Association of Post-Amputation Stump Infection with Persistent Residual Limb Pain: A Prospective Cohort Study

Persistent residual limb pain (RLP) is a common and disabling complication following limb amputation. Although nerve injury and neuroma formation are well-established contributors, the potential association between stump infection and long-term pain outcomes has not been fully elucidated.

To evaluate the association between post-amputation stump infection and persistent residual limb pain, with particular emphasis on infection severity, microbiological profile, and antimicrobial resistance.

This prospective observational cohort study included 430 adult patients who underwent upper or lower limb amputation. Stump infection was classified as superficial infection, deep infection, or osteomyelitis and diagnosed using standardized clinical criteria with microbiological confirmation when available. The primary outcome was persistent residual limb pain at 6 months, defined as pain lasting ≥3 months with a Numerical Rating Scale (NRS) score ≥3. Secondary outcomes included pain intensity, neuropathic pain features assessed using the Douleur Neuropathique 4 (DN4) questionnaire, and moderate-to-severe pain (NRS ≥5). Associations between stump infection and persistent RLP were evaluated using unadjusted and multivariable logistic regression analyses.

Stump infection was identified in 118 of 430 patients (27.4%). At 6 months, persistent RLP was more frequent among patients with stump infection than among those without infection. Increasing infection severity was associated with worse pain outcomes, including higher pain intensity and a greater prevalence of neuropathic pain features. Patients with polymicrobial infections, Gram-negative pathogens, and multidrug-resistant organisms (MDRO) demonstrated less favorable pain outcomes than those with uncomplicated microbiological profiles. After adjustment for age, sex, severe soft tissue injury, and time to wound closure, stump infection remained independently associated with persistent residual limb pain.

Post-amputation stump infection was independently associated with persistent residual limb pain in this prospective cohort. Greater infection severity, increased microbiological complexity, and antimicrobial resistance were also associated with less favorable pain outcomes. These findings support the potential clinical importance of early infection recognition and management while highlighting the need for further multicenter studies to clarify the underlying mechanisms and confirm these associations.