Robert D Graham1,2, Tim M Bruns1,2, Bo Duan3, Scott F Lempka1,2,4. 1. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. 2. Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA. 3. Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA. 4. Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
Abstract
OBJECTIVE: Dorsal root ganglion stimulation (DRGS) is an effective therapy for chronic pain, though its mechanisms of action are unknown. Currently, we do not understand how clinically controllable parameters (e.g., electrode position, stimulus pulse width) affect the direct neural response to DRGS. Therefore, the goal of this study was to utilize a computational modeling approach to characterize how varying clinically controllable parameters changed neural activation profiles during DRGS. MATERIALS AND METHODS: We coupled a finite element model of a human L5 DRG to multicompartment models of primary sensory neurons (i.e., Aα-, Aβ-, Aδ-, and C-neurons). We calculated the stimulation amplitudes necessary to elicit one or more action potentials in each neuron, and examined how neural activation profiles were affected by varying clinically controllable parameters. RESULTS: In general, DRGS predominantly activated large myelinated Aα- and Aβ-neurons. Shifting the electrode more than 2 mm away from the ganglion abolished most DRGS-induced neural activation. Increasing the stimulus pulse width to 500 μs or greater increased the number of activated Aδ-neurons, while shorter pulse widths typically only activated Aα- and Aβ-neurons. Placing a cathode near a nerve root, or an anode near the ganglion body, maximized Aβ-mechanoreceptor activation. Guarded active contact configurations did not activate more Aβ-mechanoreceptors than conventional bipolar configurations. CONCLUSIONS: Our results suggest that DRGS applied with stimulation parameters within typical clinical ranges predominantly activates Aβ-mechanoreceptors. In general, varying clinically controllable parameters affects the number of Aβ-mechanoreceptors activated, although longer pulse widths can increase Aδ-neuron activation. Our data support several Neuromodulation Appropriateness Consensus Committee guidelines on the clinical implementation of DRGS.
OBJECTIVE: Dorsal root ganglion stimulation (DRGS) is an effective therapy for chronic pain, though its mechanisms of action are unknown. Currently, we do not understand how clinically controllable parameters (e.g., electrode position, stimulus pulse width) affect the direct neural response to DRGS. Therefore, the goal of this study was to utilize a computational modeling approach to characterize how varying clinically controllable parameters changed neural activation profiles during DRGS. MATERIALS AND METHODS: We coupled a finite element model of a human L5 DRG to multicompartment models of primary sensory neurons (i.e., Aα-, Aβ-, Aδ-, and C-neurons). We calculated the stimulation amplitudes necessary to elicit one or more action potentials in each neuron, and examined how neural activation profiles were affected by varying clinically controllable parameters. RESULTS: In general, DRGS predominantly activated large myelinated Aα- and Aβ-neurons. Shifting the electrode more than 2 mm away from the ganglion abolished most DRGS-induced neural activation. Increasing the stimulus pulse width to 500 μs or greater increased the number of activated Aδ-neurons, while shorter pulse widths typically only activated Aα- and Aβ-neurons. Placing a cathode near a nerve root, or an anode near the ganglion body, maximized Aβ-mechanoreceptor activation. Guarded active contact configurations did not activate more Aβ-mechanoreceptors than conventional bipolar configurations. CONCLUSIONS: Our results suggest that DRGS applied with stimulation parameters within typical clinical ranges predominantly activates Aβ-mechanoreceptors. In general, varying clinically controllable parameters affects the number of Aβ-mechanoreceptors activated, although longer pulse widths can increase Aδ-neuron activation. Our data support several Neuromodulation Appropriateness Consensus Committee guidelines on the clinical implementation of DRGS.
Authors: Ashley N Dalrymple; Jordyn E Ting; Rohit Bose; James K Trevathan; Stephan Nieuwoudt; Scott F Lempka; Manfred Franke; Kip A Ludwig; Andrew J Shoffstall; Lee E Fisher; Douglas J Weber Journal: J Neural Eng Date: 2021-11-04 Impact factor: 5.379
Authors: Nishant Verma; Robert D Graham; Jonah Mudge; James K Trevathan; Manfred Franke; Andrew J Shoffstall; Justin Williams; Ashley N Dalrymple; Lee E Fisher; Douglas J Weber; Scott F Lempka; Kip A Ludwig Journal: Front Bioeng Biotechnol Date: 2021-12-20