Objective Among adults with persistent post-amputation pain, increased amputated-region pain sensitivity may reflect peripheral sensitization or indicate underlying central sensitization. To determine whether underlying central sensitization may contribute to increased pain sensitivity in this population, this study compared clinical signs and symptoms associated with central sensitization between adults with post-amputation pain who demonstrate or lack increased amputated-region sensitivity (as compared to reference data). Design Cross-sectional. Subjects Ninety-nine adults (60 with a unilateral, transtibial amputation and post-amputation pain, 39 pain-free controls with intact limbs). Methods Participants underwent pain-pressure threshold testing of amputated-region and secondary (non-amputated region) sites and completed outcome measures assessing central sensitization symptoms (Patient-Reported Outcomes Measurement Information System (R) pain intensity and interference domains, Central Sensitization Inventory). Among the full sample, the presence and frequency of specific central sensitization symptoms were evaluated. Participants with post-amputation pain were then grouped based on whether normalized, amputated-region pain-pressure thresholds fell below (i.e., sensitive) or above (i.e., non-sensitive) the 25th percentile of sex-specific reference data. Between-group differences in normalized secondary-site sensitivity were evaluated using a multivariate analysis of variance; central sensitization symptom scores were compared using a Kruskal-Wallis test. Results Noteworthy symptoms associated with central sensitization (e.g., fatigue, sleep disturbance, cognitive difficulty) were reported by 33%-62% of participants. Secondary-site pain sensitivity was greater among individuals with increased amputated-region sensitivity (n = 24) compared to peers without increased amputated-region sensitivity ([n = 36], mean difference > 1.33 standard deviation [SD], p < 0.001). Central sensitization symptom scores, however, were similar between groups (p > 0.187). Conclusions Participants with increased amputated-region sensitivity demonstrate generalized, secondary-site pain hypersensitivity, potentially indicating underlying central sensitization. Central sensitization symptom scores, however, were similar between groups, suggesting differences in physiological pain sensitivity may not manifest in subjective post-amputation pain descriptions.
