Adenosine pp 343-360 | Cite as

Adenosine and Pain

Chapter

Abstract

Adenosine A1 receptors (A1Rs) have been shown to be involved in antinociception in preclinical models for several decades. Thus, systemic, peripheral, spinal, and supraspinal administration of A1R agonists universally produces antinociception in nociceptive, inflammatory, and neuropathic pain models. The clinical potential for adenosine (given intravenously), or A1R ligands (given systemically or spinally) to produce analgesia in humans was supported by earlier trials, but more recent, larger controlled trials have generally not demonstrated analgesic activity for postoperative pain. Adenosine A2ARs have more complex effects on pain, generating pronociceptive effects peripherally and spinally, but antinociceptive effects supraspinally. The presence of A2ARs on astrocytes and microglia within the spinal cord may be particularly important for their pronociceptive actions in states of nerve injury. There is also a report that ultralow doses of A2AR agonists produce long lasting antinociception in such states. Manipulation of endogenous levels of adenosine by inhibiting adenosine kinase represented a promising novel approach, but development in this area is no longer active. Recent data have demonstrated that specific ectonucleotidases are localized on sensory afferent neurons, and that spinal delivery of recombinant forms of these enzymes produce long-lasting antinociceptive actions; this led to the suggestion that manipulating ectonucleotidases may represent a potential new approach for development. Additional observations have implicated tissue release of nucleotides and adenosine in acupuncture analgesia, and shown analgesia results from peripheral actions at adenosine A1Rs. Finally, other recent observations indicate that caffeine, which inhibits both A1- and A2ARs with high affinity, blocks antinociception in preclinical studies by several drugs currently used to treat pain in humans. As caffeine is widely consumed, it will be important to attend to caffeine intake in future trial design with respect to evaluating novel therapies that use these receptor systems, some existing analgesics, as well as acupuncture analgesia.

Keywords

Adenosine Antinociception Analgesia Adenosine kinase inhibitors Ectonucleotidases Acupuncture Caffeine Spinal cord 

References

  1. Abo-Salem OM, Hayallah AM, Bilkei-Gorzo A, Filipek B, Zimmer A, Müller CE (2004) Antinociceptive effects of novel A2B adenosine receptor antagonists. J Pharmacol Exp Ther 308:358–366CrossRefPubMedGoogle Scholar
  2. Ackley MA, Governo RJM, Cass CE, Young JD, Baldwin SA, King AE (2003) Control of glutamatergic neurotransmission in the rat spinal dorsal horn by nucleoside transporter ENT1. J Physiol 548:507–517CrossRefPubMedGoogle Scholar
  3. Bagley EE, Vaughan CW, Christie MJ (1999) Inhibition by adenosine receptor agonists of synaptic transmission in rat periaqueductal grey neurons. J Physiol 516:219–225CrossRefPubMedGoogle Scholar
  4. Bailey A, Matthes H, Kieffer B, Slowe S, Hourani SMO, Kitchen I (2002) Quantitative autoradiography of adenosine receptors and NBTI-sensitive adenosine transporters in the brains and spinal cords of mice deficient in the μ-opioid receptor gene. Brain Res 943:68–79CrossRefPubMedGoogle Scholar
  5. Bantel C, Li X, Eisehach JC (2003) Intraspinal adenosine induces spinal cord norepinephrine release in spinal nerve-ligated rats but not in normal or sham controls. Anesthesiology 98:1461–1466CrossRefPubMedGoogle Scholar
  6. Bastia E, Varani K, Monopoli A, Bertorelli R (2002) Effects of A1 and A2A adenosine receptor ligands in mouse acute models of pain. Neurosci Lett 328:241–244CrossRefPubMedGoogle Scholar
  7. Benito-Garcia E, Heller JE, Chibnik LB, Maher NE, Matthews HM, Bilics JA, Weinblatt ME, Shadick NA (2006) Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid arthritis. J Rheumatol 33:1275–1281PubMedGoogle Scholar
  8. Bilkei-Gorzo A, Abo-Salem OM, Hayallah AM, Michel K, Müller CE, Zimmer A (2008) Adenosine receptor subtype-selective antagonists in inflammation and hyperalgesia. Naunyn-Schmiedeberg’s Arch Pharmacol 377:65–76CrossRefGoogle Scholar
  9. Boison D, Chen JF, Fredholm BB (2010) Adenosine signalling and function in glial cells. Cell Death Differ 17:1071–1082CrossRefPubMedGoogle Scholar
  10. Borghi V, Przewlocka B, Labuz D, Maj M, Ilona O, Pavone F (2002) Formalin-induced pain and μ-opioid receptor density in brain and spinal cord are modulated by A1 and A2A adenosine agonists in mice. Brain Res 956:339–348CrossRefPubMedGoogle Scholar
  11. Brooke RE, Deuchars J, Deuchars SA (2004) Input-specific modulation of neurotransmitter release in the lateral horn of the spinal cord via adenosine receptors. J Neurosci 24:127–137CrossRefPubMedGoogle Scholar
  12. Bura SA, Nadal X, Ledent C, Maldonado R, Valverde O (2008) A2A adenosine receptor regulates glia proliferation and pain after peripheral nerve injury. Pain 140:95–103CrossRefPubMedGoogle Scholar
  13. By Y, Condo J, Durand-Gorde JM, Lejeune PJ, Mallet B, Guieu R, Ruf G (2011) Intracerebroventricular injection of an agonist-like monoclonal antibody to adenosine A2A receptor has antinociceptive effects in mice. J Neuroimmunol 230:178–182CrossRefPubMedGoogle Scholar
  14. Carruthers AM, Sellers LA, Jenkins DW, Jarvie EM, Feniuk W, Humphrey PPA (2001) Adenosine A1 receptor-mediated inhibition of protein kinase A-induced calcitonin gene-related peptide release from rat trigeminal neurons. Mol Pharmacol 59:1533–1541PubMedGoogle Scholar
  15. Choca JI, Green RD, Proudfit HK (1988) Adenosine A1 and A2 receptors of the substantia gelatinosa are located predominantly on intrinsic neurons: an autoradiography study. J Pharmacol Exp Ther 247:757–764PubMedGoogle Scholar
  16. Crain SM, Shen K-F (2000) Antagonists of excitatory opioid receptor functions enhance morphine’s analgesic potency and attenuate opioid tolerance/dependence liability. Pain 84:121–131CrossRefPubMedGoogle Scholar
  17. Curros-Criado MM, Herrero JF (2005) The antinociceptive effects of the systemic adenosine A1 receptor agonist CPA in the absence and in the presence of spinal cord sensitization. Pharmacol Biochem Behav 82:721–726CrossRefPubMedGoogle Scholar
  18. DeLeo JA, Colburn RW, Rickman AJ, Yeager MP (1997) Intrathecal catheterization alone induces neuroimmune activation in the rat. Eur J Pain 1:115–122CrossRefPubMedGoogle Scholar
  19. DeLeo JA, Tawfik VL, LaCroix-Fralish ML (2006) The tetrapartite synapse: path to CNS sensitization and chronic pain. Pain 122:17–21CrossRefGoogle Scholar
  20. Deuchars SA, Brooke RE, Deuchars J (2001) Adenosine A1 receptors reduce release from excitatory but not inhibitory synaptic inputs onto lateral horn neurons. J Neurosci 21:6308–6320PubMedGoogle Scholar
  21. Dickenson A, Suzuki R, Reeve AJ (2000) Adenosine as a potential analgesic target in inflammatory and neuropathic pains. CNS Drugs 13:77–85CrossRefGoogle Scholar
  22. Doak GJ, Sawynok J (1995) Complex role of peripheral adenosine in the genesis of the response to subcutaneous formalin in the rat. Eur J Pharmacol 281:311–318CrossRefPubMedGoogle Scholar
  23. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55CrossRefPubMedGoogle Scholar
  24. Erion MD, Wiesner JB, Rosengren S, Ugarkar B, Boyer SH, Tsuchiya M, Nakane M, Pettersen BA, Nagahisa A (2000) Therapeutic potential of adenosine kinase inhibitors as analgesic agents. Drug Dev Res 50:22, S14-06Google Scholar
  25. Esser MJ, Sawynok J (2000) Caffeine blockade of the thermal antihyperalgesic effect of acute amitriptyline in a rat model of neuropathic pain. Eur J Pharmacol 399:131–139CrossRefPubMedGoogle Scholar
  26. Ferré S, Diamond I, Goldberg SR, Yao L, Hourani SMO, Huang ZL, Urade Y, Kitchen I (2007) Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry. Implications for drug addiction, sleep and pain. Prog Neurobiol 83:332–347CrossRefPubMedGoogle Scholar
  27. Fields RD, Ni Y (2010) Nonsynaptic communication through ATP release from volume-activated anion channels in axons. Sci Signal 3(142):ra73CrossRefPubMedGoogle Scholar
  28. Frary CD, Johnson RK, Wang MQ (2005) Food sources and intake of caffeine in the diets of persons in the United States. J Am Diet Assoc 105:110–113CrossRefPubMedGoogle Scholar
  29. Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvaratau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133PubMedGoogle Scholar
  30. Fredholm BB, Ijzerman AP, Jacobson KA, Klotz KN, Linden J (2001a) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53:527–552PubMedGoogle Scholar
  31. Fredholm BB, Irenius E, Kull B, Schulte G (2001b) Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells. Biochem Pharmacol 61:443–448CrossRefPubMedGoogle Scholar
  32. Fukuda KI, Hayashida M, Fukunaga A, Kasahara M, Koukita Y, Ichinohe T, Kaneko Y (2007) Pain-relieving effects of intravenous ATP in chronic intractable orofacial pain: an open-label study. J Anesth 21:24–30CrossRefPubMedGoogle Scholar
  33. Gan TJ, Habib AS (2007) Adenosine as a non-opioid analgesic in the perioperative setting. Anesth Analg 105:487–494CrossRefPubMedGoogle Scholar
  34. Gessi S, Merighi S, Vareni K, Leung E, MacLennan S, Borea PA (2008) The A3 adenosine receptor: an enigmatic player in cell biology. Pharmacol Ther 117:123–140CrossRefPubMedGoogle Scholar
  35. Godfrey L, Yan L, Clarke GD, Ledent C, Kitchen I, Hourani SMO (2006) Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice. Eur J Pharmacol 531:80–86CrossRefPubMedGoogle Scholar
  36. Goldman N, Chen M, Fujita T, Wu Q, Peng W, Liu W, Jensen TK, Pai Y, Wang F, Han X, Chen JF, Schnermann J, Takano T, Bekar L, Tieu K, Nedergaard M (2010) Adenosine A1 receptors mediate local antinociceptive effects of acupuncture. Nat Neurosci 13:883–889CrossRefPubMedGoogle Scholar
  37. Golembiowska K, White TD, Sawynok J (1996) Adenosine kinase inhibitors augment release of adenosine from spinal cord slices. Eur J Pharmacol 307:157–162CrossRefPubMedGoogle Scholar
  38. Gong Q-J, Li Y-Y, Xin W-J, Wei X-H, Wang J, Liu Y, Liu C-C, Li Y-Y, Liu X-G (2010) Differential effects of adenosine A1 receptor on pain-related behavior in normal and nerve-injured rats. Brain Res 1361:23–30CrossRefPubMedGoogle Scholar
  39. Granados-Soto V, Castaneda-Hernández G (1999) A review of the pharmacokinetic and pharmacodynamic factors in the potentiation of the antinociceptive effect of nonsteroidal anti-inflammatory drugs by caffeine. J Pharmacol Toxicol 42:67–72CrossRefGoogle Scholar
  40. Haas HL, Selbach O (2000) Functions of neuronal adenosine receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 362:375–381CrossRefGoogle Scholar
  41. Habib AS, Minkowitz H, Osborn T, Ogunnaike B, Candiotti K, Viscusi E, Gu J, Creed MR, Gan TJ (2008) Phase 2, double-blind, placebo-controlled, dose-response trial of intravenous adenosine for perioperative analgesia. Anesthesiology 109:1085–1091CrossRefPubMedGoogle Scholar
  42. Handa T, Fukuda KI, Hayashida M, Koukita Y, Ichinohe T, Kaneko Y (2009) Effects of intravenous adenosine 5’-triphosphate on intraoperative hemodynamics and postoperative pain in patients undergoing major orofacial surgery: a double-blind placebo-controlled study. J Anesth 23:315–322CrossRefPubMedGoogle Scholar
  43. Haskó G, Csóka B, Németh ZH, Vizi ES, Pacher P (2009) A2B adenosine receptors in immunity and inflammation. Trends Immunol 30:263–270CrossRefPubMedGoogle Scholar
  44. Hayashida M, Fukuda KI, Fukunaga A (2005) Clinical application of adenosine and ATP for pain control. J Anesth 19:225–235CrossRefPubMedGoogle Scholar
  45. Hussey MJ, Clarke GD, Ledent C, Hourani SMO, Kitchen I (2007) Reduced response to the formalin test and lowered spinal NMDA glutamate receptor binding in adenosine A2A receptor knockout mice. Pain 129:287–294CrossRefPubMedGoogle Scholar
  46. Johansson B, Halldner L, Dunwiddie TV, Masino SA, Poelchen W, Giménez-Llort L, Escorihuela RM, Fernández-Teruel A, Wiesenfeld-Hallin Z, Xu X-J, Hårdemark A, Betsholtz C, Herlenius E, Fredholm BB (2001) Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor. Proc Natl Acad Sci 98:9407–9412CrossRefPubMedGoogle Scholar
  47. Kaelin-Lang A, Lauterburg T, Burgunder JM (1998) Expression of adenosine A2A receptor gene in rat dorsal root and autonomic ganglia. Neurosci Lett 246:21–24CrossRefPubMedGoogle Scholar
  48. Karlsten R, Gordh T, Post C (1992) Local antinociceptive and hyperalgesic effects in the formalin test after peripheral administration of adenosine analogues in mice. Pharmacol Toxicol 70:434–438CrossRefPubMedGoogle Scholar
  49. Keil GJ, DeLander GE (1994) Adenosine kinase and adenosine deaminase inhibition modulate spinal adenosine- and opioid agonist-induced antinociception in mice. Eur J Pharmacol 271:37–46CrossRefPubMedGoogle Scholar
  50. Khasar SG, Wang JF, Taiwo YO, Heller PH, Green PG, Levine JD (1995) Mu-opioid agonist enhancement of prostaglandin-induced hyperalgesia in the rat: a G-protein βγ subunit-mediated effect? Neuroscience 67:189–195CrossRefPubMedGoogle Scholar
  51. King T, Vera-Portocarrero L, Gutierrez T, Vanderah TW, Dussor G, Lai J, Fields HL, Porreca F (2009) Unmasking the tonic-aversive state in neuropathic pain. Nat Neurosci 12:1364–1366CrossRefPubMedGoogle Scholar
  52. Kolesnikov YA, Jain S, Wilson R, Pasternak G (1996) Peripheral morphine analgesia: synergy with central sites and a target of morphine tolerance. J Pharmacol Exp Ther 279:502–506PubMedGoogle Scholar
  53. Langevin HM, Bouffard NA, Badger GJ, Churchill DL, Howe AK (2006) Subcutaneous tissue fibroblast cytoskeletal remodeling induced by acupuncture: evidence for a mechanotransduction-based mechanism. J Cell Physiol 207:767–774CrossRefPubMedGoogle Scholar
  54. Lao L-J, Kawasaki Y, Yang K, Fujita T, Kumamoto E (2004) Modulation by adenosine of Aδ and C primary-afferent glutamatergic transmission in adult rat substantia gelatinosa neurons. Neuroscience 125:221–231CrossRefPubMedGoogle Scholar
  55. Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G, Parmentier M (1997) Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2A receptor. Nature 388:674–678CrossRefPubMedGoogle Scholar
  56. Lee Y-W, Yaksh TL (1996) Pharmacology of the spinal adenosine receptor which mediates the antiallodynic action of intrathecal adenosine agonists. J Pharmacol Exp Ther 277:1642–1648PubMedGoogle Scholar
  57. Li X, Eisenach JC (2005) Adenosine reduces glutamate release in rat spinal synaptosomes. Anesthesiology 103:1060–1065CrossRefPubMedGoogle Scholar
  58. Li J, Perl ER (1994) Adenosine inhibition of synaptic transmission in the substantia gelatinosa. J Neurophysiol 72:1611–1621PubMedGoogle Scholar
  59. Li L, Hao JX, Fredholm BB, Schulte G, Wiesenfeld-Hallin Z, Xu XJ (2010) Peripheral adenosine A2A receptors are involved in carrageenan-induced mechanical hyperalgesia in mice. Neuroscience 170:923–928CrossRefPubMedGoogle Scholar
  60. Lima FO, Souza GR, Verri WA, Parada CA, Ferreira SH, Cunha FQ, Cunha TM (2010) Direct blockade of inflammatory hypernociception by peripheral A1 adenosine receptors: involvement of the NO/cGMP/PKG/KATP signaling pathway. Pain 151:506–515CrossRefPubMedGoogle Scholar
  61. Liu XJ, White TD, Sawynok J (2002) Enhanced release of adenosine in rat hindpaw following spinal nerve ligation: involvement of capsaicin-sensitive sensory afferents. Neuroscience 114:379–387CrossRefPubMedGoogle Scholar
  62. Loram LC, Harrison JA, Sloane EM, Hutchison MR, Sholar P, Taylor FR, Berkelhammer D, Coats BD, Poole S, Milligan ED, Maier SF, Riegers J, Watkins LR (2009) Enduring reversal of neuropathic pain by a single intrathecal injection of adenosine 2A receptor agonists: a novel therapy for neuropathic pain. J Neurosci 29:14015–14025CrossRefPubMedGoogle Scholar
  63. Maione S, de Novellis V, Cappellacci L, Palazzo E, Vita D, Luongo L, Stella L, Franchetti P, Marabese I, Rossi F, Grifantini M (2007) The antinociceptive effect of 2-chloro-2’-C-methyl-N6-cyclopentyladenosine (2’-Me-CCPA), a highly selective adenosine A1 receptor agonist, in the rat. Pain 131:281–292CrossRefPubMedGoogle Scholar
  64. Marchand S, Li J, Charest J (1995) Effects of caffeine on analgesia from transcutaneous electrical nerve stimulation. N Eng J Med 333:325–326CrossRefGoogle Scholar
  65. Matsuka Y, Ono T, Iwase H, Mitrirattanakul S, Omote KS, Cho T, Lam YYN, Synder B, Spigelman I (2008) Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats. Mol Pain 4:66CrossRefPubMedGoogle Scholar
  66. Mauborgne A, Poliénor H, Hamon M, Cesselin F, Bourgoin S (2002) Adenosine receptor-mediated control of in vitro release of pain-related neuropeptides from the rat spinal cord. Eur J Pharmacol 441:47–55CrossRefPubMedGoogle Scholar
  67. McGaraughty S, Chu K, Wismer CT, Mikusa J, Zhu CZ, Cowart M, Kowaluk EA, Jarvis MF (2001) Effects of A-134974, a novel ADO kinase inhibitor, on carrageenan-induced inflammatory hyperalgesia and locomotor activity in rats: evaluation of the sites of action. J Pharmacol Exp Ther 296:501–509PubMedGoogle Scholar
  68. McGaraughty S, Cowart M, Jarvis MF, Berman RF (2005) Anticonvulsant and antinociceptive actions of novel adenosine kinase inhibitors. Curr Top Med Chem 5:43–58CrossRefPubMedGoogle Scholar
  69. Nascimento FP, Figueredo SM, Marcon R, Martins DF, Macedo SJ, Lima DAN, Almeida RC, Ostroski RM, Rodrigues ALS, Santos ARS (2010) Inosine reduces pain-related behavior in mice: involvement of adenosine A1 and A2A receptor subtypes and protein kinase C pathways. J Pharmacol Exp Ther 334:590–598CrossRefPubMedGoogle Scholar
  70. Nelapa I, Vetulani J, Borghi V, Kowalska M, Przewlocka B, Roman AD, Pavone F (2010) Changes induced by formalin pain in central α1-receptor density are modulated by adenosine receptor agonists. J Neural Transm 117:549–558CrossRefGoogle Scholar
  71. Nesher G, Mates M, Zevin S (2003) Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis. Arthritis Rheum 48:571–572CrossRefPubMedGoogle Scholar
  72. NIH Consensus Conference (1998) Acupuncture. J Am Med Assoc 280:1518–1524CrossRefGoogle Scholar
  73. Ocaña M, Bayens JM (1994) Role of ATP-sensitive K+-channels in antinociception induced by R-PIA, an adenosine A1 receptor agonist. Naunyn Schmiedeberg’s Arch Pharmacol 350:57–62CrossRefGoogle Scholar
  74. Palmer H, Graham G, Williams K, Day R (2010) A risk-benefit assessment of paracetamol (acetaminophen) combined with caffeine. Pain Med 11:951–965CrossRefPubMedGoogle Scholar
  75. Patel MK, Pinnock RD, Lee K (2001) Adenosine exerts multiple effects in dorsal horn neurones of the adult rat spinal cord. Brain Res 920:19–26CrossRefPubMedGoogle Scholar
  76. Poon A, Sawynok J (1998) Antinociception by adenosine analogs and inhibitors of adenosine metabolism in an inflammatory thermal hyperalgesia model in the rat. Pain 74:235–245CrossRefPubMedGoogle Scholar
  77. Raffa RB, Stone DJJR, Tallarida RJ (2000) Discovery of “self-synergistic” spinal/supraspinal antinociception produced by acetaminophen (paracetamol). J Pharmacol Exp Ther 295:291–294PubMedGoogle Scholar
  78. Ramos-Zepeda G, Schröder W, Rosenow S, Herrero JF (2004) Spinal vs. supraspinal antinociceptive activity of the adenosine A1 receptor agonist cyclopentyl-adenosine in rats with inflammation. Eur J Pharmacol 499:247–256CrossRefPubMedGoogle Scholar
  79. Reeve AJ, Dickenson AH (1995) The roles of spinal adenosine receptors in the control of acute and more persistent nociceptive responses of dorsal horn neurons in the anaesthetized rat. Br J Pharmacol 116:2221–2228CrossRefPubMedGoogle Scholar
  80. Reeves JJ, Jones CA, Sheehan MJ, Cardey CJ, Whelan CJ (1997) Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and in vivo. Inflamm Res 46:180–184CrossRefPubMedGoogle Scholar
  81. Regaya I, Pham T, Andreotti N, Sauze N, Carrega L, Martin-Eauclaire MF, Jouirou B, Peragut JC, Vacher H, Rochat H, Devaux C, Sabatier JM, Guieu R (2004) Small conductance calcium-activated K+ channels, SkCa, but not voltage-gated K+ (Kv) channels, are implicated in the antinociception induced by CGS21680, a A2A adenosine receptor agonist. Life Sci 76:367–377CrossRefPubMedGoogle Scholar
  82. Renner B, Clarke G, Grattan T, Beisel A, Mueller C, Werner U, Kobal G, Brune K (2007) Caffeine accelerates absorption and enhances the analgesic effect of acetaminophen. J Clin Pharmacol 47:715–726CrossRefPubMedGoogle Scholar
  83. Reppert SM, Weaver DR, Stehle JH, Rivkees SA (1991) Molecular cloning and characterization of a rat A1-adenosine receptor that is widely expressed in brain and spinal cord. Mol Endocrinol 5:1037–1048CrossRefPubMedGoogle Scholar
  84. Riberio JA, Sebastiao AM, Mendoca A (2003) Adenosine receptors in the nervous system: pathophysiological implications. Prog Neurobiol 68:377–392CrossRefGoogle Scholar
  85. Rice ASC, Cimino-Brown D, Eisenach JC, Kontinen VK, Lacroix-Fralish ML, Machin I (2008) Animal models and the prediction of efficacy in clinical trials of analgesic drugs: a critical appraisal and call for uniform reporting standards. Pain 139:243–247CrossRefPubMedGoogle Scholar
  86. Santicioli P, Del Bianco E, Maggi CA (1993) Adenosine A1 receptors mediate the presynaptic inhibition of calcitonin gene-related peptide release by adenosine in the rat spinal cord. Eur J Pharmacol 231:139–142CrossRefPubMedGoogle Scholar
  87. Sawynok J (1998) Adenosine receptor activation and nociception. Eur J Pharmacol 347:1–11CrossRefPubMedGoogle Scholar
  88. Sawynok J, Liu XJ (2003) Adenosine in the spinal cord and periphery: release and regulation of pain. Prog Neurobiol 69:313–340CrossRefPubMedGoogle Scholar
  89. Sawynok J, Zarrindast MR, Reid AR, Doak GJ (1997) Adenosine A3 receptor activation produces nociceptive behavior and edema by release of histamine and 5-hydroxytryptamine. Eur J Pharmacol 333:1–7CrossRefPubMedGoogle Scholar
  90. Sawynok J, Reid AR, Fredholm BB (2008) Caffeine reverses antinociception by amitriptyline in wild type mice but not those lacking adenosine A1 receptors. Neurosci Lett 440:181–184CrossRefPubMedGoogle Scholar
  91. Sawynok J, Reid AR, Fredholm BB (2010) Caffeine reverses antinociception by oxcarbazepine by inhibition of adenosine A1 receptors: insights using knockout mice. Neurosci Lett 473:178–181CrossRefPubMedGoogle Scholar
  92. Schmidt AP, Böhmer AE, Antunes C, Schallenberger C, Porciúncula LO, Elisabetsky E, Lara DR, Souza DO (2009) Anti-nociceptive properties of the xanthine oxidase inhibitor allopurinal in mice: role of A1 adenosine receptors. Br J Pharmacol 156:163–172CrossRefPubMedGoogle Scholar
  93. Scholz J, Woolf CJ (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10:1361–1368CrossRefPubMedGoogle Scholar
  94. Schulte G, Robertson B, Fredholm BB, DeLander GE, Shortland P, Molander C (2003) Distribution of antinociceptive adenosine A1 receptors in the spinal cord dorsal horn, and relationship to primary afferents and neuronal subpopulations. Neuroscience 121:907–916CrossRefPubMedGoogle Scholar
  95. Sharma M, Mohta M, Chawla R (2006) Efficacy of intrathecal adenosine for postoperative pain relief. Eur J Anaesthesiol 23:449–453CrossRefPubMedGoogle Scholar
  96. Sneyd JR, Langton JA, Allan LG, Peacock JE, Rowbotham DJ (2007) Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction. Br J Anaesth 98:672–676CrossRefPubMedGoogle Scholar
  97. Sowa NA, Vadakkan KI, Zylka MJ (2009) Recombinant mouse PAP has pH-dependent ectonucleotidase activity and acts through A1-adenosine receptors to mediate antinociception. PLoS One 4:e4248CrossRefPubMedGoogle Scholar
  98. Sowa NA, Street SE, Vihko P, Zylka MJ (2010a) Prostatic acid phosphatase reduces thermal sensitivity and chronic pain sensitization by depleting phosphatidylinositol 4,5-bisphosphate. J Neurosci 30:10282–10293CrossRefPubMedGoogle Scholar
  99. Sowa NA, Taylor-Blake B, Zylka MJ (2010b) Ecto-5’-nucleotidase (CD73) inhibits nociception by hydrolyzing AMP to adenosine in nociceptive circuits. J Neurosci 30:2235–2244CrossRefPubMedGoogle Scholar
  100. Sowa NA, Voss M, Zylka MJ (2010c) Recombinant ecto-5’-nucleotidase (CD73) has long lasting antinociceptive effects that are dependent on adenosine A1 receptor activation. Mol Pain 6:20CrossRefPubMedGoogle Scholar
  101. Suzuki R, Gale A, Dickenson AH (2000) Altered effects of an A1 adenosine receptor agonist on the evoked responses of spinal dorsal horn neurons in a rat model of mononeuropathy. J Pain 1:99–110CrossRefGoogle Scholar
  102. Taiwo YO, Levine JD (1990) Direct cutaneous hyperalgesia induced by adenosine. Neuroscience 38:757–762CrossRefPubMedGoogle Scholar
  103. Tanase D, Baghdoyan HA, Lydic R (2002) Microinjection of an adenosine A1 agonist into the medial pontine reticular formation increases tail flick latency to thermal stimulation. Anesthesiology 97:1597–1601CrossRefPubMedGoogle Scholar
  104. Taylor-Blake B, Zylka MJ (2010) Prostatic acid phosphatase is expressed in peptidergic and nonpeptidergic nociceptive neurons of mice and rats. PLoS One 5:e8674CrossRefPubMedGoogle Scholar
  105. Tian L, Ji G, Wang C, Bai X, Lu Y, Xiong L (2010) Excitatory synaptic transmission in the spinal substantia gelatinosa is under an inhibitory tone of endogenous adenosine. Neurosci Lett 477:28–32CrossRefPubMedGoogle Scholar
  106. Tomić MA, Vučović SM, Stepanović-Petrović RM, Ugrešić N, Prostran MS, Bošković B (2004) The anti-hyperalgesic effects of carbamazepine and oxcarbazepine are attenuated by treatment with adenosine receptor antagonists. Pain 111:253–260CrossRefPubMedGoogle Scholar
  107. Wu W-P, Hao J-X, Halldner-Henricksson L, Xu XJ, Jacobson MA, Wiesenfeld-Hallin Z, Fredholm BB (2002) Decreased inflammatory pain due to reduced carrageenan-induced inflammation in mice lacking adenosine A3 receptors. Neuroscience 114:523–527CrossRefPubMedGoogle Scholar
  108. Wu W-P, Hao J-X, Halldner L, Lövdahl C, DeLander GE, Wisenfeldl-Hallin Z, Fredholm BB, Xu X-J (2005) Increased nociceptive response in mice lacking the adenosine A1 receptor. Pain 113:395–404CrossRefPubMedGoogle Scholar
  109. Yang D, Zhang Y, Nguyen HG, Koupenova M, Chauhan AK, Makitalo M, Jones MR, St. Hilaire C, Seldin DC, Toselli P, Lamperti E, Schreiber BM, Gavras H, Wagner DD, Ravid K (2006) The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest 116:1913–1923CrossRefPubMedGoogle Scholar
  110. Zahn PK, Straub H, Wenk M, Pogatzki-Zahn EM (2007) Adenosine A1 but not A2a receptor agonist reduces hyperalgesia caused by a surgical incision in rats. A pertussis toxin-sensitive G protein-dependent process. Anesthesiology 107:797–806CrossRefPubMedGoogle Scholar
  111. Zhao ZQ (2008) Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 85:355–375CrossRefPubMedGoogle Scholar
  112. Zhu CZ, Mikusa J, Chu K, Cowart M, Kowaluk EA, Jarvis MF (2001) A-134974, a novel ADO kinase inhibitor, relieves tactile allodynia via spinal sites of action in peripheral nerve injured rats. Brain Res 905:104–110CrossRefPubMedGoogle Scholar
  113. Zylka MJ (2010) Needling adenosine receptors for pain relief. Nat Neurosci 13:783–784CrossRefPubMedGoogle Scholar
  114. Zylka MJ (2011) Pain-relieving prospects for adenosine receptors and ectonucleotidases. Trends Mol Med 17:188–196CrossRefPubMedGoogle Scholar
  115. Zylka MJ, Sowa NA, Taylor-Blake B, Twomey MA, Herrala A, Voikar V, Vihko P (2008) Prostatic acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine. Neuron 60:111–122CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of PharmacologyDalhousie UniversityHalifaxCanada

Personalised recommendations