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PMID: 19837031 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Cellular and molecular mechanisms of pain.

Cell ·Vol. 139 ·No. 2 ·2009-10-16 ·Pages 267-84

Basbaum AI, Bautista DM, Scherrer G, Julius D

Abstract

The nervous system detects and interprets a wide range of thermal and mechanical stimuli, as well as environmental and endogenous chemical irritants. When intense, these stimuli generate acute pain, and in the setting of persistent injury, both peripheral and central nervous system components of the pain transmission pathway exhibit tremendous plasticity, enhancing pain signals and producing hypersensitivity. When plasticity facilitates protective reflexes, it can be beneficial, but when the changes persist, a chronic pain condition may result. Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.

MeSH Terms
Animals Chronic Disease Humans Neuronal Plasticity Nociceptors/physiology Pain/physiopathology
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Basbaum Allan I
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA. [email protected]
Bautista Diana M
Scherrer Grégory
Julius David
References (158)
158 references, click to expand
  1. Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli.
    Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9075-80 PMID: 19451647
  2. Thermal hyperalgesia as a marker of oxaliplatin neurotoxicity: a prospective quantified sensory assessment study.
    Pain. 2009 Aug;144(3):245-252 PMID: 19457614
  3. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes.
    Neuron. 2006 Dec 7;52(5):767-74 PMID: 17145499
  4. Localization of mechanosensitive channel TRPV4 in mouse skin.
    Neurosci Lett. 2003 Dec 26;353(3):189-92 PMID: 14665413
  5. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia.
    Neuron. 2002 Sep 26;36(1):57-68 PMID: 12367506
  6. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain.
    Nature. 2003 Aug 21;424(6951):938-42 PMID: 12931188
  7. TRPV2 is a component of osmotically sensitive cation channels in murine aortic myocytes.
    Circ Res. 2003 Oct 31;93(9):829-38 PMID: 14512441
  8. TRPA1 modulates mechanotransduction in cutaneous sensory neurons.
    J Neurosci. 2009 Apr 15;29(15):4808-19 PMID: 19369549
  9. Neuron-glia crosstalk gets serious: role in pain hypersensitivity.
    Curr Opin Anaesthesiol. 2008 Oct;21(5):570-9 PMID: 18784481
  10. A TRP channel that senses cold stimuli and menthol.
    Cell. 2002 Mar 8;108(5):705-15 PMID: 11893340
  11. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity.
    Nat Cell Biol. 2000 Oct;2(10):695-702 PMID: 11025659
  12. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.
    Cell. 2006 Mar 24;124(6):1269-82 PMID: 16564016
  13. Voltage-gated calcium channels and pain.
    Pain. 2006 Dec 15;126(1-3):5-9 PMID: 17084979
  14. Direct activation of the ion channel TRPA1 by Ca2+.
    Nat Neurosci. 2007 Mar;10(3):277-9 PMID: 17259981
  15. Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia.
    Circ Res. 2006 Sep 1;99(5):501-9 PMID: 16873722
  16. The receptors and coding logic for bitter taste.
    Nature. 2005 Mar 10;434(7030):225-9 PMID: 15759003
  17. Heat-evoked activation of the ion channel, TRPV4.
    J Neurosci. 2002 Aug 1;22(15):6408-14 PMID: 12151520
  18. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures.
    Cell. 2003 Mar 21;112(6):819-29 PMID: 12654248
  19. Central sensitization: a generator of pain hypersensitivity by central neural plasticity.
    J Pain. 2009 Sep;10(9):895-926 PMID: 19712899
  20. A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity.
    J Biol Chem. 2007 May 18;282(20):14975-83 PMID: 17355971
  21. Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures.
    Nature. 2007 Jun 14;447(7146):855-8 PMID: 17568746
  22. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons.
    Cell. 2001 Sep 7;106(5):619-32 PMID: 11551509
  23. Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma.
    Science. 1997 Oct 10;278(5336):279-83 PMID: 9323205
  24. Molecular genetics of migraine.
    Hum Genet. 2009 Jul;126(1):115-32 PMID: 19455354
  25. The menthol receptor TRPM8 is the principal detector of environmental cold.
    Nature. 2007 Jul 12;448(7150):204-8 PMID: 17538622
  26. Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding.
    J Clin Invest. 2007 Nov;117(11):3453-62 PMID: 17948126
  27. Intrathecal ziconotide for neuropathic pain: a review.
    Pain Pract. 2009 Sep-Oct;9(5):327-37 PMID: 19682321
  28. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.
    J Med Genet. 2004 Mar;41(3):171-4 PMID: 14985375
  29. Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1.
    Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12045-50 PMID: 18687886
  30. Distinct mechanosensitive properties of capsaicin-sensitive and -insensitive sensory neurons.
    J Neurosci. 2002 Jun 15;22(12):RC228 PMID: 12045233
  31. Neuropathic pain develops normally in mice lacking both Na(v)1.7 and Na(v)1.8.
    Mol Pain. 2005 Aug 22;1:24 PMID: 16111501
  32. Role of voltage-gated calcium channels in ascending pain pathways.
    Brain Res Rev. 2009 Apr;60(1):84-9 PMID: 19162069
  33. Glycine inhibitory dysfunction turns touch into pain through PKCgamma interneurons.
    PLoS One. 2007 Nov 07;2(11):e1116 PMID: 17987109
  34. Cutaneous nociception evoked by 15-delta PGJ2 via activation of ion channel TRPA1.
    Mol Pain. 2008 Jul 31;4:30 PMID: 18671867
  35. Innocuous, not noxious, input activates PKCgamma interneurons of the spinal dorsal horn via myelinated afferent fibers.
    J Neurosci. 2008 Aug 6;28(32):7936-44 PMID: 18685019
  36. Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain.
    J Pain. 2005 Jul;6(7):434-8 PMID: 15993821
  37. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury.
    Nature. 2003 Aug 14;424(6950):778-83 PMID: 12917686
  38. Chronic pain and medullary descending facilitation.
    Trends Neurosci. 2002 Jun;25(6):319-25 PMID: 12086751
  39. Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain.
    J Neurosci. 2005 Jul 13;25(28):6658-66 PMID: 16014727
  40. Role of the CX3CR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine.
    Brain Behav Immun. 2007 Jul;21(5):642-51 PMID: 17174525
  41. Dissociation of the opioid receptor mechanisms that control mechanical and heat pain.
    Cell. 2009 Jun 12;137(6):1148-59 PMID: 19524516
  42. Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade.
    Neuron. 2003 Jan 9;37(1):75-84 PMID: 12526774
  43. Knockout of the ASIC2 channel in mice does not impair cutaneous mechanosensation, visceral mechanonociception and hearing.
    J Physiol. 2004 Jul 15;558(Pt 2):659-69 PMID: 15169849
  44. TRPV1 unlike TRPV2 is restricted to a subset of mechanically insensitive cutaneous nociceptors responding to heat.
    J Pain. 2008 Apr;9(4):298-308 PMID: 18226966
  45. The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.
    Nat Neurosci. 1999 Jun;2(6):541-8 PMID: 10448219
  46. P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain.
    J Neurosci. 2008 Mar 12;28(11):2892-902 PMID: 18337420
  47. Ideas about pain, a historical view.
    Nat Rev Neurosci. 2007 Jan;8(1):71-80 PMID: 17180164
  48. Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain.
    Anesthesiology. 2002 May;96(5):1161-7 PMID: 11981157
  49. Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats.
    Eur J Neurosci. 2004 Nov;20(9):2294-302 PMID: 15525271
  50. Voltage-gated calcium channels in chronic pain: emerging role of alternative splicing.
    Pflugers Arch. 2008 Jun;456(3):459-66 PMID: 18389277
  51. Understanding sensory nerve mechanotransduction through localized elastomeric matrix control.
    PLoS One. 2009;4(1):e4293 PMID: 19173000
  52. Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress.
    J Neurosci. 2008 Mar 5;28(10):2485-94 PMID: 18322093
  53. Radial stretch reveals distinct populations of mechanosensitive mammalian somatosensory neurons.
    Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):20015-20 PMID: 19060212
  54. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.
    Neuron. 2004 Mar 25;41(6):849-57 PMID: 15046718
  55. Bimodal action of menthol on the transient receptor potential channel TRPA1.
    J Neurosci. 2007 Sep 12;27(37):9874-84 PMID: 17855602
  56. Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control.
    Physiology (Bethesda). 2008 Dec;23:360-70 PMID: 19074743
  57. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition.
    Mol Pain. 2007 Dec 17;3:40 PMID: 18086313
  58. A stomatin-domain protein essential for touch sensation in the mouse.
    Nature. 2007 Jan 11;445(7124):206-9 PMID: 17167420
  59. Transmission of chronic nociception by spinal neurons expressing the substance P receptor.
    Science. 1999 Nov 19;286(5444):1558-61 PMID: 10567262
  60. Abnormal osmotic regulation in trpv4-/- mice.
    Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13698-703 PMID: 14581612
  61. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.
    Cell. 2000 Oct 27;103(3):525-35 PMID: 11081638
  62. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction.
    Neuron. 2006 Apr 20;50(2):277-89 PMID: 16630838
  63. Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain.
    Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12706-11 PMID: 15314237
  64. Mechanosensitive currents in the neurites of cultured mouse sensory neurones.
    J Physiol. 2006 Dec 15;577(Pt 3):815-28 PMID: 17038434
  65. Evidence for a central component of post-injury pain hypersensitivity.
    Nature. 1983 Dec 15-21;306(5944):686-8 PMID: 6656869
  66. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain.
    Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10655-60 PMID: 17551020
  67. TRP channel activation by reversible covalent modification.
    Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19564-8 PMID: 17164327
  68. The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception.
    EMBO J. 2009 May 6;28(9):1308-18 PMID: 19279663
  69. A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino) methyl]amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat.
    J Pharmacol Exp Ther. 2006 Dec;319(3):1376-85 PMID: 16982702
  70. General anesthetics activate a nociceptive ion channel to enhance pain and inflammation.
    Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8784-9 PMID: 18574153
  71. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.
    Nature. 2000 May 11;405(6783):183-7 PMID: 10821274
  72. Tackling pain at the source: new ideas about nociceptors.
    Neuron. 1998 Apr;20(4):629-32 PMID: 9581756
  73. Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice.
    J Physiol. 2007 Feb 1;578(Pt 3):715-33 PMID: 17124270
  74. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin.
    Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15435-9 PMID: 8986829
  75. The cloned capsaicin receptor integrates multiple pain-producing stimuli.
    Neuron. 1998 Sep;21(3):531-43 PMID: 9768840
  76. Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4-/- mice.
    Mol Pain. 2007 Oct 29;3:31 PMID: 17967183
  77. Mechanosensitive whole-cell currents in cultured rat somatosensory neurons.
    Brain Res. 2000 Jun 30;869(1-2):225-30 PMID: 10865079
  78. Functional role of unmyelinated tactile afferents in human hairy skin: sympathetic response and perceptual localization.
    Exp Brain Res. 2008 Jan;184(1):135-40 PMID: 17962926
  79. Neural KCNQ (Kv7) channels.
    Br J Pharmacol. 2009 Apr;156(8):1185-95 PMID: 19298256
  80. The mammalian sodium channel BNC1 is required for normal touch sensation.
    Nature. 2000 Oct 26;407(6807):1007-11 PMID: 11069180
  81. The capsaicin receptor: a heat-activated ion channel in the pain pathway.
    Nature. 1997 Oct 23;389(6653):816-24 PMID: 9349813
  82. Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons.
    Nat Neurosci. 2001 Sep;4(9):869-70 PMID: 11528414
  83. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain.
    Nature. 2005 Dec 15;438(7070):1017-21 PMID: 16355225
  84. Novel class of pain drugs based on antagonism of NGF.
    Trends Pharmacol Sci. 2006 Feb;27(2):85-91 PMID: 16376998
  85. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.
    Nature. 2004 Jan 15;427(6971):260-5 PMID: 14712238
  86. Mechanosensitive ion channels in cultured sensory neurons of neonatal rats.
    J Neurosci. 2002 Feb 15;22(4):1238-47 PMID: 11850451
  87. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice.
    Neuron. 2001 Dec 20;32(6):1071-83 PMID: 11754838
  88. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.
    Nature. 2001 Jun 21;411(6840):957-62 PMID: 11418861
  89. Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing.
    J Neurosci. 2005 Apr 20;25(16):4052-61 PMID: 15843607
  90. Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury.
    J Neurochem. 2008 Jun 1;105(6):2249-59 PMID: 18363823
  91. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma.
    Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9099-104 PMID: 19458046
  92. Molecular mechanisms of nociception.
    Nature. 2001 Sep 13;413(6852):203-10 PMID: 11557989
  93. Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain.
    J Neurosci. 2008 Oct 29;28(44):11263-8 PMID: 18971468
  94. Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels.
    Nat Neurosci. 2008 Jul;11(7):772-9 PMID: 18568022
  95. Ionotropic and metabotropic receptors, protein kinase A, protein kinase C, and Src contribute to C-fiber-induced ERK activation and cAMP response element-binding protein phosphorylation in dorsal horn neurons, leading to central sensitization.
    J Neurosci. 2004 Sep 22;24(38):8310-21 PMID: 15385614
  96. The cell and molecular basis of mechanical, cold, and inflammatory pain.
    Science. 2008 Aug 1;321(5889):702-5 PMID: 18669863
  97. Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels.
    Trends Pharmacol Sci. 2007 May;28(5):220-8 PMID: 17403543
  98. Noxious heat activates all capsaicin-sensitive and also a sub-population of capsaicin-insensitive dorsal root ganglion neurons.
    Neuroscience. 1999;88(4):995-7 PMID: 10336113
  99. Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia.
    Pain. 2009 Mar;142(1-2):27-35 PMID: 19135797
  100. Neurosensory mechanotransduction.
    Nat Rev Mol Cell Biol. 2009 Jan;10(1):44-52 PMID: 19197331
  101. Human brain mechanisms of pain perception and regulation in health and disease.
    Eur J Pain. 2005 Aug;9(4):463-84 PMID: 15979027
  102. Upregulation of dorsal root ganglion (alpha)2(delta) calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats.
    J Neurosci. 2001 Mar 15;21(6):1868-75 PMID: 11245671
  103. Heat sensitization in skin and muscle nociceptors expressing distinct combinations of TRPV1 and TRPV2 protein.
    J Neurophysiol. 2007 Apr;97(4):2651-62 PMID: 17287441
  104. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines.
    Nature. 2007 Feb 1;445(7127):541-5 PMID: 17237762
  105. Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation.
    Nature. 1992 Apr 9;356(6369):521-3 PMID: 1373227
  106. Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex.
    Nat Med. 2008 Dec;14(12):1325-32 PMID: 19011637
  107. TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP.
    Pflugers Arch. 2009 Oct;458(6):1093-102 PMID: 19669158
  108. Alkylamides that produce tingling paresthesia activate tactile and thermal trigeminal neurons.
    Brain Res. 1999 Sep 25;842(2):452-60 PMID: 10526142
  109. Mechanisms of sensory transduction in the skin.
    Nature. 2007 Feb 22;445(7130):858-65 PMID: 17314972
  110. Glia in pathological pain: a role for fractalkine.
    J Neuroimmunol. 2008 Jul 31;198(1-2):113-20 PMID: 18547654
  111. TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones.
    J Physiol. 2007 Dec 15;585(Pt 3):867-79 PMID: 17962323
  112. TRPM8 is required for cold sensation in mice.
    Neuron. 2007 May 3;54(3):371-8 PMID: 17481391
  113. Identification of a cold receptor reveals a general role for TRP channels in thermosensation.
    Nature. 2002 Mar 7;416(6876):52-8 PMID: 11882888
  114. The effect of menthol on the thermoreceptors.
    Acta Physiol Scand. 1951 Oct 9;24(1):27-34 PMID: 14877581
  115. Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists.
    Pain. 1989 Apr;37(1):111-123 PMID: 2542867
  116. A capsaicin-receptor homologue with a high threshold for noxious heat.
    Nature. 1999 Apr 1;398(6726):436-41 PMID: 10201375
  117. Coexpression of heat-evoked and capsaicin-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons.
    Neurosci Lett. 1997 Aug 1;231(1):33-6 PMID: 9280161
  118. Novel classes of responsive and unresponsive C nociceptors in human skin.
    J Neurosci. 1995 Jan;15(1 Pt 1):333-41 PMID: 7823139
  119. A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators.
    J Neurosci. 2006 Apr 5;26(14):3864-74 PMID: 16597741
  120. A high-threshold heat-activated channel in cultured rat dorsal root ganglion neurons resembles TRPV2 and is blocked by gadolinium.
    Eur J Neurosci. 2007 Jul;26(1):12-22 PMID: 17596195
  121. A novel mechanosensitive channel identified in sensory neurons.
    Eur J Neurosci. 2006 May;23(10):2543-50 PMID: 16817857
  122. TRPA1 is differentially modulated by the amphipathic molecules trinitrophenol and chlorpromazine.
    J Biol Chem. 2007 Mar 9;282(10):7145-53 PMID: 17218316
  123. TRPA1 acts as a cold sensor in vitro and in vivo.
    Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1273-8 PMID: 19144922
  124. Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
    Science. 2000 Apr 14;288(5464):306-13 PMID: 10764638
  125. Attenuated cold sensitivity in TRPM8 null mice.
    Neuron. 2007 May 3;54(3):379-86 PMID: 17481392
  126. Caenorhabditis elegans TRPA-1 functions in mechanosensation.
    Nat Neurosci. 2007 May;10(5):568-77 PMID: 17450139
  127. A heat-sensitive TRP channel expressed in keratinocytes.
    Science. 2002 Jun 14;296(5575):2046-9 PMID: 12016205
  128. Sodium channel blockade may contribute to the analgesic efficacy of antidepressants.
    J Pain. 2007 Apr;8(4):315-24 PMID: 17175203
  129. Warm temperatures activate TRPV4 in mouse 308 keratinocytes.
    J Biol Chem. 2003 Aug 22;278(34):32037-46 PMID: 12783886
  130. The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures.
    J Biol Chem. 2009 Aug 7;284(32):21257-64 PMID: 19531473
  131. Reversal of pathological pain through specific spinal GABAA receptor subtypes.
    Nature. 2008 Jan 17;451(7176):330-4 PMID: 18202657
  132. Genetics and molecular pathophysiology of Na(v)1.7-related pain syndromes.
    Adv Genet. 2008;63:85-110 PMID: 19185186
  133. Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain.
    Pain. 2005 Apr;114(3):386-396 PMID: 15777864
  134. Specificity of cold thermotransduction is determined by differential ionic channel expression.
    Nat Neurosci. 2002 Mar;5(3):254-60 PMID: 11836533
  135. Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions.
    Eur J Neurosci. 2004 Sep;20(5):1150-60 PMID: 15341587
  136. NaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders.
    J Neurosci. 2008 Oct 22;28(43):11079-88 PMID: 18945915
  137. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy.
    Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5856-61 PMID: 15809417
  138. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
    Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13519-24 PMID: 17684094
  139. An SCN9A channelopathy causes congenital inability to experience pain.
    Nature. 2006 Dec 14;444(7121):894-8 PMID: 17167479
  140. Myelinated afferents signal the hyperalgesia associated with nerve injury.
    Pain. 1988 Jan;32(1):89-94 PMID: 3340426
  141. Transformation of the output of spinal lamina I neurons after nerve injury and microglia stimulation underlying neuropathic pain.
    Mol Pain. 2007 Sep 27;3:27 PMID: 17900333
  142. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord.
    J Neurosci. 2002 Aug 1;22(15):6724-31 PMID: 12151551
  143. P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury.
    J Neurosci. 2008 May 7;28(19):4949-56 PMID: 18463248
  144. Disinhibition opens the gate to pathological pain signaling in superficial neurokinin 1 receptor-expressing neurons in rat spinal cord.
    J Neurosci. 2006 Feb 8;26(6):1833-43 PMID: 16467532
  145. Neurotrophins and their receptors: a convergence point for many signalling pathways.
    Nat Rev Neurosci. 2003 Apr;4(4):299-309 PMID: 12671646
  146. Variable threshold of trigeminal cold-thermosensitive neurons is determined by a balance between TRPM8 and Kv1 potassium channels.
    J Neurosci. 2009 Mar 11;29(10):3120-31 PMID: 19279249
  147. In vivo silencing of the Ca(V)3.2 T-type calcium channels in sensory neurons alleviates hyperalgesia in rats with streptozocin-induced diabetic neuropathy.
    Pain. 2009 Sep;145(1-2):184-95 PMID: 19577366
  148. The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function.
    Gastroenterology. 2004 Dec;127(6):1739-47 PMID: 15578512
  149. The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord.
    J Neurophysiol. 1994 Jul;72(1):169-79 PMID: 7965003
  150. Pain mechanisms: a new theory.
    Science. 1965 Nov 19;150(3699):971-9 PMID: 5320816
  151. Autoimmunity and anti-TNF-alpha agents.
    Ann N Y Acad Sci. 2005 Jun;1051:559-69 PMID: 16126996
  152. Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones.
    J Physiol. 2004 May 1;556(Pt 3):691-710 PMID: 14990679
  153. Physiology. Cold current in thermoreceptive neurons.
    Nature. 2001 Oct 4;413(6855):480 PMID: 11586349
  154. The P2Y12 receptor regulates microglial activation by extracellular nucleotides.
    Nat Neurosci. 2006 Dec;9(12):1512-9 PMID: 17115040
  155. GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization.
    Science. 2004 May 7;304(5672):884-7 PMID: 15131310
  156. Pungent qualities of sanshool-related compounds evaluated by a sensory test and activation of rat TRPV1.
    Biosci Biotechnol Biochem. 2005 Oct;69(10):1951-7 PMID: 16244447
  157. Nociceptors lacking TRPV1 and TRPV2 have normal heat responses.
    J Neurosci. 2004 Jul 14;24(28):6410-5 PMID: 15254097
  158. Long-term potentiation at C-fibre synapses by low-level presynaptic activity in vivo.
    Mol Pain. 2008 May 28;4:18 PMID: 18507818
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.09.028
Email
[email protected]
Published
2009-10-16
Pages
267-84
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2852643
Subset
IM
Grants
NINDS NIH HHS · R37 NS047723-16 · United States
NINDS NIH HHS · R37 NS047723-15 · United States
NINDS NIH HHS · R37 NS047723-18 · United States
NINDS NIH HHS · R01 NS055299-03 · United States
NINDS NIH HHS · R01 NS055299-01 · United States
NINDS NIH HHS · R37 NS047723-17 · United States
NINDS NIH HHS · R01 NS055299-04 · United States
NINDS NIH HHS · R01 NS055299 · United States
NINDS NIH HHS · R37 NS047723-13 · United States
NINDS NIH HHS · R37 NS047723 · United States
NINDS NIH HHS · R37 NS047723-14 · United States
NINDS NIH HHS · R01 NS055299-02 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2009.09.028 PMC Full Text View journal details
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