title: The antinociceptive effects of intracerebroventricular administration of Chicago sky blue 6B, a vesicular glutamate transporter inhibitor.
abstract: Accumulating evidence suggests that vesicular glutamate transporters (VGLUTs), which control the storage and release of glutamate, may play a role in pain processing. Chicago sky blue 6B (CSB6B), which is structurally related to glutamate, is a competitive VGLUT inhibitor without affecting plasma membrane transporters. The present study was designed to investigate the antinociceptive effects of CSB6B in a number of pain models. The hot-plate test was used as an acute thermal pain test. Inflammatory pain was evaluated using acetic acid writhing, formalin, and complete Freund's adjuvant tests. Intracerebroventricular administration of CSB6B did not affect acute thermal pain responses in 50 or 55°C hot plate tests. However, CSB6B attenuated acetic acid-induced writhing in a dose-dependent and time-dependent manner. In addition, CSB6B reduced licking/biting behavior during the second phase, but not during the first phase, following an intraplantar injection of formalin. In the complete Freund's adjuvant test, a significant attenuation of thermal hyperalgesia was also observed in CSB6B-treated mice. At antinociceptive doses, CSB6B did not affect mice spontaneous locomotor activity. The present study shows that pharmacological inhibition of VGLUT activity was sufficient to attenuate experimental inflammatory pain and suggests that regulation of VGLUTs might be a novel therapeutic strategy for the treatment of pain.
authors.affiliation: aBeijing Institute of Pharmacology and Toxicology, Beijing bFaculty of Life Science and Technology, Kunming University of Science and Technology, Kunming cGuangxi Medical University, Nanning, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.forename: Shoupu
authors.initials: S
authors.lastname: Yi
authors.forename: Meiliang
authors.initials: M
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: Lingdi
authors.initials: L
authors.lastname: Yan
authors.forename: Ruibin
authors.initials: R
authors.lastname: Su
authors.forename: Zehui
authors.initials: Z
authors.lastname: Gong
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects*; D014343:Trypan Blue / Q000008:administration & dosage* / Q000494:pharmacology*; D050496:Vesicular Glutamate Transport Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D050496:Vesicular Glutamate Transport Proteins; C009000:pontamine sky blue; D014343:Trypan Blue