Abstract
In clinical populations, it can be challenging to identify the underlying mechanisms of chronic pain. Referred pain (RP) from an intramuscular infusion provides a clinically-relevant model of centrally-mediated pain that can be used to investigate factors contributing to nociplastic pain. Further, quantitative sensory testing (QST) is commonly used to assess for central mechanisms. However, it is challenging to validate QST assessments in humans. Thus, the primary purpose of this study was to characterize predictors of RP incidence, including local pain, sex, and multiple QST assessments: pain thresholds (PTs), temporal summation (TS), and conditioned pain modulation (CPM) using heat, pressure and punctate stimuli. 312 adults (162F) completed 4 experimental pain conditions at 2 visits: intramuscular anterior tibialis infusion of acidic (pH 5.2) or normal saline at 40 and 80 ml/hr for 5 min (blocked order). Ankle RP was assessed as pain >1/10. 200 participants also completed a 3rd visit involving the QST. Local and RP increased on average across the 4 conditions. Generalized logit modeling (R) with random slopes and intercepts, and adjustment for age, BMI, negative affect, and infusion condition were used to compute odds ratios (OR). RP incidence increased 5.33 times (OR+/-1.34 SEM, p<0.001) with each 1/10 increase in local pain overall. Women were 5.35 times more likely than men to have RP (OR+/-1.91, p=0.01) overall. Of the multiple QST assessed, only one was a significant predictor; RP was 11.47 times more likely when pressure TS was present (OR+/-2.49, p=0.008). No other QST significantly predicted presesnce of RP. Although various QST have been used as indicators of nociplastic pain in clinical populations, these results suggest that they are not interchangeable. Thus, it may not be valid to use all forms of QST as equivalent metrics for the presence/absence of central pain mechanisms in clinical pain conditions. Grant support from NIAMS R03AR065197.
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