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Supraspinal sensory perception after spinal cord injury and the modulatory factors associated with below-level allodynia
2009
Abstract
Spinal cord injury (SCI) impairs sensory systems causing debilitating chronic allodynia, neuropathic pain elicited from an innocuous stimulus. While inflammation can cause allodynia under some conditions, no ameliorative cure exists. Our rat spinal cord contusion model emulates the pathology of human SCI but its validity as a model of allodynia remains debatable. Hence, our goals were: to validate and extend behavioral assessments of below-level allodynia for experimental SCI, to identify the anatomical and functional connections involved in processing sensation after SCI, and to characterize the patterns of glial activation and pro-inflammatory cytokine production in sensory processing centers of the lumbar spinal cord. To test for allodynia in experimental SCI, we validated current paradigms and developed a new assessment of sensation that did not rely on hindlimb or postural control. We validated these techniques in >150 rats with SCI and demonstrate that Up-Down methods provide a quantitative assessment of perceptual threshold. With the new sensory test, thresholds collected prior to recovery of hindlimb weight support predicted chronic thresholds with 75-89% accuracy. Subsequently, we showed that anatomical connections between L5 and supraspinal centers remain intact after moderate SCI. Mechanistically, the activation of microglia and p38 MAP kinase in L5 cord predicted allodynia. Tumor necrosis factor-a and interluekin-1b, increased in the L5 dorsal horn by 7 dpo and interleukin-6 was elevated chronically. These data suggest that remote microglial activation is pivotal in SCI-induced allodynia. Fractalkine, a microglial activator, and astrocytes were not primary modulators of pain. Finally, we showed supraspinal processing of below-level stimuli occurs after moderate SCI using functional MRI and somatosensory evoked potentials (SSEP). SSEPs delineated pain-specific delays in S1 cortical depolarization. Importantly, we show that fMRI captures cortical activation in the rat brain elicited by the same noxious pinprick stimulus used in clinical practice to classify below-level sensation in people. Taken together, the behavioral, perceptual, and inflammatory markers of below-level allodynia established in this dissertation define a profile of SCI-induced allodynia that can be applied to differentiate and diagnose below-level allodynia in the laboratory and the clinic.
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Details
- Title
- Supraspinal sensory perception after spinal cord injury and the modulatory factors associated with below-level allodynia
- Creators
- Megan Detloff - The Ohio State University
- Publisher
- Ohio State University
- Resource Type
- Book
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Other Identifier
- 9781109660975; 1109660979; 991020111299404721