Browsing by Author "Sliwinski, Christopher"

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    Early-onset treadmill training reduces mechanical allodynia and modulates calcitonin gene-related peptide fiber density in lamina III/IV in a mouse model of spinal cord contusion injury
    (Lippincott, Williams, and Wilkins, 2016-03) Nees, Timo A.; Tappe-Theodor, Anke; Sliwinski, Christopher; Motsch, Melanie; Rupp, Rüdiger; Kuner, Rohini; Weidner, Norbert; Blesch, Armin; Department of Neurological Surgery, IU School of Medicine
    Abstract: Below-level central neuropathic pain (CNP) affects a large proportion of spinal cord injured individuals. To better define the dynamic changes of the spinal cord neural network contributing to the development of CNP after spinal cord injury (SCI), we characterized the morphological and behavioral correlates of CNP in female C57BL/6 mice after a moderate T11 contusion SCI (50 kdyn) and the influence of moderate physical activity. Compared with sham-operated animals, injured mice developed mechanical allodynia 2 weeks post injury when tested with small-diameter von Frey hair filaments (0.16 g and 0.4 g filament), but presented hyporesponsiveness to noxious mechanical stimuli (1.4 g filament). The mechano-sensory alterations lasted up to 35 days post injury, the longest time point examined. The response latency to heat stimuli already decreased significantly 10 days post injury reaching a plateau 2 weeks later. In contrast, injured mice developed remarkable hyposensitivity to cold stimuli. Animals that underwent moderate treadmill training (2 × 15 minutes; 5 d/wk) showed a significant reduction in the response rate to light mechanical stimuli as early as 6 days after training. Calcitonin gene-related peptide (CGRP) labeling in lamina III-IV of the dorsal horn revealed significant increases in CGRP-labeling density in injured animals compared with sham control animals. Importantly, treadmill training reduced CGRP-labeling density by about 50% (P < 0.01), partially reducing the injury-induced increases. Analysis of IB4-labeled nonpeptidergic sensory fibers revealed no differences between experimental groups. Abnormalities in temperature sensation were not influenced by physical activity. Thus, treadmill training partially resolves signs of below-level CNP after SCI and modulates the density of CGRP-labeled fibers.
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    Sensorimotor Activity Partially Ameliorates Pain and Reduces Nociceptive Fiber Density in the Chronically Injured Spinal Cord
    (Mary Ann Liebert, 2018-09-15) Sliwinski, Christopher; Nees, Timo A.; Puttagunta, Radhika; Weidner, Norbert; Blesch, Armin; Neurological Surgery, School of Medicine
    A large proportion of patients suffering from spinal cord injury (SCI) develop chronic central neuropathic pain. Previously, we and others have shown that sensorimotor training early after SCI can prevent the development of mechanical allodynia. To determine whether training initiated in the subchronic/chronic phase remains effective, correlates of below-level neuropathic pain were analyzed in the hindpaws 5-10 weeks after a moderate T11 contusion SCI (50 kDyn) in adult female C57BL/6 mice. In a comparison of SCI and sham mice 5 weeks post-injury, about 80% of injured animals developed mechanical hypersensitivity to light mechanical stimuli, whereas testing of noxious stimuli revealed hypo-responsiveness. Thermal sensitivity testing showed a decreased response latency after injury. Without intervention, mechanical and thermal hyper-responsiveness were evident until the end of the experiment (10 weeks). In contrast, treadmill training (2 × 15 min/day; 5 × /week) initiated 6 weeks post-injury resulted in partial amelioration of pain behavior and this effect remained stable. Analysis of calcitonin gene-related peptide (CGRP)-labeled fibers in lamina III-IV of the lumbar dorsal horn revealed an increase in labeling density after SCI. This was not due to changes in the number or size distribution of CGRP-labeled lumbar dorsal root ganglion neurons. Treadmill training reduced the CGRP-labeling density in the spinal cord of injured mice, whereas the density of non-peptidergic isolectin-B4 (IB4)+ fibers showed no changes in lamina IIi and a slight reduction of sparse IB4 labeling in laminae III-IV. Thus, sensorimotor activity initiated in the subchronic/chronic phase of SCI remains effective in ameliorating pain behavior and influencing structural changes of the nociceptive system.