Upregulations of P2X(3) and ASIC3 involve in hyperalgesia induced by cisplatin administration in rats.
The role of ion channels expressed in sensory neurons on mechanical and thermal hyperalgesia was examined in a rat model of cisplatin-induced peripheral neuropathy. The rats were injected with 3mg/kg of cisplatin intraperitoneally once per week for five consecutive weeks. The von Frey test, pin-prick test and plantar test were performed to examine any noxious sensitivity of the skin. The Randall-Selitto test of the gastrocnemius muscle (GM) and the measurement of grip forces were performed to quantify muscle hyperalgesia. Coordination/motor was assessed by Rota-rod testing. Expressions of the ion channels TRPV1, TRPV2, P2X(3) and ASIC3 were examined in dorsal root ganglion (DRG) neurons and the muscle afferent neurons innervating GM. Effects of antagonists against either P2X(3) or ASICs on behavioral responses were evaluated. Mechanical hyperalgesia and allodynia of both skin and muscle were observed in cisplatin-treated animals. Expressions of TRPV2, P2X(3), and ASIC3 increased in all DRG neurons. In addition, expressions of P2X(3) and ASIC3 also increased in muscle afferent neurons in DRGs. Antagonists against P2X(3,2/3) and ASICs showed a suppressive effect on both skin and muscle hyperalgesia induced by cisplatin administration. Upregulation of TRPV2, P2X(3), and ASIC3 may play important roles in the mechanical hyperalgesia induced by cisplatin. Furthermore, cisplatin treatment also induced muscle hyperalgesia in muscle afferent neurons in connection with the upregulation of P2X(3) and ASIC3.
Hori
Kiyomi
K
Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan Department of Rehabilitation, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan Department of Anatomy and Neuroembryology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan Program in Physical and Occupational Therapy, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya 461-8673, Japan.
Ozaki
Noriyuki
N
Suzuki
Shigeyuki
S
Sugiura
Yasuo
Y
D062565:Acid Sensing Ion Channels; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism; D058477:Receptors, Purinergic P2X3; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000294:innervation / Q000503:physiopathology; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D000970:Antineoplastic Agents; D009419:Nerve Tissue Proteins; C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C476722:Trpv2 protein, rat; D002945:Cisplatin