Strain and Model Differences in Behavioral Outcomes after Spinal Cord Injury in Rat

Abstract

Spinal cord injury (SCI) results in loss of function below the level of injury and the development of chronic central pain (CCP) syndromes. Since different strains may develop and express chronic pain behaviors differently, we evaluated behavioral outcomes (locomotor recovery and the development of mechanical and thermal allodynia) in three commonly used strains of rats (Long-Evans, Wistar, and Sprague-Dawley) using two models of SCI. The two models examined were contusion at T10 (NYU impactor, 12.5 mm height) and the T13 hemisection. Mechanical stimulation (von Frey filaments) revealed significantly lower baseline responses for Long-Evans rats and significantly higher baseline paw withdrawal latencies to thermal stimulation for Wistar rats compared to the other strains. Following contusion SCI, Long-Evans rats had the highest percentage of animals that developed mechanical allodynia (73%), while Sprague-Dawley rats had the highest percentages (75%) following hemisection SCI. Interestingly, the Sprague-Dawley rats had the highest percentage (87%) to develop thermal allodynia following contusion SCI, while 100% of both Long-Evans and Sprague Dawley rats developed thermal allodynia in the hemisection model. Locomotor recovery after SCI was similar for each model in that Long-Evans rats recovered slower and to a lesser extent than the other strains. In each model, Sprague-Dawley rats recovered faster and achieved greater function. Overall, the hemisection model produced a larger percentage of animals that developed CCP and had greater responses to mechanical stimulation. Thus, it appears that strain selection has a greater impact on locomotor recovery and model selection has a greater impact on the development of CCP following SCI. Furthermore, these results suggest that genetic factors may play a role in recovery following SCI.

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury

“…In this study, the onset of excessive grooming behavior was slower in SD males than LE males, but the intensity of excessive grooming was greater in SD males. These results agree with previous reports related to the response to injury that show that SD rats exhibit significantly greater spontaneous pain, in addition to significantly greater mechanical and cold allodynia compared to LE rats (Yoon et al, 1999;Mills et al, 2001). The pattern of increase in neuronal activity of limbic structures in the present study may underlie the enhancement of these neuropathic behaviors in the SD strain after spinal injury.…”

“…The greater baseline activity in the SII, AD, BLA, and PVN of the LE may explain, in part, published reports that LE rats perform better in cognitive tasks (Lindner and Schallert, 1988;Tonkiss et al, 1992;Andrews et al, 1995;Harker and Whishaw, 2002), have higher baseline levels of locomotor activity (Aulakh et al, 1988;Onaivi et al, 1992;van Lier et al, 2003), and show less reactivity to external stimuli (Glowa and Hanson, 1994;Acri et al, 1995;Faraday, 2002). In addition, LE rats are more sensitive to painful stimuli, indicated by lower baseline responses to painful mechanical and thermal stimuli applied to the hindpaw (Mills et al, 2001). It is possible that the differences in basal forebrain activation shown in our study may be in part responsible for differences in behavioral response reported by others.…”

“…Such strain-dependent variability in autonomy has subsequently been confirmed in both rats and mice (Panerai et al, 1987;Devor and Raber, 1990;Cohn and Seltzer, 1991;Carr et al, 1992;Defrin et al, 1996;Mogil et al, 1999). The role of genetic factors in neuropathic pain has also been confirmed in studies looking at spontaneous and/or evoked pain-like behaviors, allodynia, and hyperalgesia in rats or mice with peripheral nerve injury or in different models of spinal cord injury (SCI) (Mogil et al, 1999;Lovell et al, 2000;Mills et al, 2001;Yoon et al, 1999;DeLeo and Rutkowski, 2000;Xu et al, 2001;Wiesenfeld-Hallin et al, 1993;Gorman et al, 2001). …”

“…The development of neuropathic pain after injury to a peripheral nerve or as a result of CNS injury in humans is highly variable (Boivie, 1989;Tasker, 1990;Bennett, 1994). Experimental studies in animals indicate that genetic factors underlie at least some of this variability (Mills et al, 2001;Gorman et al, 2001).…”

Spinal Synaptic Enhancement with Acute Intermittent Hypoxia Improves Respiratory Function after Chronic Cervical Spinal Cord Injury

“…Because rat strain and substrain differences influence the magnitude of respiratory LTF (Fuller et al, 2001b) and the severity of motor and sensory impairment after SCI (Gorman et al, 2001;Mills et al, 2001), the choice of rat strain could influence the ability of intermittent hypoxia to induce pLTF after chronic SCI. To account for this possibility, we studied both inbred Lewis (LW) and outbred Sprague Dawley (SD) rats.…”