Gangliosides are abundant in neural tissue and play important roles in cell-cell adhesion, signal transduction, and cell differentiation.
Gangliosides are divided into 4 groups: asialo-, a-, b-, and c-series
gangliosides, based on their biosynthetic pathway. St8sia1 knockout mice, which lack b- and c-series
gangliosides, exhibit altered nociceptive responses. The mechanism underlying this defect, however, remains unclear. To address this issue, we first investigated the possibility that
gangliosides in peripheral nociceptor endings are involved in nociception. Intraplantar injection of the b-series
ganglioside GT1b, but not a-series
gangliosides such as GM1, produced nociceptive responses and enhanced low-concentration
formalin-induced nociception.
N-methyl-d-aspartic acid receptor and type I
metabotropic glutamate receptor antagonists inhibited GT1b-induced
hyperalgesia, suggesting the involvement of
glutamate receptors. Furthermore, microdialysis analysis revealed elevated
glutamate content in subdermal tissues due to intraplantar injection of GT1b. Co-injection of
glutamate dehydrogenase with GT1b attenuated GT1b-induced
hyperalgesia. These findings suggested that GT1b induced extracellular
glutamate to accumulate in subdermal tissues, thereafter activating
glutamate receptors, which in turn resulted in
hyperalgesia and nociception. On the other hand, intraplantar injection of
sialidase, which cleaves sialyl residues from
glycoconjugates such as
gangliosides, attenuated the late phase of 2%
formalin-induced nociception. Thus, the antinociceptive effects of
sialidase and the nociceptive effects of GT1b indicated that endogenous
gangliosides are involved in nociceptive responses. These results suggest that
gangliosides play important roles in nociceptive responses originating in peripheral nociceptor endings.
Ganglioside GT1b induced extracellular
glutamate to accumulate in subdermal tissues, thereafter activating
glutamate receptors, which in turn resulted in
hyperalgesia and nociception.