GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation.
Gangliosides are a family of sialic acid-containing glycosphingolipids that are highly enriched in the mammalian nervous system. In particular, b- and c-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to play important roles in adhesion, toxin-binding, neurite extension, cell growth and apoptosis. However, the neurobiological functions of these series of gangliosides remain largely unknown. To clarify the function of b- and c-series gangliosides in pain sensation in vivo, we generated mice in whom the gene for the alpha-2,8-sialyltransferase (GD3 synthase), which is responsible for the generation of all b-series gangliosides as well as c-series gangliosides, was disrupted. Compared to the wild-type mice, the mutant mice exhibited increased sensory responses to thermal and mechanical stimuli as measured by a hot plate test and von Frey test. In contrast, the mutant mice showed decreased responses during the late phase of the formalin test. Paw edema and Fos expression in the spinal cord after formalin injection were significantly decreased in the mutant mice compared to the wild-type mice. No significant differences in the conduction velocity of the sciatic nerve, and no apparent morphologic differences in the spinal cord and the sciatic nerve were detected between the wild-type and the mutant mice. These results suggested that b- and c-series gangliosides are critical in the development and/or maintenance of the sensory nervous system responsible for the transmission of acute pain sensation and pain modulation. Moreover, they play an important role in the development of hyperalgesia induced by inflammation.
Handa
Yoshihiro
Y
Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan Department of Anatomy II, Fukushima Medical College, 1 Hikarigaoka, Fukushima 960-1295, Japan Department of Molecular and Cellular Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Ozaki
Noriyuki
N
Honda
Takashi
T
Furukawa
Koichi
K
Tomita
Yasushi
Y
Inoue
Masahiro
M
Furukawa
Keiko
K
Okada
Masahiko
M
Sugiura
Yasuo
Y
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D005557:Formaldehyde; D005732:Gangliosides / Q000032:analysis; D006358:Hot Temperature; D006930:Hyperalgesia / Q000235:genetics* / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009431:Neural Conduction / Q000502:physiology; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation / Q000009:adverse effects; D011930:Reaction Time / Q000235:genetics; D012584:Sciatic Nerve / Q000503:physiopathology; D012799:Sialyltransferases / Q000172:deficiency* / Q000502:physiology; D012867:Skin / Q000294:innervation / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D005732:Gangliosides; D016761:Oncogene Proteins v-fos; D005557:Formaldehyde; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase