Association of Pain Sensitization and Conditioned Pain Modulation to Pain Patterns in Knee Osteoarthritis

Abstract

for the Multicenter Osteoarthritis Study GroupObjective. To examine the cross-sectional association of ascending pain mechanisms, implicated in pain sensitization, and descending pain modulation with pain patterns and unpredictability of pain.Methods. The Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee osteoarthritis. Peripheral and central ascending pain mechanisms were assessed using quantitative sensory tests, pressure pain thresholds using a handheld pressure algometer (knee/peripheral and wrist/central), and temporal summation using weighted probes (wrist/central). Descending modulation was assessed by conditioned pain modulation using pressure pain thresholds and a forearm ischemia test. Pain patterns were characterized based on responses to the Intermittent and Constant Osteoarthritis Pain questionnaire: 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) combined constant and intermittent pain. A question regarding frequency assessed unpredictable pain. We assessed the association of quantitative sensory test measures to pain patterns using regression models with generalized estimating equations.Results. There were 2,794 participants (mean age 63.9 years, body mass index 29.5 kg/m 2 , and 57% female). Lower pain sensitization by wrist pressure pain threshold (odds ratio [OR] 0.80 [95% confidence interval (95% CI) 0.68, 0.93]) and adequate conditioned pain modulation (OR 1.45 [95% CI 1.10, 1.92]) were associated with having constant AE intermittent pain compared with intermittent pain only. Higher pain sensitization (by pressure pain thresholds and temporal summation) was associated with a higher likelihood of unpredictable pain.Conclusion. Knee pain patterns appear to be related to peripheral AE central facilitated ascending pain mechanisms and descending modulatory mechanisms. These findings highlight the need for a broader approach to understanding pain mechanisms by symptomatic disease progression.

Does pain pattern matter? Association of intermittent, constant, predictable and unpredictable knee pain to patient-reported knee symptom acceptability in knee osteoarthritis

“…Although we did not have information regarding radiographic severity or OA symptom duration, the Spearman correlations across ICOAP pain types indicated that as intermittent knee pain intensifies, the prevalence and severity of predictable and unpredictable intermittent pain, and also constant knee pain increases. These findings are consistent with previous cross-sectional and longitudinal studies that have shown that intermittent knee pain in people with symptomatic knee OA is more prevalent than constant pain, constant pain is associated with worse intermittent pain, and worse intermittent and constant pain are associated with greater structural severity on imaging and higher likelihood of demonstrating features pain sensitization [ [9] , [10] , [11] ]. Longitudinal studies are needed to confirm the evolution of OA knee pain with disease progression.…”

Factors associated with pain pressure threshold in both local and remote sites in knee osteoarthritis

“…Although this is in line with several studies identifying lower PPTs in individuals with OA as compared to their healthy controls, 37 there is still some debate whether nociception as measured by PPTs truly reflects clinical pain. Nielsen et al recently reported that PPTs, when applied to a repetitive stimulation protocol (ie, temporal summation), are significantly correlated with clinical pain intensity in individuals with KOA, suggesting the pain mechanisms of this musculoskeletal condition to be widely related to impaired descending pain inhibition 38,39 . Interestingly, we found that PPT is associated with a subtype of clinical pain score: WOMAC pain, which is measuring the pain severity during daily life activities.…”

Subgrouping of facilitatory or inhibitory conditioned pain modulation responses in patients with chronic knee pain. Explorative analysis from a multicentre trial

“…Since an efficient CPM response may be protective for developing chronic pain (Ossipov et al, 2014), it could be expected that an efficient CPM effect would be associated with better outcomes, for example better self‐reported physical function, which was not supported by our study. In line with this surprising finding, Carlesso et al, (2022) observed that adequate CPM effect was associated with higher likelihood of experiencing constant pain instead of intermittent pain. A constant pain experience could indicate the presence of ongoing pain mechanisms such as sensitization and/or impaired CPM effect.…”

“…Conditioned pain modulation and temporal summation have been proposed to be part of central pain amplification processes related to pain sensitization (Arendt‐Nielsen et al, 2010), possibly explaining the observed association in the facilitatory CPM group (Fingleton et al, 2015). Other studies have failed to find associations between CPM, sensitization and pain outcomes (Cardoso et al, 2016; Carlesso et al, 2022). However, these studies did not take the individual variation in CPM responses into account as suggested necessary in our recent studies (Arendt‐Nielsen et al, 2020; Bie Larsen et al, 2020; Sachau et al, 2022).…”