Association Between Experimental Pain Biomarkers and Serologic Markers in Patients With Different Degrees of Painful Knee Osteoarthritis

Abstract

Objective. To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.Methods. The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using the Kellgren/Lawrence [K/L] scale). The following structurally related serologic biomarkers were measured in serum: high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinase (MMP)-mediated breakdown of CRP (CRPM), MMPmediated degradation of type I collagen (C1M), C2M, and C3M. Pressure-pain thresholds (PPT) (peripheral and spreading sensitization), temporal summation of pain, and conditioning pain modulation (CPM) (with the latter 2 biomarkers representing generalized sensitization) were assessed. For each pain parameter, the patients were categorized as most sensitized or least sensitized.Results. Correlations were observed between the pain biomarkers PPT, temporal summation, and CPM and maximal pain intensity during the last 24 hours. Significant associations between most of the serologic biomarkers were observed. A high CRPM level was associated with centralized sensitization (temporal summation and CPM). None of the serologic markers correlated with the intensity or duration of knee pain, and only hsCRP correlated with the K/L grade. The most-sensitized group contained more women than men, and the least-sensitized group contained more men than women.Conclusion. A platform of mechanistic pain biomarkers in combination with structure-related serologic biomarkers provides new possibilities for understanding how osteoarthritis-related structural features may be associated with pain and pain sensitization. This study showed significant correlations between central pain sensitization and CRPM as a possible measure for chronic inflammation. Future pain association studies should include biomarkers representing the local joint environment more specifically.In osteoarthritis (OA), the association between joint damage and pain intensity has not been clearly elucidated (1,2). Although the pain mechanisms and various other factors associated with OA are controversial (3), peripheral and central pain sensitization appear to be involved (4,5). Up to 70% of patients with OA have somatosensory abnormalities (6) involving pain sensitization (7). The implications of sensitization are enhanced responses to a painful stimulation provoked locally (localized peripheral sensitization) and extrasegmentally (central spreading sensitization).Because traditional structural joint markers show

Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis

“…Studies show that serum CRP in patients with knee OA is negatively associated with clinical symptoms such as muscle strength [90] and knee pain at night and when sitting or lying [91]. Serum CRP levels were shown to correlate with KL grade, with the most-sensitized group containing more women than men [92]. Moreover, it was observed that serum CRP levels are higher in erosive hand OA patients than in non-erosive OA patients.…”

Effect of Milnacipran on Pain in Patients with Rheumatoid Arthritis with Widespread Pain: A Randomized Blinded Crossover Trial

“…Several studies have documented the impact of central pain mechanisms in osteoarthritis (10–12), but data regarding the role of central pain mechanisms in RA is scarce. No studies have examined the effects of serotonin norepinephrine reuptake inhibitors (SNRIs) on pain in RA, although some have suggested that tricyclic antidepressants, which exert their effects via serotonin and norepinephrine, are effective (13–15).…”

The Potential Role of Sensory Testing, Skin Biopsy, and Functional Brain Imaging as Biomarkers in Chronic Pain Clinical Trials: IMMPACT Considerations

“…requiring the presence of widespread mechanical hyperalgesia) and neuropathic pain (i.e., requiring the presence of positive or negative sensory signs/symptoms), and while QST is unlikely to play the sole or primary role in the formal diagnoses of conditions such as arthritis, headache, or back pain, it may be useful in identifying common features, mechanisms, and risk factors, according to the parlance of the ACTTION-American Pain Society Pain Taxonomy [60]. For example, individuals with OA have been shown to have lower pressure pain thresholds at the affected joint as well as at a distal site than healthy controls [90, 145, 177], and recent research has identified subgroups of individuals with OA using a combination of sensory testing and serum markers [4, 52]. Other work has linked altered sensory testing with increased brain activation in OA patients, a relationship that was not observed in healthy controls [72].…”