H-coil TMS to Reduce Pain: A Pilot Study Evaluating Relative Efficacy of the H1 vs H7 Coil
H-coil TMS to Reduce Pain: A Pilot Study Evaluating Relative Efficacy of the H1 vs H7 Coil
Chronic pain is a serious public health problem with estimates as high as nearly half of the
 adult population experiencing some form of pain that lasts for more than 6 months. Chronic
 use of opiates is a rapidly escalating crisis in the United States, with over 4.3 million
 Americans dependent on opiate analgesics, an escalating rate of opiate overdose deaths, and a
 resurgence of intravenous heroin use leading to total societal cost exceeding $55 billion.
 While opiates are effective at treating acute pain, tolerance to the analgesic effects
 develops quickly, leading to high abuse liability and dependence potential. Consequently, the
 development of a new, non-pharmacologic intervention to treat pain, such as repetitive
 transcranial magnetic stimulation (rTMS), which would provide analgesic benefit while also
 directly remodeling the neural circuitry responsible for cognitive control over opiate
 craving, would fill an increasingly urgent public health need.
Chronic pain is a serious public health problem with estimates as high as nearly half of the
 adult population experiencing some form of pain that lasts for more than 6 months. Chronic
 use of opiates is a rapidly escalating crisis in the United States, with over 4.3 million
 Americans dependent on opiate analgesics, an escalating rate of opiate overdose deaths, and a
 resurgence of intravenous heroin use leading to total societal cost exceeding $55 billion.
 While opiates are effective at treating acute pain, tolerance to the analgesic effects
 develops quickly, leading to high abuse liability and dependence potential. Consequently, the
 development of a new, non-pharmacologic intervention to treat pain, such as repetitive
 transcranial magnetic stimulation (rTMS), which would provide analgesic benefit while also
 directly remodeling the neural circuitry responsible for cognitive control over opiate
 craving, would fill an increasingly urgent public health need.

 Acute pain is associated with elevated magnetic resonance imaging (MRI)
 blood-oxygen-level-dependent (BOLD) signal in targets of ascending nociceptive fibers
 including the insula, dorsal anterior cingulate (dACC), thalamus and somatosensory cortex -
 the 'Pain Network'. Perceived pain, and corresponding BOLD signal in the Pain Network, is
 attenuated by 10 Hz rTMS (a form of brain stimulation that results in long term potentiation
 (LTP) to the left dorsolateral prefrontal cortex (dlPFC, a node of the Executive Control
 Network). Dr. Borckardt was the first person to demonstrate that when LTP-like dlPFC rTMS was
 delivered in the postoperative recovery room, patients used less morphine in the hospital and
 require less morphine long-term. These analgesic effects are now widely known, with over 33
 clinical trials utilizing rTMS as a tool to decrease acute and chronic pain in various
 clinical populations.

 These data all suggest that LTP-like DLPFC rTMS is a very strong candidate alleviating
 chronic pain (LTP-like dlPFC rTMS (Strategy 1, Aim 1)). An alternative approach, however,
 *which may also target opiate craving*, is to attenuate the Pain Network (through long term
 depression (LTD) of the ventromedial PFC) (LTD-like mPFC rTMS, Strategy 2, Aim 1). In a
 cohort of 49 individuals with chronic pain, Dr. Hanlon (Primary Investigator) recently
 demonstrated that LTD-like mPFC rTMS reduced baseline BOLD signal in multiple regions of
 interest (ROIs) *involved in craving which also overlap with the Pain Network* (e.g. dACC and
 Insula). To parametrically evaluate these 2 promising treatment strategies, the investigator
 has developed a 1-visit cross-sectional design wherein a cohort of healthy control
 individuals will receive Quantitative Sensory Testing before and after rTMS with the H1 and
 H7-coil for dlPFC stimulation (Strategy 1) and mPFC depression (Strategy 2), respectively.
 The investigator will also measure subjective pain ratings. The investigator aims to:

 Aim 1. Quantify the effects of LTP-like and LTD-like RTMS on Quantitative Sensory Testing
 Hypothesis: The thermal pain tolerance of individuals in these two group will increase after
 one session of rTMS administered by the H1- and H7-coil design relative to sham.

 Aim 2. Evaluate the effects of rTMS on subjective experience of discomfort. Hypothesis:
 Subjective experience of discomfort will decrease relative to sham in individuals after one
 session of LTP-like or LTD-like rTMS administered to the dlPFC and mPFC, respectively.

 The relative efficacy of Strategy 1 vs 2 will directly translate to development of a large
 clinical trial of rTMS as an innovative, new treatment option for pain in opiate dependent
 individuals.
Inclusion Criteria:

 1. Age 18 - 65 (to maximize participation).

 2. Does not have a history of and is currently not experiencing chronic pain.

 3. Able to read and understand questionnaires and informed consent.

 4. Lives within 50 miles of the study site.

 5. Is not at elevated risk of seizure (i.e., does not have a history of seizures, is not
 currently prescribed medications known to lower seizure threshold).

 6. Does not have a history of traumatic brain injury, including a head injury that
 resulted in hospitalization, loss of consciousness for more than 10 minutes, or having
 ever been informed that they have an epidural, subdural, or subarachnoid hemorrhage.

 Exclusion Criteria:

 1. Any psychoactive illicit substance use (except marijuana and nicotine) within the last
 30 days by self-report and urine drug screen. For marijuana, no use within the last
 seven days by verbal report and negative (or decreasing) urine THC levels.

 2. Meets DSM-V criteria for moderate substance dependence, current axis I disorders of
 major depression, panic disorder, obsessive-compulsive disorder, post traumatic stress
 syndrome, bipolar affective disorder, schizophrenia, dissociate disorders, eating
 disorders, and any other psychotic disorder.

 3. Has current suicidal ideation or homicidal ideation.

 4. Has the need for maintenance or acute treatment with any psychoactive medication
 including anti-seizure medications and medications for ADHD.

 5. Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are
 not using a reliable form of birth control.

 6. Has current charges pending for a violent crime (not including DUI related offenses).

 7. Suffers from chronic migraines.