Defining a Novel Mouse Model of Sensorimotor Recovery After Spinal Cord Injury.

Research Report
Population: Not Applicable

Timothy D. Faw, PT, DPT, NCS, Graduate Research Associate, The Ohio State University

Jessica Lerch, PhD, Research Assistant Professor, The Ohio State University

D. Basso, PT, EdD, Associate Director – School of Health and Rehabilitation Sciences, The Ohio State University

Keywords: Plasticity, Spinal Cord Injury, Neuropathic Pain, Genetics


To delineate sensorimotor responses to spinal cord injury (SCI) of a transgenic mouse line where the promoter region of the thymus cell antigen 1 (Thy1) genes drive expression of enhanced green fluorescent protein (EGFP) in subsets of neurons.


Male and female wild-type (WT) and transgenic mice (n=29; Male n=12, Female n= 17)

– Thy1-EGFP/M+ (SCI); n=12

– Thy1-EGFP/M+ (TX); n=3

– Thy1-EGFP/M- Littermate Control (SCI); n=4

– C57BL/6 (SCI); n=10


Severe SCI contusion (SCI) or transection (TX) was performed at T9 in Thy1-EGFP/M+ (TG+), Thy1-EGFP/M- (TG-) littermate controls, and C57BL/6 (WT) mice. Thermal and mechanical sensation was examined prior to and 42 days post injury (dpi) using Plantar Heat and Von Frey Hair Test, respectively. Motor recovery was evaluated in the open field using the Basso Mouse Scale pre-injury, 1 dpi, and weekly to 42dpi. Precise hindlimb motor control during locomotion was tested on a grid walkway. Percent tissue sparing at the epicenter indicated lesion severity.


TG+ SCI groups had significantly greater locomotor performance in the open field compared to historic WT SCI controls by 7dpi (WT SCI = 2.4±0.7, TG+ SCI = 4.8±0.5, TG- SCI = 5.0±0.0; p<.01) and remained higher at 42dpi (WT SCI = 5.6±0.4, TG+ SCI = 6.5±0.3, TG- SCI = 7.5±0.0; p<.01). Precise paw placement was severely impaired in TG+ animals (% success; TG+ SCI Pre = 97.2%±1.0, Post = 6.8±2.5; TG- SCI Pre = 98.8±1.3, Post = 5.8±1.8). Thermal hyperalgesia occurred following SCI and TX (TG+ SCI Pre = 9.2sec±1.0, Post = 5.5±0.7; TG- SCI Pre = 7.6±2.0, Post = 2.3±0.5; TG+ TX Pre = 7.9±0.8, Post = 4.0±0.3; p<.001). Interestingly, mechanical hypoalgesia rather than allodynia emerged after SCI in the Thy1-EGFP/M transgenic mice (TG+ SCI Pre = 0.37g±0.06, Post = 0.89±0.12; TG- SCI Pre = 0.75±0.10, Post = 2.18±0.61; TG+ TX; Pre = 0.67±0.17, Post = 4.33±0.33; p<.001). Tissue sparing was also greater in Thy1-EGFP/M+ SCI animals (WT SCI = 12.9%±2.3; TG+ SCI = 38.8±2.5; p<.001).


Using clinically-relevant SCI, we describe an innovative genetic model which demonstrates hypersensitivity to pain yet hyposensitivity to touch. This divergent profile allows a unique opportunity to examine mechanisms underlying sensory recovery essential to improving quality of life (QOL) for people with SCI. Current experiments aim to determine the location and impact of the Thy1-EGFP transgene insertion and associated mutations.

Clinical Relevance

Neuropathic pain is a devastating and often intractable consequence of SCI in up to two-thirds of patients with many reporting a negative impact on QOL. Here we report divergent sensorimotor recovery after SCI in a transgenic mouse line that, for the first time, allows differential study of sensory pathways involved in neuropathic pain. This model will provide valuable molecular targets for treatment of sensory dysfunction after CNS injury.

Faw, Timothy D., PT, DPT, NCS; Lerch, Jessica K., PhD; Basso, D. Michele, PT, EdD. Defining a Novel Mouse Model of Sensorimotor Recovery After Spinal Cord Injury.. Poster Presentation. IV STEP Conference, American Physical Therapy Association, Columbus, OH, July 17, 2016. Online.