PAIN
Volume 150, Issue 3 , Pages 401-413 , September 2010

Inhibition of microglial P2X4 receptors attenuates morphine tolerance, Iba1, GFAP and μ opioid receptor protein expression while enhancing perivascular microglial ED2

  • Ryan J. Horvath

      Affiliations

    • Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    • Neuroscience Center at Dartmouth, Lebanon, NH 03756, USA
    • ,
  • E. Alfonso Romero-Sandoval

      Affiliations

    • Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    • Neuroscience Center at Dartmouth, Lebanon, NH 03756, USA
    • Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA
    • ,
  • Joyce A. De Leo

      Affiliations

    • Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    • Neuroscience Center at Dartmouth, Lebanon, NH 03756, USA
    • Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA
    • Corresponding Author InformationCorresponding author. Address: Dartmouth Medical School, HB 7650, Hanover, NH 03755, USA. Tel.: + 1 603 650 1667; fax: +1 603 650 8525.

Received 12 October 2009 ,Revised 24 February 2010 ,Accepted 26 February 2010.

References 

  1. Ammon-Treiber S, Hollt V. Morphine-induced changes of gene expression in the brain. Addict Biol. 2005;10:81–89
  2. Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci. 1984;7:309–338
  3. Bauer J, Huitinga I, Zhao W, Lassmann H, Hickey WF, Dijkstra CD. The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis. Glia. 1995;15:437–446
  4. Calvo CF, Cesselin F, Gelman M, Glowinski J. Identification of an opioid peptide secreted by rat embryonic mixed brain cells as a promoter of macrophage migration. Eur J Neurosci. 2000;12:2676–2684
  5. Chen SR, Pan HL. Blocking mu opioid receptors in the spinal cord prevents the analgesic action by subsequent systemic opioids. Brain Res. 2006;1081:119–125
  6. Chen YP, Chen SR, Pan HL. Systemic morphine inhibits dorsal horn projection neurons through spinal cholinergic system independent of descending pathways. J Pharmacol Exp Ther. 2005;314:611–617
  7. Colburn RW, DeLeo JA, Rickman AJ, Yeager MP, Kwon P, Hickey WF. Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat. J Neuroimmunol. 1997;79:163–175
  8. Cui Y, Liao XX, Liu W, Guo RX, Wu ZZ, Zhao CM, et al. A novel role of minocycline: attenuating morphine antinociceptive tolerance by inhibition of p38 MAPK in the activated spinal microglia. Brain Behav Immun. 2008;22(1):114–123
  9. DeLeo JA, Colburn RW, Rickman AJ, Yeager MP. Intrathecal catheterization alone induces neuroimmune activation in the rat. Eur J Pain. 1997;1:115–122
  10. Droste A, Sorg C, Hogger P. Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family. Biochem Biophys Res Commun. 1999;256:110–113
  11. Gao YJ, Zhang L, Samad OA, Suter MR, Yasuhiko K, Xu ZZ, et al. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain. J Neurosci. 2009;29(13):4096–4108
  12. Gong QJ, Li YY, Xin WJ, Zang Y, Ren WJ, Wei XH, et al. ATP induces long-term potentiation of C-fiber-evoked field potentials in spinal dorsal horn: the roles of P2X4 receptors and p38 MAPK in microglia. Glia. 2009;57(6):583–591
  13. Graeber MB, Streit WJ, Kreutzberg GW. Identity of ED2-positive perivascular cells in rat brain. J Neurosci Res. 1989;22:103–106
  14. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10:1387–1394
  15. Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32:77–88
  16. Hickey WF, Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988;239:290–292
  17. Honda S, Sasaki Y, Ohsawa K, Imai Y, Nakamura Y, Inoue K, et al. Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J Neurosci. 2001;21(6):1975–1982
  18. Horvath RJ, DeLeo JA. Morphine enhances microglial migration through modulation of P2X4 receptor signaling. J Neurosci. 2009;29:998–1005
  19. Inoue K. The function of microglia through purinergic receptors: neuropathic pain and cytokine release. Pharmacol Ther. 2006;109:210–226
  20. Irino Y, Nakamura Y, Inoue K, Kohsaka S, Ohsawa K. Akt activation is involved in P2Y12 receptor-mediated chemotaxis of microglia. J Neurosci Res. 2008;86:1511–1519
  21. Lacroix-Fralish ML, Tawfik VL, Tanga FY, Spratt KF, DeLeo JA. Differential spinal cord gene expression in rodent models of radicular and neuropathic pain. Anesthesiology. 2006;104:1283–1292
  22. Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, et al. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain. 2005;115(1–2):71–83
  23. Maderspach K, Solomonia R. Glial and neuronal opioid receptors: apparent positive cooperativity observed in intact cultured cells. Brain Res. 1988;441:41–47
  24. Mayer DJ, Mao J, Holt J, Price DD. Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions. Proc Natl Acad Sci USA. 1999;96:7731–7736
  25. Mika J. Modulation of microglia can attenuate neuropathic pain symptoms and enhance morphine effectiveness. Pharmacol Rep. 2008;60:297–307
  26. Ohsawa K, Irino Y, Nakamura Y, Akazawa C, Inoue K, Kohsaka S. Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis. Glia. 2007;55:604–616
  27. Pankratov Y, Lalo U, Verkhratsky A, North RA. Vesicular release of ATP at central synapses. Pflugers Arch. 2006;452:589–597
  28. Porreca F, Burgess SE, Gardell LR, Vanderah TW, Malan TP, Ossipov MH, et al. Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the mu-opioid receptor. J Neurosci. 2001;21(14):5281–5288
  29. Raehal KM, Bohn LM. Mu opioid receptor regulation and opiate responsiveness. AAPS J. 2005;7:E587–591
  30. Raghavendra V, Rutkowski MD, DeLeo JA. The role of spinal neuroimmune activation in morphine tolerance/hyperalgesia in neuropathic and sham-operated rats. J Neurosci. 2002;22:9980–9989
  31. Raghavendra V, Tanga F, DeLeo JA. Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther. 2003;306:624–630
  32. Raghavendra V, Tanga F, Rutkowski MD, DeLeo JA. Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines. Pain. 2003;104:655–664
  33. Raghavendra V, Tanga FY, DeLeo JA. Attenuation of morphine tolerance, withdrawal-induced hyperalgesia, and associated spinal inflammatory immune responses by propentofylline in rats. Neuropsychopharmacology. 2004;29:327–334
  34. Romero-Sandoval A, Chai N, Nutile-McMenemy N, DeLeo JA. A Comparison of Spinal Iba1 and GFAP expression in Rodent Models of Acute and Chronic Pain. Brain Res 2008.
  35. Romero-Sandoval A, Eisenach JC. Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision. Anesthesiology. 2007;106:787–794
  36. Romero-Sandoval A, Nutile-McMenemy N, DeLeo JA. Spinal microglial and perivascular cell cannabinoid receptor type 2 activation reduces behavioral hypersensitivity without tolerance after peripheral nerve injury. Anesthesiology. 2008;108:722–734
  37. Romero-Sandoval EA, Horvath RJ, DeLeo JA. Neuroimmune interactions and pain: focus on glial-modulating targets. Curr Opin Investig Drugs. 2008;9:726–734
  38. Sawynok J, Downie JW, Reid AR, Cahill CM, White TD. ATP release from dorsal spinal cord synaptosomes: characterization and neuronal origin. Brain Res. 1993;610:32–38
  39. Sawynok J, Sweeney MI, White TD. Adenosine release may mediate spinal analgesia by morphine. Trends Pharmacol Sci. 1989;10:186–189
  40. Sweeney MI, White TD, Sawynok J. Morphine, capsaicin and K+ release purines from capsaicin-sensitive primary afferent nerve terminals in the spinal cord. J Pharmacol Exp Ther. 1989;248:447–454
  41. Sweitzer SM, Hickey WF, Rutkowski MD, Pahl JL, DeLeo JA. Focal peripheral nerve injury induces leukocyte trafficking into the central nervous system: potential relationship to neuropathic pain. Pain. 2002;100:163–170
  42. Tawfik VL, LaCroix-Fralish ML, Nutile-McMenemy N, DeLeo JA. Transcriptional and translational regulation of glial activation by morphine in a rodent model of neuropathic pain. J Pharmacol Exp Ther. 2005;313:1239–1247
  43. Tawfik VL, Nutile-McMenemy N, Lacroix-Fralish ML, Deleo JA. Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury. Brain Behav Immun. 2007;21:238–246
  44. Tsuda M, Kuboyama K, Inoue T, Nagata K, Tozaki-Saitoh H, Inoue K. Behavioral phenotypes of mice lacking purinergic P2X4 receptors in acute and chronic pain assays. Mol Pain. 2009;5:28
  45. Tsuda M, Shigemoto-Mogami Y, Koizumi S, Mizokoshi A, Kohsaka S, Salter MW, et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature. 2003;424(6950):778–783
  46. Turchan-Cholewo J, Dimayuga FO, Ding Q, Keller JN, Hauser KF, Knapp PE, et al. Cell-specific actions of HIV-Tat and morphine on opioid receptor expression in glia. J Neurosci Res. 2008;86(9):2100–2110
  47. Ulmann L, Hatcher JP, Hughes JP, Chaumont S, Green PJ, Conquet F, et al. Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain. J Neurosci. 2008;28(44):11263–11268
  48. Wang Z, Ma W, Chabot JG, Quirion R. Cell-type specific activation of p38 and ERK mediates calcitonin gene-related peptide involvement in tolerance to morphine-induced analgesia. FASEB J. 2009;23:2576–2586
  49. Williams JT, Christie MJ, Manzoni O. Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev. 2001;81:299–343
  50. Williams KC, Corey S, Westmoreland SV, Pauley D, Knight H, deBakker C, et al. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J Exp Med. 2001;193:905–915
  51. Yu LC, Hou JF, Fu FH, Zhang YX. Roles of calcitonin gene-related peptide and its receptors in pain-related behavioral responses in the central nervous system. Neurosci Biobehav Rev. 2009;33:1185–1191
  52. Zhang X, Chen Y, Wang C, Huang LY. Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia. Proc Natl Acad Sci USA. 2007;104:9864–9869
  53. Zhang Z, Chen G, Zhou W, Song A, Xu T, Luo Q, et al. Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol. 2007;9(8):945–953
  54. Zhang Z, Zhang ZY, Fauser U, Schluesener HJ. Mechanical allodynia and spinal up-regulation of P2X(4) receptor in experimental autoimmune neuritis rats. Neuroscience. 2008;152:495–501
  55. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16:109–110
  56. Zwadlo G, Voegeli R, Osthoff KS, Sorg C. A monoclonal antibody to a novel differentiation antigen on human macrophages associated with the down-regulatory phase of the inflammatory process. Exp Cell Biol. 1987;55:295–304

PII: S0304-3959(10)00146-6

doi: 10.1016/j.pain.2010.02.042

PAIN
Volume 150, Issue 3 , Pages 401-413 , September 2010

Article Tools

* Image Usage & Resolution