HRV Biofeedback in Pain Patients

This study fulfills the national Veterans Health Administration/Department of Defense
(VHA/DoD) Task Force recommendation that complementary, integrative therapies for pain
management be provided to Veterans. Chronic pain elicits stress which increases sympathetic
output fostering autonomic nervous system imbalance, an overextended stress response,
fatigue, depression and insomnia. Heart Rate Variability (HRV) is a measure of the interplay
between the sympathetic and parasympathetic nervous systems, and thus is a useful and
easily-measured index of autonomic balance that has a relationship to chronic pain effects.
HRV biofeedback (HRV-B) is a novel, biobehavioral procedure that restores normal autonomic
balance. Through HRV-B, patients increase parasympathetic cardiac output and restore
autonomic balance via induction of 'HRV coherence'. The investigators' pilot study indicated
that HRV-B produced coherence and alleviated self-reported ratings of chronic pain and stress
among Veterans attending the investigators' Pain Clinic. The proposed clinical intervention
will further test hypotheses that HRV-B increases HRV coherence, reduces self-reported pain,
stress, depression, fatigue, and insomnia, and improves cognition among Veterans with chronic
pain.

The specific aims are to: (1) conduct a randomized, sham-controlled, pilot intervention trial
to determine whether HRV-B increases HRV coherence among chronic pain patients (n=40 each for
the HRV-B and sham treatment groups; total N=80 patients); (2) determine whether HRV-B
reduces self-reported pain and stress among chronic pain patients. The primary endpoints
include HRV coherence, pain (Brief Pain Inventory or BPI),and stress (Perceived Stress Scale
or PSS)

Outcomes will be measured at 4 time points. pre-training; post-training, one week after the 6
weekly treatments are over; at 4 weeks follow-up after post-training, and at an 8-week
post-training follow-up (total time of participation is 16 weeks from pre-training to 8 week
follow-up).

Furthermore, chronic stress is associated with disrupted circadian rest/activity rhythms and
domains of quality of life (QoL) including fatigue, insomnia, and reduced physical and social
functioning. Interventions that relieve pain thus represent a novel therapeutic target for
normalizing dysfunctional rest/activity rhythms and these QoL domains among pain patients.
The investigators are also interested in assessing the effects of HRV-B on cognitive function
in pain patients. Thus, the investigators' secondary exploratory objectives are to determine
if HRV-B: (1) improves sleep and rest/activity rhythms; (2) alleviates self-reported fatigue
and depression; and (3) improves cognitive function (reaction time, attention). Circadian
endpoints will be measured as actigraphic parameters of sleep (e.g., duration, efficiency),
and rest/activity (e.g., dichotomy index, interdaily stability), and with the Insomnia
Symptom Questionnaire (ISQ); fatigue will be assessed using the Multi-Dimensional Fatigue
Inventory (MFI), which assesses general physical and mental fatigue and motivation.
Depression will be assessed via the Beck Depression Inventory II (BDI-II). Cognitive function
will be measured with a cognitive battery comprised of the Paced Auditory Serial Addition
Test (PASAT), the Rey Auditory Verbal Learning Test (RAVLT), and the Psychomotor Vigilance
Test (PVT).

Proposed Intervention. HRV-B training will follow a previously established, standardized
protocol. The primary (HRV coherence, pain, stress) and exploratory outcomes (insomnia,
fatigue, depression, cognition). Outcomes will be assessed at 4 time points: pre-training;
post-training, one week after the 6 weekly treatments are over; at 4 weeks follow-up after
post-training, and at an 8-week post-training follow-up (total time of participation is 16
weeks from pre-training to 8 week follow-up). There will be no HRV-B training at the 8 week
follow-up, only assessment. Standardized procedures will characterize HRV coherence and other
frequency- or time-domain HRV measures, and validated instruments will be used to assess pain
and stress. Wrist actigraphy will characterize insomnia via continuous, 24-hour/day personal
monitoring of rest/activity rhythms at 1-week intervals coinciding with the baseline
pre-training (baseline), post-training, and 8-week follow-up assessments. The investigators
will provide portable data-logging devices for practicing HRV-B at home. Sham intervention
subjects will have pulse and respiration monitored but not receive active training; instead
they will view a static, relaxing nature picture on a computer screen.

The investigators will use the Hochberg procedure12 to control false discovery rates at 5%.
Analyses will be based on intent to treat with two-sided tests. The effect of HRV-B on
coherence and other HRV variables will be analyzed using linear mixed models for repeated
measures data from sequential time assessments, and a between-subjects factor to evaluate the
intervention after adjusting for potential confounding factors (e.g., age, standard therapy,
medications, co-morbid disease). Baseline relationships between HRV and endpoints will be
examined using multiple regression models. Few studies have examined the multivariate
relationship between pain, autonomic dysfunction, stress, depression, sleep, rest/activity
rhythms, fatigue, and cognition.

Inclusion Criteria:

- are a Veteran between age 18 or older

- have chronic, non-malignant, neuro-musculoskeletal pain

Exclusion Criteria:

- a history of arrhythmia requiring medication or hospitalization

- a pacemaker or automatic implantable cardioverter-defibrillator

- a history of ischemic heart disease, heart transplant, cardiovascular surgery within 1
year

- congestive heart failure

- uncontrolled hypertension

- an active prescription for certain heart medications

- a history of seizures or use of antiseizure or anticonvulsant medication

- moderate or severe head injury or stroke

- evidence of active substance abuse or dependence (alcohol or tobacco use is not be an
exclusion, participants will be asked to provide information about these behaviors in
the investigators' questionnaire)

- a history of bipolar, psychotic, panic or obsessive-compulsive disorder (note:
depression is an exclusion)

- cognitive impairment (dementia), neurocognitive deficits, or a central nervous system
or neurological disorder (e.g., Gulf War Syndrome)

- a current or pending worker compensation claim or personal injury litigation related
to the participants' symptoms