Protective effect of adenosine in diabetic neuropathic pain is mediated through adenosine A1-receptors.
Diabetic neuropathic pain is generally considered to be one of the most troublesome complications affecting diabetic patients and current therapy provides inadequate pain relief. In the present study, the effect of adenosine was investigated in a model of diabetic neuropathic pain. Diabetes was induced by streptozotocin (65 mg/kg, ip) in male Sprague Dawley rats and subjected to thermal (cold and hot) and chemical (formalin) stimuli. Diabetic rats developed hyperalgesia by the end of six weeks in thermal and chemical stimuli test. Adenosine (100, 200 and 500 mg/kg, ip) produced significant reversal of responses to thermal and chemical stimuli in diabetic rats. 8-Cyclopentyl-1, 3-dipropylxanthine (DPCPX 1 mg/kg, ip), an adenosine A1-receptor antagonist, but not 3,7-dimethyl-1-propargylxanthine (DMPX 1 mg/kg, ip), an adenosine A2A-receptor antagonist, reversed the protective effect of adenosine. These results indicate that adenosine is an effective analgesics in a model of diabetic neuropathy, and the protection produced by adenosine is via stimulation of adenosine A1-receptors.
Balasubramanyan
Sridhar
S
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160 062, Punjab.
Sharma
Shyam S
SS
D000241:Adenosine / Q000008:administration & dosage / Q000627:therapeutic use*; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004347:Drug Interactions; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D013805:Theobromine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000700:Analgesics; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine