Adenosine A1 Receptors Mediate Local Anti-nociceptive Effects of Acupuncture

Overview

Journal Nat Neurosci

Date 2010 Jun 1

PMID 20512135

Citations 355

Authors

Nanna Goldman

Michael Chen

Takumi Fujita

Qiwu Xu

Weiguo Peng

Wei Liu

Tina K Jensen

Yong Pei

Fushun Wang

Xiaoning Han

Jiang-Fan Chen

Jurgen Schnermann

Takahiro Takano

Lane Bekar

Kim Tieu

Maiken Nedergaard

Affiliations

Soon will be listed here.

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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References

Castrop H, Huang Y, Hashimoto S, Mizel D, Hansen P, Theilig F . Impairment of tubuloglomerular feedback regulation of GFR in ecto-5'-nucleotidase/CD73-deficient mice. J Clin Invest. 2004; 114(5):634-42. PMC: 514589. DOI: 10.1172/JCI21851. View

Cunha R, Sebastiao A . Extracellular metabolism of adenine nucleotides and adenosine in the innervated skeletal muscle of the frog. Eur J Pharmacol. 1991; 197(1):83-92. DOI: 10.1016/0014-2999(91)90368-z. View

Martucci C, Trovato A, Costa B, Borsani E, Franchi S, Magnaghi V . The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1 beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice. Pain. 2007; 137(1):81-95. DOI: 10.1016/j.pain.2007.08.017. View

Zylka M, Sowa N, Taylor-Blake B, Twomey M, Herrala A, Voikar V . Prostatic acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine. Neuron. 2008; 60(1):111-22. PMC: 2629077. DOI: 10.1016/j.neuron.2008.08.024. View

Sawynok J, Reid A, Poon A . Peripheral antinociceptive effect of an adenosine kinase inhibitor, with augmentation by an adenosine deaminase inhibitor, in the rat formalin test. Pain. 1998; 74(1):75-81. DOI: 10.1016/S0304-3959(97)00153-X. View

Kelly R . Acupuncture for pain. Am Fam Physician. 2009; 80(5):481-4. View

Zijlstra F, van den Berg-de Lange I, Huygen F, Klein J . Anti-inflammatory actions of acupuncture. Mediators Inflamm. 2003; 12(2):59-69. PMC: 1781596. DOI: 10.1080/0962935031000114943. View

Fredholm B . Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ. 2007; 14(7):1315-23. DOI: 10.1038/sj.cdd.4402132. View

Lohse M, Klotz K, Schwabe U, Cristalli G, Vittori S, Grifantini M . 2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1988; 337(6):687-9. DOI: 10.1007/BF00175797. View

10.

Sun D, Samuelson L, Yang T, Huang Y, Paliege A, Saunders T . Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors. Proc Natl Acad Sci U S A. 2001; 98(17):9983-8. PMC: 55564. DOI: 10.1073/pnas.171317998. View

11.

Salter M, Henry J . Evidence that adenosine mediates the depression of spinal dorsal horn neurons induced by peripheral vibration in the cat. Neuroscience. 1987; 22(2):631-50. DOI: 10.1016/0306-4522(87)90359-9. View

12.

Reeve A, Dickenson A . Electrophysiological study on spinal antinociceptive interactions between adenosine and morphine in the dorsal horn of the rat. Neurosci Lett. 1995; 194(1-2):81-4. DOI: 10.1016/0304-3940(95)11732-c. View

13.

Eisenach J, Hood D, Curry R, Sawynok J, Yaksh T, Li X . Intrathecal but not intravenous opioids release adenosine from the spinal cord. J Pain. 2004; 5(1):64-8. DOI: 10.1016/j.jpain.2003.10.001. View

14.

Sichardt K, Nieber K . Adenosine A(1) receptor: Functional receptor-receptor interactions in the brain. Purinergic Signal. 2008; 3(4):285-98. PMC: 2072922. DOI: 10.1007/s11302-007-9065-z. View

15.

Li W, Cui K, Li N, Gu Q, Schwarz W, Ding G . Analgesic effect of electroacupuncture on complete Freund's adjuvant-induced inflammatory pain in mice: a model of antipain treatment by acupuncture in mice. Jpn J Physiol. 2005; 55(6):339-44. DOI: 10.2170/jjphysiol.RP001505. View

16.

Takakura N, Yajima H . Analgesic effect of acupuncture needle penetration: a double-blind crossover study. Open Med. 2009; 3(2):e54-61. PMC: 2765771. View

17.

. NIH Consensus Conference. Acupuncture. JAMA. 1998; 280(17):1518-24. View

18.

Culliton B . Acupuncture: Fertile Ground for Faddists and Serious NIH Research. Science. 1972; 177(4049):592-4. DOI: 10.1126/science.177.4049.592. View

19.

Volonte M, Yuln G, Quiroga P, Consolini A . Development of an HPLC method for determination of metabolic compounds in myocardial tissue. J Pharm Biomed Anal. 2004; 35(3):647-53. DOI: 10.1016/j.jpba.2004.02.002. View

20.

Li J, King N, Sinoway L . ATP concentrations and muscle tension increase linearly with muscle contraction. J Appl Physiol (1985). 2003; 95(2):577-83. DOI: 10.1152/japplphysiol.00185.2003. View