Feasibility Study: fMRI Evaluation of Auricular PENFS for Fibromyalgia

BACKGROUND: Fibromyalgia is a chronic pain syndrome that consists of chronic widespread pain,
decreased physical function, fatigue, psychoemotional/sleep disturbances, and various somatic
complaints, affecting anywhere from 5-10 million Americans, with ~1,500 Veterans carrying a
diagnosis of fibromyalgia seen per year at the Atlanta VAMC alone. It is estimated that
fibromyalgia costs the American population over $20 billion/year in lost wages and
disability. Initial therapies often include complementary and alternative medicine (CAM)
therapies, which are generally considered safe, although their efficacy has not been
thoroughly evaluated for fibromyalgia. Thus, non-pharmacologic alternatives require more
rigorous scientific investigation for the treatment of fibromyalgia. There is evidence to
support the use of percutaneous electrical neural stimulation (PENS) in the treatment of pain
conditions, which may have increased effects relative to acupuncture based on systematic
reviews. While fMRI data for acupuncture and fibromyalgia exists, no such data exists for
PENS treatment. An evolved form of PENS, percutaneous electrical neural field stimulation
(PENFS) of the auricle is already used in the military and VA systems for the treatment of
chronic pain, but evidence regarding its mechanisms and effects is lacking. Stimulation of
the vagus nerve, which has auricular branches, has been previously studied for pain relief in
fibromyalgia. However, application of PENS-type stimulation to the auricle has not been
previously studied with fMRI, and this type of therapy may lead to neural changes worthy of
further exploration. OBJECTIVE: To evaluate the feasibility of using fMRI as a biomarker for
the neural substrates of pain and functional changes following PENFS treatments. HYPOTHESIS:
PENFS will result in decreased functional connectivity between the insula and default mode
network as evaluated by fMRI, which will correlate to more significant improvements in pain
and function relative to standard therapy for fibromyalgia. METHODS: Subjects who meet study
criteria will receive baseline assessments including resting state fMRI, collection of
biobehavioural information such as cognitive and psychological assessments on standardized
forms, eating, sleeping and drinking habits, Defense and Veterans Pain Rating Scale (DVPRS),
PROMIS measures, arm curl, 30-s chair stand, and handgrip strength tests, [measures from the
realms "Activity and Participation" from the International Classification of Functioning,
Disability, and Health,] and baseline analgesic consumption. Subjects will be stratified
based on age and gender and then divided into standard therapy control (medication management
and physical therapy) or PENFS (series of 4, weekly) treatments and assessed for fMRI changes
2 weeks after the final treatment. Pain and function will also be assessed at the 2 weeks, 6
weeks and 12 weeks following the final treatment. CLINICAL RELEVANCE: [Auricular PENFS has
not been studied with fMRI. Stimulation of the auricle may produce neural changes that differ
from traditional therapies. Understanding the underlying neural mechanisms of auricular PENFS
could assist in developing targeted treatments for fibromyalgia and chronic pain.] Further,
if PENFS can significantly improve pain relief and function over standard therapies, it could
decrease the need for opioid analgesics and their associated risks, which is a primary
objective of the VA Opioid Safety Initiative. The present investigation will not only serve
to elucidate neural changes with PENFS, but could be directly applicable to our Veterans
suffering from fibromyalgia by providing evidence regarding the relative effectiveness of
this already clinically-employed non-pharmacologic treatment (or lack thereof), and result in
evidence-based implementation and potential cost savings to the VA system.

Inclusion Criteria:

- Subjects must be male and female Veterans age 20-60 with a diagnosis of fibromyalgia
as diagnosed by a clinician, by chart review, and by the most recent American College
of Rheumatology 2010 criteria for the diagnosis of fibromyalgia. 70,71

- Subjects must self-report consistent, daily pain (greater than 5 on the VAS) >90 days.

- Subjects must have intact skin free of infection at the site of implantation.

- Subjects must be willing to participate and understand the consent.

- Subjects must be right-handed in order to provide consistency in brain structure and
function.

Exclusion Criteria:

- Subjects must not be currently pregnant, since effects of fMRI and electrical current
on the developing fetus are not well-known.

- Subjects must not have an implanted electrical device such as a vagal stimulator,
pacemaker, or spinal pain pump, which are not compatible with MRI.

- Subjects must not have a history of seizures or neurologic condition that may alter
the structure of the brain.

- Subjects must not have a history of drug abuse or severe, uncontrolled psychiatric
illness such as schizophrenia or major depressive disorder with suicidal ideation.

- Subjects must not have psoriasis vulgaris or other skin conditions that may increase
the risk of infection at the implantation site.

- Subjects must not have severe anxiety, claustrophobia, or other conditions that may
prevent their ability to lie at rest in an MRI scanner. This will be determined after
discussion with the patient regarding their own perceived ability to lie at rest in an
MRI scanner without the use of additional sedating medications.

- Subjects must not introduce new medications or treatments for fibromyalgia symptoms
during the course of the study to prevent confounding results.

- Subjects must not have a concurrent autoimmune or inflammatory disease that causes
pain such as systemic lupus erythematosus, inflammatory bowel disease or rheumatoid
arthritis, since this could decrease the effect of treatment.