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.

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 aims to:

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

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