Experimental Brain Research

, Volume 196, Issue 1, pp 153–162 | Cite as

Joint pain

  • Hans-Georg SchaibleEmail author
  • Frank Richter
  • Andrea Ebersberger
  • Michael K. Boettger
  • Horacio Vanegas
  • Gabriel Natura
  • Enrique Vazquez
  • Gisela Segond von Banchet


Both inflammatory and degenerative diseases of joints are major causes of chronic pain. This overview addresses the clinical problem of joint pain, the nociceptive system of the joint, the mechanisms of peripheral and central sensitization during joint inflammation and long term changes during chronic joint inflammation. While the nature of inflammatory pain is obvious the nature and site of origin of osteoarthritic pain is less clear. However, in both pathological conditions mechanical hyperalgesia is the major pain problem, and indeed, both joint nociceptors and spinal nociceptive neurons with joint input show pronounced sensitization for mechanical stimulation. Molecular mechanisms of mechanical sensitization of joint nociceptors are addressed with an emphasis on cytokines, and molecular mechanisms of central sensitization include data on the role of excitatory amino acids, neuropeptides and spinal prostaglandins. The overview will also address long-term changes of pain-related behavior, response properties of neurons and receptor expression in chronic animal models of arthritis.


Arthritis Osteoarthritis Cytokines Central sensitization Peripheral sensitization 


  1. Amaya F, Oh-Hashi K, Naruse Y, Iijima N, Ueda M, Shimosato G, Tominaga Y, Tanaka Y, Tanaka M (2003) Local inflammation increases vanilloid receptor 1 expression within distinct subgroups of DRG neurons. Brain Res 963:190–196PubMedCrossRefGoogle Scholar
  2. Arendt-Nielsen L, Laursen RJ, Drewes AM (2000) Referred pain as an indicator for neural plasticity. In: Sandkühler J, Bromm B, Gebhart GF (eds) Prog Brain Res, vol 129. Elsevier, Amsterdam, pp 343–356Google Scholar
  3. Arvidson NG, Gudbjornsson B, Elfman L, Ryden AC, Tötterman TH, Hällgren R (1994) Circadian rhythms of serum interleukin-6 in rheumatoid arthritis. Rheum Dis 53:521–524CrossRefGoogle Scholar
  4. Attur MG, Dave M, Akamatsu M, Katoh M, Amin AR (2002) Osteoarthritis or osteoarthrosis: the definition of inflammation becomes a semantic issue in the genomic era of molecular medicine. Osteoarthr Cartil 10:1–4PubMedCrossRefGoogle Scholar
  5. Bajaj P, Bajaj P, Graven-Nielsen T, Arendt-Nielsen L (2001) Osteoarthritis and its association with muscle hyperalgesia: an experimental controlled study. Pain 93:107–114PubMedCrossRefGoogle Scholar
  6. Bär K-J, Natura G, Telleria-Diaz A, Teschner P, Vogel R, Vasquez E, Schaible H-G, Ebersberger A (2004a) Changes in the effect of spinal prostaglandin E2 during inflammation—prostaglandin E (EP1–EP4) receptors in spinal nociceptive processing of input from the normal or inflamed knee joint. J Neurosci 24:642–651PubMedCrossRefGoogle Scholar
  7. Bär K-J, Schurigt U, Scholze A, Segond von Banchet G, Stopfel N, Bräuer R, Halbhuber K-J, Schaible H-G (2004b) The expression and localisation of somatostatin receptors in dorsal root ganglion neurons of normal and monoarthritic rats. Neuroscience 127:197–206PubMedCrossRefGoogle Scholar
  8. Bär K-J, Schaible H-G, Bräuer R, Halbhuber K-J, Segond von Banchet G (2004c) The proportion of TRPV1 protein-positive lumbar DRG neurones does not increase in the course of acute and chronic antigen-induced arthritis in the knee joint of the rat. Neurosci Lett 361:172–175PubMedCrossRefGoogle Scholar
  9. Barnes PJ, Karin M (1997) Nuclear factor-κB—a pivotal transcription factor in chronic inflammatory diseases. New Engl J Med 336:1066–1071PubMedCrossRefGoogle Scholar
  10. Boettger MK, Hensellek S, Richter F, Gajda M, Stoeckigt R, Segond von Banchet G, Braeuer R, Schaible H-G (2008) Antinociceptive effects of TNF-α neutralization in a rat model of antigen-induced arthritis. Arthritis Rheum 58:2368–2378PubMedCrossRefGoogle Scholar
  11. Breivik H, Beverly C, Ventafridda V, Cohen R, Gallacher D (2006) Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 10:287–333PubMedCrossRefGoogle Scholar
  12. Brenn D, Richter F, Schaible H-G (2007) Sensitization of unmyelinated sensory fibres of the joint nerve to mechanical stimuli by interleukin-6 in the rat. An inflammatory mechanism of joint pain. Arthritis Rheum 56:351–359PubMedCrossRefGoogle Scholar
  13. Calvino B, Villanueva L, LeBars D (1987) Dorsal horn (convergent) neurones in the intact anaesthetized arthritic rat. II. Heterotopic inhibitory influences. Pain 31:359–379PubMedCrossRefGoogle Scholar
  14. Carlton SM, Coggeshall RE (2001) Peripheral capsaicin receptors increase in the inflamed rat hindpaw: a possible mechanism for peripheral sensitization. Neurosci Lett 310:53–56PubMedCrossRefGoogle Scholar
  15. Carlton SM, Du J, Zhou S, Coggeshall RE (2001) Tonic control of peripheral cutaneous nociceptors by somatostatin receptors. J Neurosci 21:4042–4049PubMedGoogle Scholar
  16. Cervero F, Schaible H-G, Schmidt RF (1991) Tonic descending inhibition of spinal cord neurones driven by joint afferents in normal cats and in cats with an inflamed knee joint. Exp Brain Res 83:675–678PubMedCrossRefGoogle Scholar
  17. Chen L-W, Egan L, Li Z-W, Greten FR, Kagnoff MF, Karin M (2003) The two faces of IKK and NF-κB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med 9:575–581PubMedCrossRefGoogle Scholar
  18. Craig AD, Heppelmann B, Schaible H-G (1988) The projection of the medial and posterior articular nerves of the cat’s knee to the spinal cord. J Comp Neurol 276:279–288PubMedCrossRefGoogle Scholar
  19. De Benedetti F, Massa M, Pignatti P, Albani S, Novick D, Martini A (1994) Serum soluble interleukin-6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 93:2114–2119PubMedCrossRefGoogle Scholar
  20. Desgeorges A, Gabay C, Silacci P, Novick D, Roux-Lombard P, Grau G, Dayer JM, Vischer T, Guerne PA (1997) Concentrations and origins of soluble interleukin 6 receptor in serum and synovial fluid. J Rheumatol 24:1510–1516PubMedGoogle Scholar
  21. Dina OA, Green PG, Levine JD (2008) Role of interleukin-6 in chronic muscle hyperalgesic priming. Neuroscience 152:521–525PubMedCrossRefGoogle Scholar
  22. Dong WK, Ryu H, Wagman IH (1978) Nociceptive responses of neurons in medial thalamus and their relationship to spinothalamic pathways. J Neurophysiol 41:1592–1613PubMedGoogle Scholar
  23. Dorn T, Schaible H-G, Schmidt RF (1991) Response properties of thick myelinated group II afferents in the medial articular nerve of normal and inflamed knee joints of the cat. Somatosens Mot Res 8:127–136PubMedCrossRefGoogle Scholar
  24. Dye SF, Vaupel GL, Dye CC (1998) Conscious neurosensory mapping of the internal structures of the human knee without intraarticular anesthesia. Am J Sports Med 26:773–777PubMedGoogle Scholar
  25. Ebersberger A, Grubb BD, Willingale HL, Gardiner NJ, Nebe J, Schaible H-G (1999) The intraspinal release of prostaglandin E2 in a model of acute arthritis is accompanied by an upregulation of cyclooxygenase-2 in the rat spinal cord. Neuroscience 93:775–781PubMedCrossRefGoogle Scholar
  26. Ebersberger A, Buchmann M, Ritzeler O, Michaelis M, Schaible H-G (2006) The role of spinal nuclear factor-κB in spinal hyperexcitability. Neuroreport 17:1615–1618PubMedCrossRefGoogle Scholar
  27. Feldmann M, Maini RN (2001) Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Ann Rev Immunol 19:163–196CrossRefGoogle Scholar
  28. Felson DT (2005) The sources of pain in knee osteoarthritis. Curr Opin Rheumatol 17:624–628PubMedCrossRefGoogle Scholar
  29. Fields HL, Clanton CH, Anderson SD (1977) Somatosensory properties of spinoreticular neurons in the cat. Brain Res 120:49–66PubMedCrossRefGoogle Scholar
  30. Flake NM, Gold MS (2005) Inflammation alters sodium currents and excitability of temporomandibular joint afferents. Neurosci Lett 384:294–299PubMedCrossRefGoogle Scholar
  31. Gautron M, Guilbaud G (1982) Somatic responses of ventrobasal thalamic neurones in polyarthritic rats. Brain Res 237:459–471PubMedCrossRefGoogle Scholar
  32. Griffiths RJ (1992) Characterisation and pharmacological sensitivity of antigen arthritis induced by methylated bovine serum albumin in the rat. Agents Actions 35:88–95PubMedCrossRefGoogle Scholar
  33. Grigg P, Schaible H-G, Schmidt RF (1986) Mechanical sensitivity of group III and IV afferents from posterior articular nerve in normal and inflamed cat knee. J Neurophysiol 55:635–643PubMedGoogle Scholar
  34. Grill M, Heinemann A, Hoefler G, Perkar BA, Schuligoi R (2008) Effect of endotoxin treatment on the expression and localization of spinal cyclooxygenase, prostaglandin synthases, and PGD2 receptors. J Neurochem 104:1345–1357PubMedCrossRefGoogle Scholar
  35. Grubb BD, Stiller RU, Schaible H-G (1993) Dynamic changes in the receptive field properties of spinal cord neurons with ankleinput in rats with unilateral adjuvant-induced inflammation in the ankle region. Exp Brain Res 92:441–452PubMedCrossRefGoogle Scholar
  36. Guilbaud G, Caille D, Besson J-M, Benelli G (1977) Single unit activities in ventral posterior and posterior group thalamic nuclei during nociceptive and non nociceptive stimulations in the cat. Arch Ital Biol 15:38–56Google Scholar
  37. Guilbaud G, Peschanski M, Gautron M (1980) Neurones responding to noxious stimulation in VB complex and caudal adjacent regions in the thalamus of the rat. Pain 8:303–318PubMedCrossRefGoogle Scholar
  38. Guilbaud G, Iggo A, Tegner R (1985) Sensory receptors in ankle joint capsules of normal and arthritic rats. Exp Brain Res 58:29–40Google Scholar
  39. Han JS, Li W, Neugebauer V (2005) Critical role of calcitonin gene-related peptide 1 receptors in the amygdala in synaptic plasticity and pain behaviour. J Neurosci 25:10717–10728PubMedCrossRefGoogle Scholar
  40. Helyes Z, Szabó A, Németh J, Jakab B, Pintér E, Bánvölgyi Á, Kereskai L, Kéri G, Szolcsányi J (2004) Antiinflammatory and analgesic effects of somatostatin released from capsaicin-sensitive sensory nerve terminals in a Freund’s adjuvant-induced chronic arthritis model in the rat. Arthritis Rheum 50:1677–1685PubMedCrossRefGoogle Scholar
  41. Heppelmann B, Pawlak M (1997) Inhibitory effect of somatostatin on the mechanosensitivity of articular afferents in normal and inflamed knee joints of the rat. Pain 73:377–382PubMedCrossRefGoogle Scholar
  42. Heppelmann B, Pawlak M (1999) Peripheral application of cyclo-somatostatin, a somatostatin antagonist, increases the mechanosensitivity of the knee joint afferents. Neurosci Lett 259:62–64PubMedCrossRefGoogle Scholar
  43. Heppelmann B, Pawlak M, Just S, Schmidt RF (2001) Cortical projection of the rat knee joint innervation and its processing in the somatosensory areas SI and SII. Exp Brain Res 141:501–506PubMedCrossRefGoogle Scholar
  44. Hutchison WD, Lühn MA, Schmidt RF (1992) Knee joint input into the peripheral region of the ventral posterior lateral nucleus of cat thalamus. J Neurophysiol 67:1092–1104PubMedGoogle Scholar
  45. Hutchison WD, Lühn MAB, Schmidt RF (1994) Responses of lateral thalamic neurons to algesic stimulation of the cat knee joint. Exp Brain Res 101:452–454PubMedCrossRefGoogle Scholar
  46. Inglis JJ, Notley CA, Essex D, Wilson AW, Feldmann M, Anand P, Williams R (2007) Collagen-induced arthritis as a model of hyperalgesia. Functional and cellular analysis of the analgesic actions of tumor necrosis factor blockade. Arthritis Rheum 56:4015–4023PubMedCrossRefGoogle Scholar
  47. Ji G, Neugebauer V (2007) Differential effects of CRF1 and CRF2 receptor antagonists on pain-related sensitization of neurons in the central nucleus of the amygdala. J Neurophysiol 97:3893–3904PubMedCrossRefGoogle Scholar
  48. Ji R-R, Samad TA, Jin SX, Schmoll R, Woolf CJ (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36:57–68PubMedCrossRefGoogle Scholar
  49. Kamimura D, Ishihara K, Hirano T (2003) IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol 149:1–38PubMedCrossRefGoogle Scholar
  50. Kellgren JH (1939) Some painful joint conditions and their relation to osteoarthritis. Clin Sci 4:193–205Google Scholar
  51. Kellgren JH, Samuel EP (1950) The sensitivity and innervation of the articular capsule. J Bone Joint Surg 4:193–205Google Scholar
  52. Krauspe R, Schmidt M, Schaible H-G (1992) Sensory innervation of the anterior cruciate ligament: an electrophysiological study of the response properties of single identified mechanoreceptors in the cat. J Joint Bone Surg 7:390–397Google Scholar
  53. Lamour Y, Willer JC, Guilbaud G (1983a) Rat somatosensory (Sm I) cortex. I. Characteristics of neuronal responses to noxious simulation and comparison with responses to non-noxious stimulation. Exp Brain Res 49:35–45PubMedGoogle Scholar
  54. Lamour Y, Willer JC, Guilbaud G (1983b) Rat somatosensory (Sm I) cortex. II. Laminar and columnar organization of noxious and non-noxious inputs. Exp Brain Res 49:46–54PubMedGoogle Scholar
  55. Lamour Y, Willer JC, Guilbaud G (1983c) Altered properties and laminar distribution of neuronal responses to peripheral stimulation in the Sm I cortex of the arthritic rat. Brain Res 273:183–187PubMedCrossRefGoogle Scholar
  56. Lee KM, Kang BS, Lee HL, Son SJ, Hwang SH, Kim DS, Par J-S, Cho H-J (2004) Spinal NF-κB activation induces COX-2 upregulation and contributes to inflammatory pain hypersensitivity. Eur J NeuroSci 19:3375–3381PubMedCrossRefGoogle Scholar
  57. Lewis T (1938) Suggestions relating to the study of somatic pain. Br Med J 1:321–325CrossRefGoogle Scholar
  58. Lewis T (1942) Pain. McMilan, LondonGoogle Scholar
  59. Li W, Neugebauer V (2004) Block of NMDA and non-NMDA receptor activation results in reduced background and evoked activity of central amygdala neurons in a model of arthritic pain. Pain 110:112–122PubMedCrossRefGoogle Scholar
  60. Liang X, Wu L, Hand T, Andreasson K (2005) Prostaglandin D2 mediates neuronal protection via the DP1 receptor. J Neurochem 92:477–486PubMedCrossRefGoogle Scholar
  61. Martindale JC, Wilson AW, Reeve AJ, Chessell IP, Headley PM (2007) Chronic secondary hypersensitivity of dorsal horn neurones following inflammation of the knee joint. Pain 133:79–86PubMedCrossRefGoogle Scholar
  62. Maunz RA, Pitts NG, Peterson BW (1978) Cat spinoreticular neurones: locations, responses and changes in responses during repetitive stimulation. Brain Res 148:365–379PubMedCrossRefGoogle Scholar
  63. McDougall J (2006) Arthritis and pain: neurogenic origin of joint pain. Arthritis Res Ther 8:220–229PubMedCrossRefGoogle Scholar
  64. Menetréy D, Besson J-M (1982) Electrophysiological characteristics of dorsal horn cells in rats with cutaneous inflammation resulting from chronic arthritis. Pain 13:343–364PubMedCrossRefGoogle Scholar
  65. Menetréy D, Gannon JD, Levine JD, Basbaum AI (1989) Expression of c-fos protein in interneurons and projection neurons of the rat spinal cord in response to noxious somatic, articular, and visceral stimulation. J Comp Neurol 285:177–195PubMedCrossRefGoogle Scholar
  66. Meyers DER, Snow PJ (1982) The responses to somatic stimuli of deep spinothalamic tract cells in the lumbar spinal cord of the cat. J Physiol 329:355–371PubMedGoogle Scholar
  67. Milenkovic N, Wetzel C, Moshourab R, Lewin GR (2008) Speed and temperature dependences of mechanotransduction in afferent fibers recorded from the mouse saphenous nerve. J Neurophysiol 100:2771–2783PubMedCrossRefGoogle Scholar
  68. Minami T, Okuda-Ashitaka E, Nishizawa M, Mori H, Ito S (1997) Inhibition of nociceptin-induced allodynia in conscious mice by prostaglandin D2. Br J Pharmacol 122:605–610PubMedCrossRefGoogle Scholar
  69. Neugebauer V, Schaible H-G (1990) Evidence for a central component in the sensitization of spinal neurons with joint input during development of acute arthritis in cat’s knee. J Neurophysiol 64:299–311PubMedGoogle Scholar
  70. Neugebauer V, Luecke T, Schaible H-G (1993) N-methyl-d-aspartate (NMDA) and non-NMDA receptor antagonists block the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat’s knee joint. J Neurophysiol 70:1365–1377PubMedGoogle Scholar
  71. Novick D, Engelmann H, Wallach D, Rubinstein M (1989) Soluble cytokine receptors are present in normal human urine. J Exp Med 170:1409–1414PubMedCrossRefGoogle Scholar
  72. Obreja O, Biasio W, Andratsch M, Lips KS, Rathee PK, Ludwig A, Rose-John S, Kress M (2005) Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons. Brain 128:1634–1641PubMedCrossRefGoogle Scholar
  73. Price DD, Greenspan JD, Dubner R (2003) Neurons involved in the exteroceptive function of pain. Pain 106:215–219PubMedCrossRefGoogle Scholar
  74. Roth A, Mollenhauer J, Wagner A, Fuhrmann R, Straub A, Venbrocks RA, Petrow P, Braeuer R, Schubert H, Ozegowski J, Peschel G, Mueller PJ, Kinne RW (2005) Intra-articular injections of high-molecular-weight hyaluronic acid have biphasic effects on joint inflammation and destruction in rat antigen-induced arthritis. Arthritis Res Ther 7:R677–R686PubMedCrossRefGoogle Scholar
  75. Sandkuehler J (2000) Learning and memory in pain pathways. Pain 88:113–118CrossRefGoogle Scholar
  76. Schaible H-G (2006) Basic mechanisms of deep somatic pain. In: McMahon SB, Koltzenburg M (eds) Wall and Melzack’s textbook of pain, 5th edn. Elsevier, Churchill, Livingston, London, pp 621–633Google Scholar
  77. Schaible H-G, Grubb BD (1993) Afferent and spinal mechanisms of joint pain. Pain 55:5–54PubMedCrossRefGoogle Scholar
  78. Schaible H-G, Schmidt RF (1983a) Responses of fine medial articular nerve afferents to passive movements of knee joint. J Neurophysiol 49:1118–1126PubMedGoogle Scholar
  79. Schaible H-G, Schmidt RF (1983b) Activation of groups III and IV sensory units in medial articular nerve by local mechanical stimulation of knee joint. J Neurophysiol 49:35–44PubMedGoogle Scholar
  80. Schaible H-G, Schmidt RF (1985) Effects of an experimental arthritis on the sensory properties of fine articular afferent units. J Neurophysiol 54:1109–1122PubMedGoogle Scholar
  81. Schaible H-G, Schmidt RF (1988) Time course of mechanosensitivity changes in articular afferents during a developing experimental arthritis. J Neurophysiol 60:2180–2195PubMedGoogle Scholar
  82. Schaible H-G, Schmidt RF, Willis WD (1986) Responses of spinal cord neurones to stimulation of articular afferent fibres in the cat. J Physiol 372:575–593PubMedGoogle Scholar
  83. Schaible H-G, Schmidt RF, Willis WD (1987a) Convergent inputs from articular, cutaneous and muscle receptors onto ascending tract cells in the cat spinal cord. Exp Brain Res 66:479–488PubMedCrossRefGoogle Scholar
  84. Schaible H-G, Schmidt RF, Willis WD (1987b) Enhancement of the responses of ascending tract cells in the cat spinal cord by acute inflammation of the knee joint. Exp Brain Res 66:489–499PubMedCrossRefGoogle Scholar
  85. Schaible H-G, Neugebauer V, Cervero F, Schmidt RF (1991) Changes in tonic descending inhibition of spinal neurons with articular input during the development of acute arthritis in the cat. J Neurophysiol 66:1021–1032PubMedGoogle Scholar
  86. Schaible H-G, Schmelz M, Tegeder I (2006) Pathophysiology and treatment of pain in joint disease. Adv Drug Deliv Rev 58:323–342PubMedCrossRefGoogle Scholar
  87. Scott DL (2006) Osteoarthritis and rheumatoid arthritis. In: McMahon SB, Koltzenburg M (eds) Wall and Melzack’s textbook of pain, 5th edn. Elsevier, London, pp 653–667Google Scholar
  88. Segond von Banchet G, Petrow PK, Braeuer R, Schaible H-G (2000) Monoarticular antigen- induced arthritis leads to pronounced bilateral upregulation of the expression of neurokinin 1 and bradykinin 2 receptors in dorsal root ganglion neurones of rats. Arthritis Res 2:424–427CrossRefGoogle Scholar
  89. Segond von Banchet G, Kiehl M, Schaible H-G (2005) Acute and long-term effects of interleukin-6 on cultured dorsal root ganglion neurones from adult rat. J Neurochem 94:238CrossRefGoogle Scholar
  90. Sharif Naeini R, Cahill CM, Ribeiro-da-Silva A, Ménard HA, Henry JL (2005) Remodelling of spinal nociceptive mechanisms in an animal model of monoarthritis. Eur J Neurosci 22:2005–2015PubMedCrossRefGoogle Scholar
  91. Sluka KA (2002) Stimulation of deep somatic tissue with capsaicin produces long-lasting mechanical allodynia and heat hypoalgesia that depends on early activation of the cAMP pathway. J Neurosci 22:5687–5693PubMedGoogle Scholar
  92. Sommer C, Kress M (2004) Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett 361:184–187PubMedCrossRefGoogle Scholar
  93. Straub RH, Cutolo M (2001) Involvement of the hypothalamic–pituitary–adrenal/gonadal axis and the peripheral nervous system in rheumatoid arthritis. Arthritis Rheum 44:493–507PubMedCrossRefGoogle Scholar
  94. Tegeder I, Niederberger E, Schmidt R, Kunz S, Gühring H, Ritzeler O, Michaelis M, Geisslinger G (2004) Specific inhibition of IκB kinase reduces hyperalgesia in inflammatory and neuropathic pain models in rats. J Neurosci 24:1637–1645PubMedCrossRefGoogle Scholar
  95. Telleria-Diaz A, Ebersberger A, Vasquez E, Schache F, Kahlenbach J, Schaible H-G (2008) Different effects of spinally applied prostaglandin D2 (PGD2) on responses of dorsal horn neurons with knee input in normal rats and in rats with acute knee inflammation. Neuroscience 156:184–192PubMedCrossRefGoogle Scholar
  96. Vasquez E, Bär K-J, Ebersberger A, Klein B, Vanegas H, Schaible H-G (2001) Spinal prostaglandins are involved in the development but not the maintenance of inflammation-induced spinal hyperexcitability. J Neurosci 21:9001–9008PubMedGoogle Scholar
  97. Willingale HL, Gardiner NJ, McLymont N, Giblett S, Grubb BD (1997) Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol 122:1593–1604PubMedCrossRefGoogle Scholar
  98. Woolf CJ, Wall PD (1986) Relative effectiveness of C primary afferent fibres of different origins in evoking a prolonged facilitation of the flexor reflex in the rat. J Neurosci 6:1433–1442PubMedGoogle Scholar
  99. Zhou Y, Li G-D, Zhao Z-Q (2003) State-dependent phosphorylation of ε-isozyme of protein kinase C in adult rat dorsal root ganglia after inflammation and nerve injury. J Neurochem 85:571–580PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Hans-Georg Schaible
    • 1
    Email author
  • Frank Richter
    • 1
  • Andrea Ebersberger
    • 1
  • Michael K. Boettger
    • 1
  • Horacio Vanegas
    • 1
  • Gabriel Natura
    • 1
  • Enrique Vazquez
    • 1
  • Gisela Segond von Banchet
    • 1
  1. 1.Institute of Physiology 1/NeurophysiologyUniversity Hospital JenaJenaGermany

Personalised recommendations