Association of Peripheral Serum MicroRNAs with Persistent Phantom Limb Pain in Individuals with Amputation

Manish Bhomia*, Nagaraja Balakathiresan, Min Zhai, Aimee Alphonso-Morrison, Monica Tung, Sacha Finn, Briana Perry, Wendy Hill, Colleen O'Connell, Steven Hanling, Morgan Hunt, Paul Pasquina, Jack Tsao, Barbara Knollmann-Ritschel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective Individuals with major limb amputation(s) frequently experience phantom limb sensations, which are described as vivid impressions of either parts or entire missing limb(s). Despite the high incidence and prevalence of phantom limb pain, the underlying pathophysiology of phantom limb pain remains poorly understood. The objective of this study was to evaluate a possible role of microRNAs in the pathophysiology of phantom limb pain. Design Adults with acquired limb amputation and varying degrees of phantom limb pain consented to provide clinical data and blood samples. One hundred forty participants with single or multiple limb amputation(s) were enrolled. The Visual analog scale and neuropathic pain symptom inventory were administered to evaluate the pain. Serum samples were analyzed for microRNA expression and bioinformatic analysis was performed. Results Sixty-seven participants did not experience phantom limb pain, whereas 73 participants experienced varying severities of phantom limb pain measured on a pain scale. Linear regression analysis suggested that the time since amputation is inversely related to severity of the pain. A significantly increased expression of 16 microRNAs was observed in participants experiencing phantom limb pain. Bioinformatic analysis shows a possible role of these microRNAs in regulating genes expressed in peripheral neuropathy. Conclusions This study provides the first evidence of association of microRNA in phantom limb pain.

Original languageEnglish
Pages (from-to)1139-1147
Number of pages9
JournalAmerican Journal of Physical Medicine and Rehabilitation
Issue number12
StatePublished - 1 Dec 2022
Externally publishedYes


  • Amputation
  • MicroRNA
  • Phantom Limb Pain


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