Modulation of P2X receptors in dorsal root ganglion neurons of streptozotocin-induced diabetic neuropathy.
Painful diabetic neuropathy causes hyperalgesia and does not respond to commonly used analgesics such as non-steroidal anti-inflammatory drugs or opioids at doses below those producing disruptive side effects. In the present study, we examined the effect of P2X receptor antagonists, which are known to modulate the pain pathway, on mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic mice. The paw withdrawal frequency measured by von Frey filaments, began to significantly increase 5 days after STZ injection and was maintained for more than 14 days. Intrathecal administration of P2X receptor antagonists (PPADS and TNP-ATP) inhibited the mechanical allodynia in diabetic mice. The levels of P2X(2) and P2X(3) receptors mRNA were significantly increased in diabetic mice at 14 days after the intravenous injection of STZ. These results suggest that the upregulation of P2X(2), P2X(3) and/or P2X(2/3) receptor in DRG neurons is associated with mechanical allodynia in STZ-induced diabetic mice.
Migita
Keisuke
K
Department of Neurophysiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Moriyama
Tomoko
T
Koguchi
Masako
M
Honda
Kenji
K
Katsuragi
Takeshi
T
Takano
Yukio
Y
Ueno
Shinya
S
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000378:metabolism* / Q000473:pathology; D010147:Pain Measurement; D010812:Physical Stimulation; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C546402:P2rx2 protein, mouse; C546409:P2rx3 protein, mouse; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate