Supraspinal Sensory Perception after Spinal Cord Injury and the Modulatory Factors Associated with Below-Level Allodynia
Year: 2009
Type: article
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 iii 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-α and interluekin-1β 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 belowlevel 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.iv ACKNOWLEDGEMENTS At an early age, my parents inspired me to be creative and imaginative, while still maintaining that I be diligent and devoted in my endeavors.Emails and phone calls always end in the same way: "Be safe, eat healthy, work hard and have fun, Love, Mom and Dad."It has been a challenge during graduate school to find the balance between "working hard" and "having fun," but now that I'm almost finished, I think I might be onto something… Acknowledgements for working hard: So many people have been involved in making my little projects successful.The wisdom and support of the technicians, peers, and mentors in the Center for Brain and Spinal Cord Repair Laboratories will never be forgotten.Veterinarians Drs.Valerie Bergdall, Judy Hickman-Davis, Carrie Freed and Stephanie Lewis were integral in the development of new experimental techniques, and the health and welfare of the animals used throughout these studies.I would also like to thank Herbert Douce of Respiratory Therapy and Allison Spiwak of Circulation Technology for their knowledge of how to keep breathing.I would also like to thank John Buford for stepping in at the last minute and collecting SSEPs.Our "fallback" plan appears to have worked out.
Author: Megan Ryan Detloff
Institution: The Ohio State University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2488549497