Establishing a Mouse Model for Neuropathic Pain Elicited by Thoracic Contusion Spinal Cord Injury

Schleicher, Wolfgang

Undergraduate Honors Thesis

Establishing a Mouse Model for Neuropathic Pain Elicited by Thoracic Contusion Spinal Cord Injury Public Deposited

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/z316q209m

Abstract

With a high occurrence of spinal cord injuries (SCIs) per year in the United States, and a significant number of patients living with SCI, innovations in modeling, treating, and managing these injuries is in high demand. An often overlooked aspect of SCI is the management of neuropathic pain. Most notably, the field lacks a well-defined, clinically relevant mouse model for SCI-induced neuropathic pain. Here we tested the hypothesis that a moderate contusion SCI in mice would cause neuropathic pain, and that this pain might be alleviated by inactivating astrocytes. We report significant inductions of acute-to-chronic hyperalgesia and allodynia in both male and female mice, with female mice exhibiting lower thermal nociceptive thresholds than males. Furthermore, locomotor recovery occurred primarily within the acute phase of injury recovery, with little improvement during the chronic phase. We hypothesized astrocytes would play a critical role in the induction of neuropathic pain with SCI based on this timeline. To test this, mice were injected with an inhibitory DREADD viral vector (pAAV-GFAP-HA-hM4D(Gi)-IRES-mCitrine) then subjected to a thoracic contusion SCI. Astrocytes were inactivated by systemic application of clozapine-N-oxide (CNO). We observed few behavioral changes and a lack of GFP expression in the injury epicenter, suggesting DREADD-mediate astrocyte inhibition was ineffective. Although the exact role may be unclear, astrocytes appear to be critical players in mediating neuropathic pain in post-SCI recovery. The model for neuropathic pain developed here also provides a base for developing and refining methods to treat and manage SCI in humans.

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