The antinociceptive effect of 2-chloro-2'-C-methyl-N6-cyclopentyladenosine (2'-Me-CCPA), a highly selective adenosine A1 receptor agonist, in the rat.
This study was undertaken in order to investigate the effect of 2-chloro-2'-C-methyl-N(6)-cyclopentyladenosine (2'-Me-CCPA), a potent and highly selective adenosine A(1) receptor agonist, on nociceptive responses and on the ongoing or tail flick-related changes of rostral ventromedial medulla (RVM) ON- and OFF-cell activities. Systemic administrations of 2'-Me-CCPA (2.5-5 mg/kg, i.p.) reduced the nociceptive response in the plantar and formalin tests, in a way prevented by DPCPX (3 mg/kg, i.p.), a selective A(1) receptor antagonist. Similarly, intra-periaqueductal grey (PAG) 2'-Me-CCPA (0.5-1-2 nmol/rat) reduced pain behaviour in the plantar and formalin tests, in a way inhibited by DPCPX (0.5 nmol/rat). Moreover, when administered systemically (2.5-5 mg/kg, i.p.) or intra-PAG (0.5-1 nmol/rat) 2'-Me-CCPA increased the tail flick latencies, delayed the tail flick-related onset of the ON-cell burst and decreased the duration of the OFF-cell pause in a dose dependent manner. Furthermore, it decreased RVM ON-cell and increased OFF-cell ongoing activities. The in vivo electrophysiological effects were all prevented by DPCPX (0.5 nmol/rat). This study confirms the role of adenosine A(1) receptors in modulating pain and suggests a critical involvement of these receptors within PAG-RVM descending pathway for the processing of pain.
Maione
S
S
Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy Department of Chemical Sciences, University of Camerino, 62032 Camerino, Italy.
de Novellis
V
V
Cappellacci
L
L
Palazzo
E
E
Vita
D
D
Luongo
L
L
Stella
L
L
Franchetti
P
P
Marabese
I
I
Rossi
F
F
Grifantini
M
M
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058907:Adenosine A1 Receptor Agonists; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D058907:Adenosine A1 Receptor Agonists; D000700:Analgesics; C058394:2-chloro-N(6)cyclopentyladenosine; D000241:Adenosine