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Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture

Abstract

Acupuncture is an invasive procedure commonly used to relieve pain. Acupuncture is practiced worldwide, despite difficulties in reconciling its principles with evidence-based medicine. We found that adenosine, a neuromodulator with anti-nociceptive properties, was released during acupuncture in mice and that its anti-nociceptive actions required adenosine A1 receptor expression. Direct injection of an adenosine A1 receptor agonist replicated the analgesic effect of acupuncture. Inhibition of enzymes involved in adenosine degradation potentiated the acupuncture-elicited increase in adenosine, as well as its anti-nociceptive effect. These observations indicate that adenosine mediates the effects of acupuncture and that interfering with adenosine metabolism may prolong the clinical benefit of acupuncture.

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Figure 1: Acupuncture triggers an increase in the extracellular concentration of ATP, ADP, AMP and adenosine.
Figure 2: Anti-nociceptive effects of adenosine A1 receptors.
Figure 3: Acupuncture fails to suppress pain in mice lacking adenosine A1 receptors.
Figure 4: Pharmacological inhibition of deaminase activity enhances increases in adenosine and prolongs anti-nociception actions of acupuncture.

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Acknowledgements

This work was supported by a grant from the US National Institutes of Health to M.N. and K.T.

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Correspondence to Maiken Nedergaard.

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Goldman, N., Chen, M., Fujita, T. et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci 13, 883–888 (2010). https://doi.org/10.1038/nn.2562

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