Laboratory of Georgene Hergenroeder Ph.D.
Dr. Hergenroeder’s primary research interests center on improving patient outcomes after spinal cord and brain injury. Her research focus has been on biomarker discovery in order to predict which patients may benefit from future intervention. For example, identifying factors associated with the development of neuropathic pain after spinal cord injury (SCI).
Neuropathic pain is an adverse consequence of spinal cord injury (SCI) that occurs in 40-70% of patients. The International Association for the Study of Pain (IASP) defines neuropathic pain as “pain caused by a lesion or disease of the somatosensory system”. Neuropathic pain is typically described as “pins & needles”, “burning”, or “pain evoked by light touch”, and can be refractory to conventional treatments. Furthermore, there is concern for misuse and morbidity with opioid agonists. Unmitigated pain limits physical activity, negatively impacts rehabilitation, infringes on work and social activities, and reduces quality of life. Experimental studies using rodent models of SCI have identified multiple mechanisms that may contribute to the development of neuropathic pain. For example, damage to nociceptive primary afferents, enhanced excitability of nociceptors, and chronic disruption of the blood-spinal cord barrier (BSCB) have been proposed as potential mechanisms. Although these studies are beginning to provide a cellular and molecular basis for neuropathic pain, there is currently no distinguishing characteristic or biomarker available to identify SCI patients that are at elevated risk for developing this condition. Early identification may lead to treatments for prevention of neuropathic pain.
SCI-induced disruption of the BSCB can allow the immune system to elicit an IgG response against central nervous system proteins. Using 2-D gel electrophoresis and western blotting approaches, we detected enhanced immunoreactivity in patients’ plasma 16 ± 7d after SCI and confirmed these findings in an expanded cohort. Mass spectrometry identified glial fibrillary acidic protein (GFAP) and collapsin response mediator protein 2 (CRMP2) as two potential autoantigens. Additional assays determined that in acute SCI, 63% SCI subjects were positive for one or both autoantibodies. The presence of autoantibodies to GFAP and/or CRMP2 in patient plasma at 16 ± 7d after SCI increased the odds of developing neuropathic pain within 6 months of injury by 9.5 times (p=0.006).
Ongoing studies aim to determine whether there is a causal relationship between the presence of GFAP antibodies and pain-like behaviors and spinal cord tissue pathology using a model system. Future work aims to identify additional autoantibodies contributing to neuropathic pain.
TEAM MEMBERS
- Samuel Molina, BS
- Elton Oliveira, BS
- Lisa Schmitt, BSN