Abstract
To investigate the effects of gabapentin, a structural analog of γ-amino butyric acid (GABA), on the inflammatory response of lipopolysaccharide (LPS)-stimulated rabbit corneal cells (SIRC) and on endotoxin-induced uveitis (EIU) in rabbits. We investigated the LPS-induced expression of several inflammatory mediators, such as TNF-α, IL-1β, cPLA2, COX-2, and PGE2 in the SIRC cells with or without gabapentin treatment. Gabapentin treatment significantly (p < 0.05) attenuated cytokines production, cPLA2 activation, COX-2 expression, and PGE2 levels in SIRC. EIU was induced by an intraocular injection of 0.1 μg of LPS in albino rabbit eye. After 7 and 24 h from LPS injection clinical signs of ocular inflammation were examined by slit lamp with or without topical treatment of 0.5% gabapentin. Tears, aqueous, cornea, conjunctiva, and iris-ciliary body were collected and inflammatory biomarkers assessed. Topical treatment with gabapentin significantly (p < 0.05) reduced clinical signs and biomarkers of inflammation compared with the LPS group both at 7 and 24 h. In conclusion, the results generated in the present study suggest that ophthalmic formulation based on gabapentin may be useful in the treatment of inflammatory conditions associated to ocular pain such as uveitis, and that clinical studies to evaluate this possibility may be warranted.
Highlights
Gabapentin, a structural analog of γ-amino butyric acid (GABA), targeting α2δ1 subunit of voltagesensitive calcium channels, has therapeutic effect for neurological and psychiatric disorders such as epilepsy, anxiety, and neuropathic pain
We investigated the effect of gabapentin both in corneal cells challenging with LPS and in endotoxin-induced uveitis (EIU) assessing the levels of TNF-α, IL-6, IL-1β, and PGE2
MTT assays were carried out in order to assess the effect of gabapentin on stimulated rabbit corneal cells (SIRC) viability (Figure 1). 5, 10, and 100 μg/ml gabapentin did not affect cell viability, either at 24 h or at 48 h
Summary
Gabapentin, a structural analog of γ-amino butyric acid (GABA), targeting α2δ1 subunit of voltagesensitive calcium channels, has therapeutic effect for neurological and psychiatric disorders such as epilepsy, anxiety, and neuropathic pain. This latter is present in the eye and has been reported in patients affected by dry eye disease or diabetes or Sjögren syndrome (Rosenthal et al, 2009). The effect of gabapentin on pain as recently linked to the anti-inflammatory action of the drug. More recently (Dias et al, 2014) it has been showed that gabapentin reverses inflammatory process in well-known acute mouse models of inflammation
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