Pricking Out Pain with Adenosine

Sci. Signal.  13 Jul 2010:
Vol. 3, Issue 130, pp. ec209
DOI: 10.1126/scisignal.3130ec209

Acupuncture is an ancient procedure involving the insertion of needles that are rotated, heated, or electrically stimulated to relieve pain (see Zylka). Goldman et al. found that acupuncture at the "Zusanli" point (near the knee) in mice produced nociception and increased the local concentrations of adenine nucleotides (ATP, ADP, and AMP) and adenosine. Whereas the extracellular concentration of ATP rapidly returned to baseline after a 30-minute acupuncture session, ADP, AMP, and adenosine concentrations remained increased 1 hour after the session. Adenosine has antinociceptive properties mediated by the A1 receptor (A1R). Injection of an A1R agonist at the Zusanli point also reduced pain in two different pain models, and acupuncture and the A1R agonist were ineffective in reducing pain in mice deficient for A1R. By recording in vivo responses of the anterior cingulated cortex, which is the region of the brain that receives pain signals from the foot, Goldman et al. showed that acupuncture or the A1R agonist of the ipsilateral leg both reduced the amplitude of field excitatory postsynaptic potentials in response to painful foot shock. In contrast, treatment of the contralateral leg failed to reduce the activity of this region of the brain in response to painful foot shock. Systemic inhibition of both AMP deaminase and adenosine deaminase, enzymes that metabolize these molecules, with deoxycoformycin (a clinically approved anticancer drug) prolonged the duration that local AMP and adenosine concentrations remained increased after acupuncture and enhanced the duration of the pain-relieving effects of acupuncture. This work provides a mechanism for the basis of acupuncture, as well as indicates that combining acupuncture with pharmacological inhibition of adenosine metabolism may expand the types of pain that acupuncture can alleviate.

N. Goldman, M. Chen, T. Fujita, Q. Xu, W. Peng, W. Liu, T. K. Jensen, Y. Pei, F. Wang, X. Han, J.-F. Chen, J. Schnermann, T. Takano, L. Bekar, K. Tieu, M. Nedergaard, Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat. Neurosci. 13, 883–888 (2010). [PubMed]

M. J. Zylka, Needling adenosine receptor for pain relief. Nat. Neurosci. 13, 783–784 (2010). [PubMed]