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

Authors
 Kui Y. Yang  ;  Jun H. Mun  ;  Ki D. Park  ;  Min J. Kim  ;  Jin S. Ju  ;  Seong T. Kim  ;  Yong C. Bae  ;  Dong K. Ahn 
Citation
 PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, Vol.57 : 100-109, 2015 
Journal Title
 PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY 
ISSN
 0278-5846 
Issue Date
2015
MeSH
Amino Acid Transport System X-AG/antagonists & inhibitors* ; Animals ; Aspartic Acid/administration & dosage ; Aspartic Acid/pharmacology* ; Aspartic Acid/therapeutic use ; Astrocytes/drug effects ; Botulinum Toxins, Type A/pharmacology ; Facial Pain/drug therapy* ; Freund's Adjuvant/antagonists & inhibitors ; Freund's Adjuvant/pharmacology ; Glutamate-Ammonia Ligase/antagonists & inhibitors ; Glutamic Acid/metabolism* ; Hyperalgesia/chemically induced ; Hyperalgesia/drug therapy* ; Injections, Intraventricular ; Interleukin-1beta/antagonists & inhibitors ; Interleukin-1beta/pharmacology ; Male ; Methionine Sulfoximine/administration & dosage ; Methionine Sulfoximine/pharmacology* ; Methionine Sulfoximine/therapeutic use ; Nociception/drug effects* ; Rats ; Spinal Cord Dorsal Horn/drug effects ; Spinal Cord Dorsal Horn/physiology
Keywords
Glutamate ; Glutamate transporter ; Glutamine synthetase inhibitor ; Orofacial pain ; Paradoxical antinociception
Abstract
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 (10 μg) 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, intracisternal injection of MSO blocked the up-regulation of c-Fos immunoreactivity in CFA-treated rats only. We also investigated the effects of botulinum toxin type A (BoNT-A) on TBOA-induced paradoxical antinociception in CFA-treated rats, as BoNT-A inhibits the release of neurotransmitters, including glutamate. BoNT-A treatment reversed behavioral responses produced by intracisternal administration of TBOA in CFA-treated rats. These results suggest that the paradoxical responses produced by blocking glutamate transporters under inflammatory pain conditions are mediated by the modulation of glutamate release from presynaptic terminals. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic inflammatory pain conditions.
Full Text
http://www.sciencedirect.com/science/article/pii/S0278584614002024
DOI
10.1016/j.pnpbp.2014.10.011
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Orofacial Pain and Oral Medicine (구강내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seong Taek(김성택)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/157143
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