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Published on: April 20, 2019
Association of Peripheral Serum MicroRNAs With Persistent Phantom Limb Pain in Individuals With Amputation
Manish Bhomia1, Nagaraja Balakathiresan, Min Zhai
1From the Center for Rehabilitation Sciences Research, Uniformed Services University of the Health Sciences, Bethesda, Maryland (MB, MH, PP, JT); The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland (MB, NB, MZ, MH); Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (MB, NB, BK-R); University of Pennsylvania, Philadelphia, Pennsylvania (AA-M); University of California-San Francisco, San Francisco, California (MT, SF); Boston Medical Center, Boston, Massachusetts (BP); Institute of Biomedical Engineering, University of New Brunswick, Fredericton, New Brunswick, Canada (WH); Dalhousie University, Fredericton, New Brunswick, Canada (CO); University Neurosciences-University Health Care System, Augusta, Georgia (SH); Walter Reed National Military Medical Center, Bethesda, Maryland (MH, PP); Department of Neurology, The University of Tennessee Health Science Center, Memphis, Tennessee (JT); and Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, Tennessee (JT).
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.
Insights
Phantom limb pain after amputation may involve microRNAs. This study found 16 microRNAs were significantly increased in individuals experiencing phantom limb pain, suggesting a role in neuropathic pain regulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Phantom limb pain is a common and poorly understood complication following major limb amputation.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various physiological and pathological processes.
Purpose of the Study:
- To investigate the potential role of microRNAs in the pathophysiology of phantom limb pain.
- To identify specific microRNAs associated with the presence and severity of phantom limb pain.
Main Methods:
- Serum samples were collected from 140 adult participants with limb amputations and varying degrees of phantom limb pain.
- MicroRNA expression profiling and bioinformatic analysis were performed on serum samples.
- Pain severity was assessed using the Visual Analog Scale and Neuropathic Pain Symptom Inventory.
Main Results:
- A significant increase in the expression of 16 specific microRNAs was observed in participants experiencing phantom limb pain compared to those without pain.
- Linear regression analysis indicated an inverse relationship between the time since amputation and the severity of phantom limb pain.
- Bioinformatic analysis suggested that these upregulated microRNAs may regulate genes involved in peripheral neuropathy.
Conclusions:
- This study presents the first evidence linking specific microRNAs to phantom limb pain.
- The findings suggest that microRNAs play a role in the development or maintenance of phantom limb pain, potentially through the regulation of genes associated with peripheral neuropathy.
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