TMS and Exercise for Post-stroke Pain

There are over 7 million people living with stroke in the United States. Per year, approximately 17,000 Veterans are admitted to the VA for acute stroke. Chronic pain after stroke can occur between 10-50% of stroke survivors. Post-stroke pain (PSP) can lead to further complications in a stroke survivor's recovery. Exercise has improved PSP and associated symptoms such as mobility, fatigue, and quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique using electromagnetic induction for cortical neurostimulation. The use of rTMS has been explored shown to be effective in treating chronic PSP but is limited in effect duration. Our proposal will test the hypothesis that rTMS is feasible and safe to be paired with exercise. Additionally, the investigators believe a complementary effect can develop to enhance the neurostimulation duration of rTMS.


Eligibility Criteria:
Inclusion Criteria:

* Male or female Veteran of US military 19 years of age
* Signed informed consent
* Minimum of 3-months since time of stroke and medically stable
* Headache has persisted for \>3 months after stabilization of the stroke
* Ability to walk or tolerate recumbent cycle ergometry for 10 mins without assistance
* Stable pain medication regimen for 1 month prior to study
* Females of child-bearing potential (i.e. not postmenopausal or surgically sterile) must be using a medically acceptable method of birth control and should not be pregnant nor have plans for pregnancy or breastfeeding during the study
* Completed diagnostic, maximal graded exercise test including 12-lead ECG and indirect calorimetry (i.e. oxygen uptake, minute ventilation, respiratory exchange ratio, etc.)
* Minimum pain intensity of 30 on the Mechanical Visual Analogue Scale on average with pain symptoms.

Exclusion Criteria:

* Moderate to severe cognitive impairment (Montreal Cognitive Assessment score \<16/30)
* Pre-stroke modified Rankin \>2
* History of seizures
* Presence of any standard TMS or MRI contraindications (see human subjects)
* Current diagnosis of DSM-5-defined bipolar disorder I, schizophrenia, schizoaffective disorder, or obsessive-compulsive disorder
* Diagnosis of moderate or severe substance use disorder (except for caffeine and nicotine) during the preceding 3 months (Participants must agree to abstain from illicit drugs during the study)
* Increased risk of suicide that necessitates inpatient treatment or warrants additional therapy excluded by the protocol; and/or intensity of suicidal ideation (Type 4 or Type 5) or any suicidal behavior in the past 3 months on Columbia Suicide Severity Rating Scale (C-SSRS)
* Litigating for compensation for a psychiatric disorder

  * Veterans who are in the process of applying for or receiving VA service-connected disability are eligible
* Current enrollment in another intervention trial for pain or stroke
* Persons imprisoned, of minor age, diagnosed with terminal illness, or require surrogate for consent
* Fails baseline exercise screening activities
* Persistent post-stroke headaches not better accounted for by another diagnosis
* Is unable to reliably attend intervention sessions i.e. planning to move, transportation issues
* Neurological disorder pre- or post- stroke affecting subject's ability to follow study directions