# Identification of Procedural, Genetic and Psychosocial Risk Factors for ChronicPost-Amputation Pain

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2024 · —

## Abstract

Chronic Post-amputation Pain (cPAP) is a major unsolved healthcare problem. Every year, Veterans Health
Administration (VHA) hospitals perform 7,000 amputations and civilian hospitals perform approximately
115,000 amputations. Between 50 and 90% of Amputees will suffer from cPAP, with impaired psychological
well-being, physical disability, and a substantially lower quality of life in those patients affected, in addition to
the cost to society at large. Even novel surgical methods such as regenerative peripheral nerve interface
surgery can only modestly reduce, but not prevent, cPAP. Once cPAP has developed, treatment is very difficult
with few therapeutic options. Despite the high clinical relevance, there are still critical gaps in our knowledge of
cPAP and its pathophysiology. Our proposal is focused on addressing three of these gaps using the framework
of the Million Veteran Program (MVP).
The first Specific Aim is to describe the demographics of the MVP Amputee cohort, and the incidence of cPAP
in that cohort. This will be defined as point prevalence 9 (± 3) months after amputation. The complementary
outcome measures are the incidence and severity of cPAP over time, as well as 1- and 5-year mortality. This
will give us a solid understanding of the Amputee cohort within MVP. In addition, we will describe the
perioperative care these patients received around their amputation, and the access to care they had after
surgery, and whether these factors are associated with the development of cPAP. At completion of Specific Aim
1, we will have created a valuable MVP-specific phenotype for well-conducted genetic studies, which will also
facilitate studies by other researchers. We will have also assessed the patterns of practice, the access to care,
and the resulting time-course and severity of cPAP in MVP patients.
The second, and central, Specific Aim of this proposal is to identify genetic variants that are associated with
cPAP risk in MVP patients. This will serve three purposes: first, it will allow us to better understand the genetic
basis for individual risk to develop cPAP; second, it will allow us to describe the congruence of genetic risk
factors between cPAP and diagnoses which we know to influence pain conditions, in particular chronic non-
cPAP pain, anxiety, depression, PTSD, schizophrenia and substance use disorders; and third, this Aim will
shed light on biological-pathway based risk factors specific for cPAP, which may help identify therapeutic or
preventive candidate therapies going forward. At completion of Specific Aim 2, we will have characterized the
influence of genetic factors on the occurrence of cPAP while accounting for genetic risks of highly correlated
psychosocial risks.
The third Specific Aim of this proposal is to examine patient-specific health characteristics, including
psychosocial factors and Social Determinants of Health (SDOH). Despite strong evidence in other domains,
the relationship between psychosocial factors, ...

## Key facts

- **NIH application ID:** 10804861
- **Project number:** 1I01BX006104-01A1
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** JOHN D OTIS
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804861

## Citation

> US National Institutes of Health, RePORTER application 10804861, Identification of Procedural, Genetic and Psychosocial Risk Factors for ChronicPost-Amputation Pain (1I01BX006104-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10804861. Licensed CC0.

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