Characterization of the antinociceptive effects of some adenosine analogues in the rat

Abstract

The antinociceptive effects of the stable adenosine analogues N6-phenylisopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamidoadenosine (NECA) were investigated in conscious rats using cutaneous thermal tests (hot plate and tail flick). Subcutaneous administration of the adenosine analogues induced a dose-dependent antinociceptive response for all agents. However, NECA was approximately 15 times more potent than PIA and CHA. Approximately the same potency order and response was seen when the adenosine analogues were administered intrathecally at the lumbar level. By this route of administration, the adenosine analogues were approximately 10-20 times more potent than after S.C. administration. Intracerebroventricular administration (lateral ventricles), however, induced a variable response, in most cases a slight hyperalgesia. The nonspecific adenosine antagonist theophylline (S.C.) rapidly reduced the antinociceptive effect induced by PIA (S.C.) but enprofylline, a bronchodilating xanthine with low ability to antagonize adenosine did not influence PIA-induced antinociception. It is concluded that stable adenosine analogues and presumably adenosine itself have potent antinociceptive effects via specific adenosine receptors in the rat. The effects seem to be mediated mainly by a spinal mechanism of action.

Adenosine modulates excitatory synaptic transmission and suppresses neuronal death induced by ischaemia in rat spinal motoneurones

“…It is well known that adenosine regulates pain transmission at the level of the spinal cord, particularly by activating A 1 receptors. Intrathecal adenosine analogues or A 1 receptor agonists produce antinociception in behavioural studies [20,46]. Consistent with this, electrophysiological studies have demonstrated that adenosine directly hyperpolarises dorsal horn neurones [26,41] and inhibits glutamatergic transmission in the dorsal horn through activation of presynaptic A 1 receptors [22,23,41].…”

Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice

“…A 2B and A 3 receptors are widely distributed, but are present at a low density in the central nervous system (Feoktistov and Biaggioni, 1997;Rivkees et al, 2000). Within the spinal cord adenosine acts to suppress nociceptive signalling, mediated via the A 1 receptor (DeLander and Hopkins, 1986;Holmgren et al, 1986), while in the periphery it has an algogenic activity which may be mediated via an A 2 receptor subtype (McQueen and Ribeiro, 1986; see Sawynok and Yaksh, 1993). In the mouse the location of these receptors are most probably on sensory nerves as there is no A 2A receptor binding in the spinal cord (Bailey et al, 2002b;Kelly et al, 2004).…”

Antinociceptive Effects of Novel A2B Adenosine Receptor Antagonists

“…The role of adenosine receptors in nociception is complex and may involve different mechanisms in the central nervous system and in peripheral tissues. For example, spinal administration of adenosine receptor agonists produces antinociception in a variety of animal models of pain, presumably through the activation of spinal A 1 and to a lesser extent through A 2 receptors (Holmgren et al, 1986;Sawynok, 1998). Adenosine can produce analgesic or pronociceptive effects (Doak and Sawynok, 1995) through the activation of peripheral A 1 and A 2 receptors, respectively (Taiwo and Levine, 1990;Doak and Sawynok, 1995).…”