Administration of anti-GFAP antibodies increases CGRP expression and increases pain hypersensitivity in spinal cord injured animals.

Background: Spinal cord injury (SCI) results in a multitude of cellular and pathological changes including neuronal loss, axonal damage, gliosis, and loss of motor and sensory function. In 40%-70% of patients, SCI can also trigger the development of neuropathic pain. Our previous study demonstrated that SCI patients who developed autoantibodies to glial fibrillary acidic protein (GFAP) were at increased risk for the subsequent development of neuropathic pain. However, whether GFAP autoantibodies (GFAPab) contribute to the development of neuropathic pain after SCI had yet to be examined.

Objective: Using a mid-thoracic contusion model of SCI in male Sprague-Dawley rats, we examined the effect of exogenous anti-GFAP antibodies on SCI pathology, pain-associated molecular changes, and behavior.

Methods: Anti-GFAP or IgG was administered at 7- and 14-days post-injury. Immunohistochemistry was performed to measure the relative levels of calcitonin gene-related peptide (CGRP), and inflammatory proteins in dorsal horn tissue. To assess the development of neuropathic pain, the von Frey test and the Mechanical Conflict-Avoidance Paradigm (MCAP) were performed.

Results: CGRP immunoreactivity was significantly higher in the anti-GFAP-treated injured rats compared to control SCI IgG-treated rats. As anticipated, SCI rats had a lower pain threshold at 1- and 2-months post-injury compared to laminectomy-only controls. However, pain withdrawal threshold was not significantly affected by post-injury administration of the anti-GFAP. Operant testing revealed that SCI rats treated with the anti-GFAP had a trending increase in pain sensitivity.

Conclusion: Taken together, these data suggest that autoantibodies to GFAP following SCI may contribute to developing pain states following SCI.