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-N6-cyclopentyladenosine (2′-Me-CCPA), a potent and highly selective adenosine A1 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 A1 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 A1 receptors in modulating pain and suggests a critical involvement of these receptors within PAG–RVM descending pathway for the processing of pain.