Risk Factors for Neuropathic Pain Following Lower Limb Amputation

Neuropathic pain is common following amputation of a lower extremity, with younger age and proximal amputation contributing to increased risk, according to the results of a study published in Plastic and Reconstructive Surgery.

Investigators at Harvard Medical School retrospectively evaluated data from patients (N=1565) who underwent amputation of a lower extremity at 5 hospitals in the Northeastern United States between 2000 and 2018. The prevalence of and potential risk factors for neuropathic pain were evaluated.

The study population comprised 65% men. The mean age of the study participants was 60.4 (standard deviation [SD], 16.2) years, 83% were White, 61% underwent below-the-knee amputation, 38% underwent above-the-knee amputation, and 1.2% underwent knee disarticulation. Indications for amputation included peripheral vascular disease (41%), infection (40%), trauma (9.7%), and oncology (6.2%).

During a mean follow-up of 4.3 years, 34% of patients reported phantom limb pain, 1.3% reported symptomatic neuroma, and 2.5% had both phantom limb pain and neuroma, respectively.

Compared with patients who did not experience neuropathic pain, those with neuropathic pain were younger (mean, 57.0 vs 62.5 years; P <.001), fewer were White (40% vs 61%; P =.008), fewer underwent amputation for peripheral vascular disease (35% vs 65%) or infection (34% vs 66%; P <.001), and they had lower Elixhauser comorbidity scores (median, 6 vs 7; P =.022). Neuropathic pain was also associated with higher mean albumin levels (mean, 3.3 vs 3.1 g/dL; P <.001), and fewer patients with neuropathy had a high creatinine level (30% vs 70%; P <.001), respectively.

In the multivariate logistic regression analysis, neuropathic pain was positively associated with a history of psychiatric disease (odds ratio [OR], 1.6; 95% CI, 1.2-2.1; P <.001) and location of amputation (OR, 1.5; 95% CI, 1.2-1.9; P =.001) and was negatively associated with hypothyroidism (OR, 0.69; 95% CI, 0.50-0.94; P =.019), cardiac disease (OR, 0.70; 95% CI, 0.52-0.93; P =.015), high creatinine levels (OR, 0.77; 95% CI, 0.59-0.98; P =.045), and age (OR, 0.99; 95% CI, 0.98-0.99; P <.001).

This study may have underestimated the prevalence of neuropathic pain, as it was defined by chart review and not patient examination.

Study authors concluded that younger age and proximal amputation location was associated with increased risk for postamputation neuropathic pain, likely due to nerve regenerative potentials. Risk for neuropathic pain was reduced among patients with diabetes, hypothyroidism, and chronic kidney disease. The authors advise that “additional research into the underlying pathophysiologic mechanisms of the factors identified in this study will allow for further advancement in treating postamputation neuropathic pain.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Clinical Pain Advisor