.8 (9.9)0.030Gender, female n(%)67900.00472670.524BMI (kg/m2)26.2 (4.6)28.0 (5.0)0.02226.4 (4.9)27.5 (4.3)0.213VFA (cm2)107 (50)137 (56)0.001110 (54)127 (49)0.088Leptin (ng/ml)21.0 (23.9)39.0 (36.6)<0.00123.0 (26.0)31.8 (31.6)0.061CRP (mg/L)1.9 (2.7)2.2 (2.3)0.6022.0 (2.7)1.9 (1.8)0.825KOOSPain (0-100, worst to best)74 (15)61 (17)<0.00173 (15)65 (18)0.002Symptom (0-100, worst to best)72 (17)64 (18)0.01671 (17)67 (19)0.188ADL (0-100, worst to best)84 (13)69 (19)<0.00184 (14)72 (21)<0.001Sport/rec (0-100, worst to best)49 (26)34 (27)0.00149 (26)36 (25)0.009QoL (0-100, worst to best)53 (18)46 (20)0.05053 (18)45 (21)0.017BMI, body mass index; VFA, visceral fat area; CRP, C-reactive protein; KOOS, knee injury and osteoarthritis outcome score; ADL; function in daily living; sport/Rec, Function in sport and recreation; QOL, knee-related Quality of lifeThe participants with low PPT were younger and had a mean (sd) leptin 31.8 ng/ml (31.6) vs 23.0 (26.0), p=0.061 in the group not having low PPT, Table 1B. In a logistic regression adjusting for age and gender, leptin was associated with low PPT OR 1.016 (95% CI 1.004-1.029, p= 0.012).ConclusionThe pathophysiological mechanism causing widespread pain is probably multifactorial, involving both biological and physical factors. The adipokine leptin could be involved in some of these mechanisms, but longitudinal studies are needed to be able to study causal relationships.

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