Genetics and Phantom Limb Pain

Objectives:

The proposed clinical trial will investigate the role of the human genome including genetic
variations and gene expression profiles on the development of phantom limb pain (PLP).

Study population:

Patients will be recruited from military personnel with major limb amputations. A total of
one thousand subjects with upper or lower extremity amputations of any level will be
enrolled in this study.

Design:

Eight hundred subjects with chronic PLP (PLP patient) and 200 patients without PLP (non-PLP
patient) will assess the severity of their pain symptom. Each participant will undergo a
routine blood draw from which DNA and RNA will be harvested.

Outcome measures:

Using Affymetrix SNP 6.0 technology, which identifies up to 1 million single nucleotide
polymorphisms (SNPs) and 1 million copy number variations in the human genome, the
differences in genomic variations between the PLP and the non-PLP patients will be analyzed.
An extreme subset of PLP patients will be tested for their quantitative sensory function and
profiled gene expression and epigenetic pattern with the Affymetrix Human Exon ST 1.0 and
Illumina Genome Analyzer IIx. These integrative genomic analyses using genetic variations,
gene expression and epigenetic profile could explain why some amputees experience chronic
PLP and some do not. By studying these responses in patient samples, we will evaluate the
role of genomic factors in PLP. SNP frequencies, gene expression and epigenetic profiles
between PLP and non-PLP groups will be analyzed.

- INCLUSION CRITERIA:

PLP GROUP:

- at least 18 years of age

- Single or multiple upper and/or lower limb amputation

- At least three months post-amputation

- Ability to follow study instructions in English

- Currently present on-going PLP for at least one month and at least 3 times per week

NON PLP GROUP:

-same with PLP group except:

--Experienced PLP less than 10 times total and/or for less than two weeks

EXCLUSION CRITERIA:

BOTH PLP AND NON-PLP GROUPS:

- Chronic systemic disease which might affect pain sensitivity and ability to
participate in this study's blood draw

- Any disease (such as hemophilia) or medication regimen (such as warfarin) increasing
hemorrhage that would make a blood draw dangerous or inadvisable for the subject

- Known uncontrolled systemic diseases; known cancer not in remission, known on-going
infection, lupus, kidney disease requiring dialysis, any other systemic disease which
might affect ability to participate in this study's blood draw

- Inability to provide his/her own informed consent