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NIH grant 1IK2RD001083-01A1: Surgical interventions to prevent and reduce amputation related pain
Institute: {'code': 'VA', 'abbreviation': 'VA', 'name': 'Veterans Affairs', 'admin_org_id': '12500964', 'admin_funding_url': ''}. PI: Gwendolyn Maria Bethenis M Hoben. Award: $.
Start: 2026-10-01T00:00:00.
Significance to VA: From recent combat veterans to the older veterans receiving care for diabetes and
vascular disease at the VA, amputation care is a priority in the VA health system. Targeted muscle
reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNIs) represent a paradigm shift in
amputation care: they can be used at the time of amputation to prevent or significantly reduce both phantom
and residual limb pain. However, for the 50,000+ veterans living with chronic amputations, of whom more than
60% experience pain, these interventions are not as successful in reducing pain. More fundamentally, RPNI
and TMR have not been directly compared under different injury circumstances, preventing strategic use and
potentially, more effective use, personalized to the veteran.
Innovation and Impact: There is minimal preclinical data examining these interventions for pain outcomes.
The PI has developed animal models that closely reflect pain related clinical outcomes of TMR and RPNI to
answer these questions. As a practicing peripheral nerve surgeon, the PI is well equipped to ensure the
highest possible congruity between the animal model and clinical application.
Specific Aims: We will use rodent models of amputation related pain and selective nerve injuries to compare
TMR and RPNI. In Aim 1 they will be applied at the time of injury. In Aim 2, TMR and RPNI will be delayed
allowing the development of subacute to chronic pain from the injury so that we can determine how the
intervention outcomes are affected by pre-existing pain. Aim 3 will examine a known change related to chronic
pain, ectopic sympathetic innervation at the dorsal root ganglia, to determine its roll in intervention outcomes.
Methodology: Evoked pain behaviors, spontaneous pain measures, depression/anxiety tests, and teased fiber
recordings of spontaneous activity will be used to assess pain outcomes related to the interventions. Changes
in sensory neuron populations and protein expression will be assessed with retrograde labeling and
immunohistochemistry.
Path to Translation/Implementation: Translation of this work to clinical trials will be facilitated by the fact that
these interventions are already in clinical use and have undergone in depth evaluation for risk and cost
efficacy. Our findings will better define strategic application of TMR and RPNI that can be evaluated readily in
the VA population.
Environment and Career Development: The Medical College of Wisconsin (MCW) is an ideal environment
for this proposal. There is a strong community of pain researchers with extensive expertise in pain biology, in
vivo teased fiber physiology, and analysis of animal pain behaviors. Dr. Caron Dean Bernhoft, VA associated
mentor, and Cheryl Stucky, MCW associated mentor, have over 50 years combined experience in rodent pain
neurobiology, in vivo electrophysiology measurements and the study of pain mechanisms at the behavioral,
cellular, and molecular levels in a variety of disease and injury models. The PI of this proposal, Dr. Gwendolyn
Hoben, is a fellowship trained peripheral nerve surgeon who uses TMR and RPNI clinically and she is a PhD
trained researcher with background in nerve regeneration, small animal surgery, and immunohistochemistry
experiments. She has been a staff surgeon at the Clement J Zablocki VA for 4 years and has built new clinical
programs for veterans. Her main VA mentor, Dr. Shekar Kurpad, is a surgeon scientist with a long history of
successful VA funding and translational research products and he will mentor Dr. Hoben in her career path.
This proposal will give Dr. Hoben more training in pain neuroscience, electrophysiology techniques,
neuroimaging, grantsmanship, and laboratory leadership. This proposal will provide a foundation to apply for
VA Merit funding and NIH grants. She is excited to build this research program with rigorous basic science to
confidently translate the findings to improve veteran care.document fetched 2026-10-24 02:46