Differential effects of adenosine A1 receptor on pain-related behavior in normal and nerve-injured rats.
This study investigated the effects of N6-cyclopentyladenosine (CPA), a potent and selective adenosine A1 receptor (A1R) agonist in normal and nerve-injured rats and mechanisms of its action by behavioral tests and electrophysiological technique. The results showed: (1) In normal rats, intraperitoneal administration of CPA (1mg/kg) increased paw withdrawal latencies, in a way blocked by a selective A1R antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, 3mg/kg, i.p.), but had no influence on the threshold of mechanical stimulation. (2) In rats with neuropathic pain induced by spinal nerve ligation (SNL), CPA reduced thermal hyperalgesia and mechanical allodynia, which could last 6h and 10h, respectively (n=6/group, P<0.05). Both of the effects could be blocked by pretreatment of DPCPX intraperitoneally. (3) The baseline of C-fiber but not A-fiber evoked field potentials was depressed by spinal application of CPA (0.01 mM), and this effect was prevented by application of DPCPX (0.02 mM) 30 min before CPA. (4) Spinal application of CPA depressed long-term potentiation (LTP) of A- and C-fiber evoked field potentials, and both the depression could be blocked by pretreatment of DPCPX 30 min before CPA. These results suggested that the activation of A1R has different influences on normal and neuropathic rats probably due to the absence and presence of central sensitization in spinal dorsal horn.
Gong
Qing-Juan
QJ
Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yat-Sen University, 74 Zhongshan Rd 2, Guangzhou 510080, China.
Li
Yu-Ying
YY
Xin
Wen-Jun
WJ
Wei
Xu-Hong
XH
Cui
Yue
Y
Wang
Jun
J
Liu
Yong
Y
Liu
Cui-Cui
CC
Li
Yong-Yong
YY
Liu
Xian-Guo
XG
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000379:methods; D004594:Electrophysiology; D004924:Escape Reaction / Q000187:drug effects; D007274:Injections, Intraperitoneal; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology*
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine