Individualized MRI-Neuromodulation: An intervention for persistent post-mastectomy pain after lymph node dissection.
Introduction
Our long-term goal is to alleviate chronic neuropathic pain in patients treated for breast cancer (BCA) by individualized MRI-neuromodulation (iNM). Although 85% of patients with breast cancer currently live >5 years due to improved treatment, 60% of them develop chronic post-mastectomy pain syndrome (PMPS). PMPS is thought to be caused by sensitization of peripheral and primary afferent receptors, producing a crippling neuropathic pain on the anterior thorax, axilla, shoulder, and/or upper arm. This debilitating pain affects inspiration, expiration, and movement of the trunk, thereby affecting physical and mental health, with 54% of patients reporting changes in employment, and an inability to seek medical care. Physical therapy, myofascial hypnosedation, and stress management training, along with various pharmacological agents, have all failed to effectively alleviate PMPS. New therapies are urgently needed.
Methods
To optimally neuromodulate pain, we have developed an individualized intervention designed to target the circuitry of each patient’s unique anatomical and functional brain areas (1mm resolution) that respond to arm motor and sensory/pain control, guided by extracting optimal time-resolved fMRI signals to effectively manage symptoms, as a function of lymph node dissection extents, afferent nerves lesioned, and brain networks involved (U.S. Patent Application No. 16/954,256)[33-37]. Thus, our intervention is innovative at three levels: 1) Conceptually, in its use of a whole-network approach to treat arm pain by targeting brain pain and motor areas that directly control arm pain, as a function of movement by MRI-guided neuromodulation; 2) Technologically, as we have developed a custom in-house, individualized real-time fMRI closed loop neuromodulation to measure changes in oxy- to de-oxygenated ratios of hemoglobin magnitude and spatial extent of the pain and motor networks (reflecting modulation of synaptic efficacy, a function of neuronal and synaptic firing); and 3) Computationally, as we have developed spatiotemporal causal modeling to associate brain states across motor, sensory and pain networks with arm strength and pain scores.
Results
Our neuromodulation is designed to extract maximum or minimum time-resolved signal intensity segments generated from the control condition and reinforces (motor network signal) or inhibits (pain network signal) them, respectively. For example, a 60% downregulation of pain network signal intensity and extent in the control condition will correspond to a 50% downregulation of the pain network’s oxygenated Hb intensity in the neuromodulation condition (i.e., increasing the physiologic response threshold will further downregulate the pain networks activated with arm motor control). The opposite will be true for motor networks, as we want to increase their signal intensity. Intensity signals are communicated to the patient every 2 seconds via the neuromodulation interface.
Conclusion
This innovative intervention is designed to assess whether iNM can: 1) increase arm strength by upregulating individual brain motor areas that control arm movement and measuring the HbO2's magnitude of the area under the curve (AUC), and the variance in the cortical motor network; and 2) reduce pain by downregulating (neuronal/synaptic firing inhibition) cortical sensory areas. Our immediate goal is to apply this intervention to BCA patients with PMPS to alleviate their neuropathic pain.