Comprehensive Analysis of the GABAergic System Gene Expression Profile in the Anterior Cingulate Cortex of Mice With Paclitaxel-Induced Neuropathic Pain
The supraspinal pathophysiology of the painful neuropathy induced by paclitaxel, a chemotherapeutic agent, is not well understood. The γ-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of neuropathic pain. Gene expression of GABAergic system molecules was examined in the anterior cingulate cortex (ACC) of mice brains, by real-time PCR, during paclitaxel-induced neuropathic pain, because this area is involved in pain perception and modulation that might contribute to neuropathic pain. Paclitaxel treatment resulted in thermal hyperalgesia and in increased GABA transporter-1 (GAT-1) mRNA expression, but not that of other GABA transporters or GABAergic enzymes in the ACC compared to vehicle treatment. Among the 18 GABAA receptor subunits analyzed, only β2, β3, δ, and γ2 had increased mRNA levels, and for the GABAB receptor subunit, only GABAB2 had increased mRNA levels in the ACC of paclitaxel-treated mice, whereas the rest of the GABA receptor subunits were not altered. The mRNA expression of GABAA receptor subunits α6, , π, ρ1, ρ2, and ρ3 were not detected in the ACC. In conclusion, these data show that during paclitaxel-induced neuropathic pain there is significant increase in GAT-1 expression in the ACC. GAT-1 is the main transporter of GABA from the synapse, and thus its increased expression possibly results in less GABA at the synapse and dysregulation of the GABAergic system. GAT-1 is a potential therapeutic target for managing paclitaxel-induced neuropathic pain.
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Document Type: Research Article
Affiliations: Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait
Publication date: February 20, 2015
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