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.

The role of miR-190a-5p contributes to diabetic neuropathic pain via targeting SLC17A6

“… 27 , 28 Finally, Chicago Sky Blue 6B (CSB6B) selectively inhibited the function of VGLUTs and was reported to weaken inflammatory pain in related mouse model. 29 , 30 In this study, the results showed that when miR-190a-5p was upregulated, SLC17A6 was downregulated, IL-1β and IL-6 were decreased in lumbar spinal dorsal horn, and painful behavior was improved. In addition, when SLC17A6 was inhibited, IL-1β and IL-6 were also decreased in lumbar spinal dorsal horn, and pain behavior was also improved.…”

Antinociceptive effects of incarvillateine, a monoterpene alkaloid from Incarvillea sinensis and possible involvement of the adenosine system

“…The antinociceptive effects of incarvillateine were initially assessed using the acetic acid-induced writhing test as described previously 46 . Briefly, mice were i.p.…”

“…The hot plate test was performed as described previously 46 . Mice were individually placed on the surface of a hot plate (HUGO SACHS Elektronik-Harvard Apparatus GmbH, March-Hugstetten, Germany) maintained at 55 ± 0.5 °C.…”

The small molecule Chicago Sky Blue promotes heart repair following myocardial infarction in mice

“…We validated these results using a different echocardiography system (Supplemental Figure 1, A and B). Previous studies showed that CSB has several biological effects (37,(42)(43)(44)(45)(46). Therefore, we examined the mice for adverse side effects at the end of the in vivo experiment, 21 days after MI.…”

“…CSB was shown to have several biological targets, including VGLUT (46), MIF (38), CaMKP (62), RAD51 (39), ubiquitin (40), and the Prion protein (63). In vivo, CSB was shown to attenuate methamphetamine-induced hyperac- tivity (46), to have antinociceptive effects (44), to attenuate secondary injuries in the spinal cord (45), and to modulate feeding in broilers (42).…”