• Amir Dehdashtian, Jagienka H Timek, Shelby R Svientek, Mary Jane Risch, Jared V Bratley, Anna E Riegger, Theodore A Kung, Paul S Cederna, and Stephen W P Kemp.
• Department of Surgery, Section of Plastic Surgery, The University of Michigan Health System, Ann Arbor , Michigan , USA.
• Neurosurgery. 2023 Nov 1; 93 (5): 119212011192-1201.

BackgroundTreating neuroma pain is a clinical challenge. Identification of sex-specific nociceptive pathways allows a more individualized pain management. The Regenerative Peripheral Nerve Interface (RPNI) consists of a neurotized autologous free muscle using a severed peripheral nerve to provide physiological targets for the regenerating axons.ObjectiveTo evaluate prophylactic RPNI to prevent neuroma pain in male and female rats.MethodsF344 rats of each sex were assigned to neuroma, prophylactic RPNI, or sham groups. Neuromas and RPNIs were created in both male and female rats. Weekly pain assessments including neuroma site pain and mechanical, cold, and thermal allodynia were performed for 8 weeks. Immunohistochemistry was used to evaluate macrophage infiltration and microglial expansion in the corresponding dorsal root ganglia and spinal cord segments.ResultsProphylactic RPNI prevented neuroma pain in both sexes; however, female rats displayed delayed pain attenuation when compared with males. Cold allodynia and thermal allodynia were attenuated exclusively in males. Macrophage infiltration was mitigated in males, whereas females showed a reduced number of spinal cord microglia.ConclusionProphylactic RPNI can prevent neuroma site pain in both sexes. However, attenuation of both cold allodynia and thermal allodynia occurred in males exclusively, potentially because of their sexually dimorphic effect on pathological changes of the central nervous system.Copyright © Congress of Neurological Surgeons 2023. All rights reserved.

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