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Adenosine receptor activation and nociception
Adenosine and ATP exert multiple influences on pain transmission at peripheral and spinal sites. At peripheral nerve terminals in rodents, adenosine A 1 receptor activation produces antinociception by decreasing, while adenosine A 2 receptor activation produces pronociceptive or pain enhancing prope...
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Published in: | European Journal of Pharmacology 1998-04, Vol.347 (1), p.1-11 |
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Main Author: | |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Adenosine and ATP exert multiple influences on pain transmission at peripheral and spinal sites. At peripheral nerve terminals in rodents, adenosine A
1 receptor activation produces antinociception by decreasing, while adenosine A
2 receptor activation produces pronociceptive or pain enhancing properties by increasing, cyclic AMP levels in the sensory nerve terminal. Adenosine A
3 receptor activation produces pain behaviours due to the release of histamine and 5-hydroxytryptamine from mast cells and subsequent actions on the sensory nerve terminal. In humans, the peripheral administration of adenosine produces pain responses resembling that generated under ischemic conditions and the local release of adenosine may contribute to ischemic pain. In the spinal cord, adenosine A
1 receptor activation produces antinociceptive properties in acute nociceptive, inflammatory and neuropathic pain tests. This is seen at doses lower than those which produce motor effects. Antinociception results from the inhibition of intrinsic neurons by an increase in K
+ conductance and presynaptic inhibition of sensory nerve terminals to inhibit the release of substance P and perhaps glutamate. There are observations suggesting some involvement of spinal adenosine A
2 receptors in pain processing, but no data on any adenosine A
3 receptor involvement. Endogenous adenosine systems contribute to antinociceptive properties of caffeine, opioids, noradrenaline, 5-hydroxytryptamine, tricyclic antidepressants and transcutaneous electrical nerve stimulation. Purinergic systems exhibit a significant potential for development as therapeutic agents. An understanding of the contribution of adenosine to pain processing is important for understanding how caffeine produces adjuvant analgesic properties in some situations, but might interfere with the optimal benefit to be derived from others. |
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ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/S0014-2999(97)01605-1 |