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Romulo Albuquerque, Jooyoung Cho, Bradley Taylor, Jayakrishna Ambati; A novel murine behavioral model of ocular neuropathic pain.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3889. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Neuropathic pain is a complex chronic state arising from injured and dysfunctional nerve tissue that is poorly responsive to analgesic drugs. Neuropathic pain also affects the eye. Ocular neuropathic pain, disguised as ocular surface disease, is often unrecognized and undertreated by clinicians (Rosenthal and Borsook 2015). We tested the hypothesis that alkali burn injury to the ocular surface leads to neuropathic changes in the ocular-trigeminal system and can be used as a molecular and behavioral model to study ocular neuropathic pain.
Wild-type C57Bl6 mice were used. The alkali burn injury model was performed as previously shown (Anderson et al. 2014). Satellite glia activation and neuronal sensitization were studied in the trigeminal ganglia by immunohistochemistry using glial fibrillary acidic protein (GFAP) and neuropeptide-Y (NP-Y). Ocular pain behavior was assessed by eye wiping behavior after application of hypertonic (5M) saline solution to the ocular surface. Ocular pain behavior was tested before and after intra-peritoneal gabapentin (100mg/kg) administration.
Alkali injury to the ocular surface induced expression of GFAP and NP-Y in trigeminal ganglion satellite glial cells and neurons respectively. Alkali injury also increased eye wiping behavior in the injured eye, but not in the contralateral eye up to one week after injury. Increased eye wiping behavior was significantly reduced by treatment with intra-peritoneal gabapentin.
Our model combines two previous ophthalmology models: a surface alkali burn injury to model ocular inflammation (Anderson, Zhou et al. 2014), together with an ocular pain testing involving topical application of hypertonic saline to elicit an eye-wiping response, a behavioral index of pain. Here we show that eye-wiping behavior on the eye ipsilateral but not contralateral to alkali burn was augmented, suggesting sensitization of ocular nociception. These behavior changes were paralleled by increased levels of GFAP and NP-Y in the trigeminal ganglia satellite glial cells and neurons. Eye wiping behavior was abrogated by systemic administration of gabapentin, an antiseizure drug used for the treatment of neuropathic pain. The ability of an analgesic drug like gabapentin to decrease augmented eye wiping suggests that this response is neuropathic in nature and provides a novel model to study the molecular mechanisms of ocular neuropathic pain.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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