Sensory Sensitivity Over Time After Lower Limb Amputation and Its Association with Phantom Limb Pain

Phantom limb pain (PLP) is a common complication after amputation, yet its underlying mechanisms and longitudinal course remain incompletely understood. Alterations in peripheral sensory processing, as assessed using Quantitative Sensory Testing (QST), have been associated with PLP; however, most existing studies are cross-sectional, and little is known about how sensory function changes over time. To address this research question, the present longitudinal study aimed to characterize changes in sensory sensitivity during the first year after amputation and to examine their association with the presence and intensity of PLP.

This study adopted a longitudinal within-subject design, examining 11 persons with unilateral lower limb amputation (mean age 47 years, n = 7 men, n = 4 women) within the first six months after amputation (T1) and at a follow-up assessment at least six months later (T2). To control for potential day-to-day variability in sensory assessments, we additionally collected data from 11 age- and sex-matched control subjects without amputation at both measurements. Sensory function was assessed using the standardized DFNS QST protocol. Outcome measures included warm detection threshold (WDT), heat pain threshold (HPT), mechanical detection threshold (MDT), mechanical pain threshold (MPT), pressure pain threshold (PPT), wind-up ratio (WUR), mechanical pain sensitivity (MPS) and the presence of mechanical allodynia (DMA). Measurements were conducted at the residual limb and the homologous contralateral body site. Group comparisons were conducted using paired and independent t-tests or their non-parametric equivalents (Wilcoxon signed-rank and Mann-Whitney U-tests), and correlations were assessed using Spearman's rank correlation.

PLP prevalence increased in our cohort from T1 to T2, with three additional amputees classified as having PLP at T2. At T1, amputees with PLP showed a significantly higher WDT and MDT at the residual limb compared to the contralateral body site (resp. p = 0.026, 95% CI [0.08, 0.68]); (p = 0.003, 95% CI [0.37, 0.92]). At T2, MDT at the residual limb in the PLP+ group was significantly higher than in non-amputated controls (p = 0.049, 95% CI [-0.91, -0.002]). Furthermore, within the PLP+ group, higher PLP intensity was positively correlated with MDT at the residual limb at T2 (p = 0.638, p = 0.047). In addition, signs of central sensitization were observed in amputees with PLP compared to Controls and included allodynia at T1 and T2 (resp. T1: p = 0.010, 95% CI [-0.31, -0.06]; T2: p = 0.043, 95% CI [-0.14, -0.01]) as well as a higher wind-up ratio in amputees with PLP compared to amputees without PLP at T2 (p = 0.037, 95% CI [-0.03, 0.5]) indicating enhanced temporal summation of pain.

These findings suggest that PLP is associated with dynamic alterations in peripheral sensory processing at the residual limb and increasing signs of central sensitization over time. Together, the results support the notion that PLP is not solely a consequence of peripheral deafferentation but may reflect an interaction between evolving sensory abnormalities and centrally mediated pain amplification processes.