Compensatory Failure of Autonomic Regulation in Phantom Limb Pain and Its Correlation with Maladaptive Plasticity: A Cross-Sectional HRV Study in Amputees

Background/Objectives: Chronic pain is associated with autonomic nervous system (ANS) dysfunction. Heart rate variability (HRV) indexes sympathetic–parasympathetic balance and autonomic adaptability. Phantom limb pain (PLP) is prevalent after limb loss, but evidence of ANS dysregulation in chronic PLP is limited. This cross-sectional study examined associations between ANS dysregulation and PLP intensity in amputees and explored links with clinical and psychosocial variables. Methods: Fifty-three adults with chronic PLP (mean age 57.7±15.4; 60% male) were enrolled. Primary exposure was PLP intensity concurrent with HRV time- and frequency-domain metrics. Additional variables included residual limb pain, phantom limb sensations (PLS), and telescoping. The PLP–PLS index was also evaluated. Results: PLP intensity was not significantly associated with frequency-domain HRV measures. Time-domain parameters RMSSD (root mean square of successive differences) and pNN50 (percentage of successive normal RR intervals >50 ms) were lower in the positive PLP–PLS group. In multivariate models, depression, pain-medication use, and body mass index were associated with lower SDNN (standard deviation of NN intervals), RMSSD, pNN50, low-frequency (LF), and high-frequency (HF) power. Female sex and pre-amputation pain correlated with higher LF, whereas traumatic etiology correlated with lower LF. Poor sleep quality correlated with elevated HF. No predictors related to the LF/HF ratio. Conclusions: HRV alterations in PLP were associated with depression and pain-medication use rather than pain intensity. Findings support HRV dysfunction as a marker of brain compensatory failure and central neurophysiological disruption within circuits governing autonomic regulation and maladaptive plasticity, highlighting utility for identifying central dysfunction even when pain severity does not vary.