Factors Related to Neuropathic Pain following Lower Extremity Amputation

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This retrospective study examined factors linked to neuropathic pain after major lower extremity amputation, including above-the-knee amputation, knee disarticulation, and below-the-knee amputation. Researchers reviewed 1,565 adult patients treated at five hospitals from 2000 to 2018, with an average follow-up of 4.3 years. The main outcome was postoperative neuropathic pain, defined as phantom limb pain and/or symptomatic neuroma documented in the medical record.<br /><br />Neuropathic pain developed in 37% of patients. Phantom limb pain was the most common symptom (34%), while symptomatic neuroma alone was uncommon (1.3%). In multivariable analysis, a more proximal amputation level was associated with higher odds of neuropathic pain, as were younger age, normal creatinine, and a history of psychiatric disease. In contrast, diabetes and hypothyroidism were associated with lower odds of neuropathic pain. Older age also reduced risk.<br /><br />The authors suggest that these findings may reflect differences in nerve regeneration: proximal amputations and younger patients may have greater regenerative potential, while diabetes, chronic kidney disease, and hypothyroidism may impair regeneration and therefore reduce neuropathic pain risk. Psychiatric disease likely contributes through the known interaction between pain and mood disorders.<br /><br />The study supports selective use of active nerve-end management techniques, such as targeted muscle reinnervation and regenerative peripheral nerve interfaces, especially in high-risk patients. These procedures can reduce phantom limb pain, residual limb pain, and opioid use, but require additional surgical resources. The authors propose that risk-stratification could help guide referral and resource allocation, though further research is needed to refine patient selection and understand underlying mechanisms.

Keywords

neuropathic pain

phantom limb pain

major lower extremity amputation

symptomatic neuroma

above-the-knee amputation

below-the-knee amputation

targeted muscle reinnervation

regenerative peripheral nerve interfaces

psychiatric disease

risk stratification