Adenosine as a potential analgesic target in inflammatory and neuropathic pains

Ah. Dickenson et al., Adenosine as a potential analgesic target in inflammatory and neuropathic pains, CNS DRUGS, 13(2), 2000, pp. 77-85
Citations number
Categorie Soggetti
Pharmacology,"Neurosciences & Behavoir
Journal title
ISSN journal
1172-7047 → ACNP
Year of publication
77 - 85
SICI code
Substantial evidence exists for the physiological role of adenosine in the modulation of primary afferent transmission. Since the first description of the antinociceptive effects of adenosine, there has been considerable inte rest in the development of adenosine analogues as potential analgesics for the treatment of various pain states. The direction of effect of adenosine in the periphery is complicated by the existence of multiple receptors and species differences. The analgesic actions of agents acting on adenosine re ceptor systems are largely attributed to actions at the spinal cord. Two su btypes of adenosine receptors (A(1) and A(2)) have been identified in the s ubstantia gelatinosa of the spinal cord where they were shown to be localis ed primarily on intrinsic neurons. Although evidence exists for the involve ment of A(2) receptors in spinally mediated antinociception, it appears to be predominantly the A(1) receptor subtype which plays a major role in inhi biting the nociceptive input in the dorsal spinal cord. The antinociceptive properties of adenosine and receptor-selective analogue s have been demonstrated across a wide range of animal models, including ac ute nociceptive tests and in models of inflammation and neuropathy. These r esults, observed across several models of pain, strongly support the potent ial clinical use of these agents in various pain states. In humans, systemi c or intrathecal administration of adenosine was shown to be effective agai nst experimentally induced pain in healthy volunteers. Subsequently, there is evidence for the effectiveness of systemic and spinally administered ade nosine in patients with neuropathic pain. A number of studies have demonstrated possible interactions between adenosi ne and glutamate in the spinal cord, and between N-methyl-D-aspartate recep tor activation and adenosine release elsewhere in the brain. There is also some evidence that drugs acting to inhibit the metabolism of adenosine may have therapeutic potential in pain states. In this context, the release of adenosine appears to be elevated in hyperexcitable neuronal systems. This w ould allow therapies to selectively target active neurons in pain systems a nd therefore would be expected to have low adverse effect liability.