Blockade of spinal glutamate recycling produces paradoxical antinociception in rats with orofacial inflammatory pain

Publication date: 3 March 2015 Source:Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 57 Author(s): Kui Y. Yang , Jun H. Mun , Ki D. Park , Min J. Kim , Jin S. Ju , Seong T. Kim , Yong C. Bae , Dong K. Ahn In our current study, we investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain. DL-threo-β-benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block spinal glutamate transporter and glutamine synthetase activity in astroglia. Intracisternal administration of high dose TBOA (10μg) produced thermal hyperalgesia in naïve rats but significantly attenuated the thermal hyperalgesia in rats that had been pretreated with interleukin (IL)-1β or Complete Freund's Adjuvant (CFA). In contrast, intracisternal injection of MSO produced anti-hyperalgesic effects against thermal stimuli in CFA-treated rats only. To confirm the paradoxical antinociceptive effects of TBOA and MSO, we examined changes in c-Fos expression in the medullary dorsal horn produced by thermal stimulation in naïve, IL-1β-, or CFA-treated rats, after intracisternal injections of TBOA and MSO. Intracisternal administration of TBOA significantly increased c-Fos immunoreactivity in naïve rats. In contrast, intracisternal administration of TBOA significantly decreased the up-regulation of c-Fos immunoreactivity in the medullary dorsal horn of IL-1β- and CFA-treated rats. However, intraciste...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research