Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / pharmacology
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Animals
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Diabetes Mellitus, Experimental / complications
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Diabetes Mellitus, Experimental / metabolism*
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Diabetes Mellitus, Experimental / physiopathology
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Diabetic Neuropathies / metabolism*
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Diabetic Neuropathies / physiopathology
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Disease Models, Animal
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Ganglia, Spinal / metabolism*
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Hyperalgesia / etiology
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Hyperalgesia / metabolism
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Hyperalgesia / physiopathology
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Male
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Mice
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Nociceptors / metabolism*
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Nociceptors / pathology
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Pain Measurement
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Physical Stimulation
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Platelet Aggregation Inhibitors
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Purinergic P2 Receptor Antagonists
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Pyridoxal Phosphate / analogs & derivatives
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Pyridoxal Phosphate / pharmacology
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Receptors, Purinergic P2 / genetics
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Receptors, Purinergic P2 / metabolism*
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Receptors, Purinergic P2X2
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Receptors, Purinergic P2X3
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Sensory Receptor Cells / metabolism*
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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P2rx2 protein, mouse
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P2rx3 protein, mouse
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Platelet Aggregation Inhibitors
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Purinergic P2 Receptor Antagonists
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RNA, Messenger
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Receptors, Purinergic P2
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Receptors, Purinergic P2X2
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Receptors, Purinergic P2X3
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pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid
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Pyridoxal Phosphate
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2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate
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Adenosine Triphosphate