Poster abstracts
Poster number 94 submitted by Timothy Faw
Abnormal sensorimotor recovery in a transgenic mouse model of spinal cord injury
Timothy D. Faw, PT, DPT, NCS (Neuroscience Graduate Program, The Ohio State University), Jessica K. Lerch, PhD (Department of Neuroscience, The Ohio State University), Samantha D. Kerr (School of Health and Rehabilitation Sciences, The Ohio State University), Rochelle J. Deibert (School of Health and Rehabilitation Sciences, The Ohio State University), Lesley C. Fisher (School of Health and Rehabilitation Sciences, The Ohio State University), D. Michele Basso, PT, Ed.D. (School of Health and Rehabilitation Sciences, The Ohio State University)
Abstract:
Neuropathic pain is a devastating and often intractable consequence of spinal cord injury (SCI) in up to two-thirds of patients with many reporting a negative impact on quality of life (QOL). Neuropathic pain can manifest as pain from normally non-painful stimuli (allodynia) or heightened response to a noxious stimulus (hyperalgesia). In animal models, these symptoms historically track together, preventing mechanistic study. Here we report atypical sensorimotor recovery after SCI in a Thy1-GFP/M mouse line that, for the first time, allows differential study of allodynia and hyperalgesia. To fully characterize the behavioral phenotype, we performed a severe SCI contusion (SCI) or transection (TX) at T9 in Thy1 GFP+ (GFP+) and Thy1 GFP- (GFP-) littermates. Sensory recovery was examined using the Hargreaves Method and Von Frey Hair Test prior to and 42 days post injury (dpi). Motor recovery was evaluated in the open field using the Basso Mouse Scale prior to injury, at 1 dpi, and weekly thereafter until 42dpi. Locomotor performance compared to historic wild-type (WT SCI) was increased by 7dpi in Thy1 SCI animals (WT SCI = 2.4 +/- 0.7, GFP+ SCI = 4.8 +/- 0.5, GFP- SCI = 5.0 +/- 0.0; GFP+ TX = 0.8 +/- 0.4; p<.01) and remained increased at 42dpi (WT SCI = 5.6 +/- 0.4, GFP+ SCI= 6.5 +/- 0.3, GFP- SCI = 7.5 +/- 0.0; GFP+ TX = 1.3 +/- 0.4; p<.01). Thermal sensitivity increased following SCI and TX in all animals (GFP+ SCI Pre = 9.2sec +/- 1.0, Post = 5.5sec +/- 0.7; GFP- SCI Pre = 7.6sec +/- 2.0, Post = 2.3sec +/- 0.5; GFP TX Pre = 7.9sec +/- 0.8, Post = 4.0sec +/- 0.3; p<.001) indicating hyperalgesia. Unlike WT SCI mice, hypoalgesia occurred in the Thy1-GFP/M line (GFP+ SCI Pre = 0.37g +/- 0.06, Post = 0.89g +/- 0.12;GFP- SCI Pre = 0.75g +/− 0.10, Post = 2.18 +/- 0.61; GFP+ TX; Pre = 0.67g +/- 0.17, Post = 4.33g +/- 0.33; p<.001). The degree of hypoalgesia was different between groups at 42dpi (p<.01). Current experiments are underway to examine white matter sparing at the epicenter and coordination assessed by grid walk. Together, these findings demonstrate a novel model of neuropathic pain where clinically relevant SCI results in hypersensitivity to pain yet hyposensitivity to touch. This divergent profile allows a unique opportunity to examine mechanisms underlying both allodynia and hyperalgesia, which are essential to improving QOL for people with SCI.
References:
1. Detloff et al (2008) Exp Neurol 212(2):337–347. 2. Hansen et al (2013) J Neurosci 33(32):13101–13111. 3. Hoschouer et al (2009) Exp Neurol 216(1):22-34. 4. Hoschouer (2010) PAIN 148(2):328–342. 5. Detloff et al (2010) Exp Neurol 225(2): 366-376.
Keywords: Spinal Cord Injury, Neuropathic Pain, Recovery