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Last data updates: 06 January 2011 Fang, M., Wang, Y., He, Q.H., Sun, Y.X., Deng, L.B., Wang, X.M. and Han, J.S. (2003), Glial cell line-derived neurotrophic factor contributes to delayed inflammatory hyperalgesia in adjuvant rat pain model. Neuroscience, 117 (3), 503-512. Document type: Article Language: English Cited references: 57 Time cited: 21 Times self cited: 0 Abstract: Neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor, are members of the structurally related neurotrophin family that play important roles in pain modulation. Although there are also indications for the involvement of glial cell line-derived neurotrophic factor (GDNF), it is unclear whether and how GDNF is involved in inflammatory pain. In the present study, we studied the expression pattern of GDNF in dorsal root ganglia (DRG) and spinal cord, using confocal microscopy. We demonstrate that GDNF is well associated with nonpeptidergic pain pathway and that GDNF could possibly be anterogradely transported from DRG neurons to superficial spinal cord dorsal horn. We also studied the dynamic changes of GDNF expression in rats during chronic inflammation using injection of complete Freund's adjuvant as a model of chronic pain. We found that GDNF was down-regulated in both dorsal root ganglia and spinal cords 2 weeks after arthritis induction. To assess the impact of this down-regulation on pain transmission, we used a function-blocking antibody against GDNF delivered intrathecally in the same chronic-pain animal models. Injection of this antibody to GDNF produced no immediate effect, but decreased the delayed, bilateral hyperalgesia induced from a unilateral injection of complete Freund's adjuvant. The effect of this antibody coincided with the downregulation of GDNF immunoreactivity in response to inflammation, suggesting that GDNF supports biochemical changes that contribute to hyperalgesia. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved. Author Keywords: GDNF; pain pathway; nociception; arthritis; IB4 Keywords Plus: Anterograde Axonal-Transport; Midbrain Dopaminergic-Neurons; Sensory Neurons; Primary Afferents; Spinal-Cord; Dorsal Horn; Substance-P; Immunocytochemical Localization; Nervous-System; Ganglion-Cells Reprint Address: Han, JS (reprint author), Peking Univ, Neurosci Res Inst, Hlth Sci Ctr, Beijing 100083, Peoples R China Addresses: 1. Peking Univ, Neurosci Res Inst, Hlth Sci Ctr, Beijing 100083, Peoples R China 1. 2. Vivoli, E., Mennelli, L.D., Salvicchi, A., Bartolini, A., Koverech, A., Nicolai, R., Benatti, P. and Ghelardini, C. (2010), Acetyl-L-Carnitine Increases Artemin Level and Prevents Neurotrophic Factor Alterations During Neuropathy. Neuroscience, 167 (4), 1168-1174. Lundborg, C., Hahn-Zoric, M., Biber, B. and Hansson, E. (2010), Glial cell line-derived neurotrophic factor is increased in cerebrospinal fluid but decreased in blood during long-term pain. Journal of Neuroimmunology, 220 (1-2), 108-113. 3. 4. 5. 6. Pedersen, L.M., Jacobsen, L.M., Mollerup, S. and Gjerstad, J. (2010), Spinal cord long-term potentiation (LTP) is associated with increased dorsal horn gene expression of IL-1 beta, GDNF and iNOS. European Journal of Pain, 14 (3), 255-260. Takeda, M., Kitagawa, J., Nasu, M., Takahashia, M., Iwata, K. and Matsumoto, S. (2010), Glial cell line-derived neurotrophic factor acutely modulates the excitability of rat small-diameter trigeminal ganglion neurons innervating facial skin. Brain Behavior and Immunity, 24 (1), 72-82. Ciobanu, C., Reid, G. and Babes, A. (2009), Acute and chronic effects of neurotrophic factors BDNF and GDNF on responses mediated by thermo-sensitive TRP channels in cultured rat dorsal root ganglion neurons. Brain Research, 1284, 54-67. Russell, F.A., Fernandes, E.S., Courade, J.P., Keeble, J.E. and Brain, S.D. (2009), Tumour necrosis factor alpha mediates transient receptor potential vanilloid 1-dependent bilateral thermal hyperalgesia with distinct peripheral roles of interleukin-1 beta, protein kinase C and 7. cyclooxygenase-2 signalling. Pain, 142 (3), 264-274. Sakai, A., Asada, M., Seno, N. and Suzuki, H. (2008), Involvement of neural cell adhesion molecule signaling in glial cell line-derived neurotrophic factor-induced analgesia in a rat 8. model of neuropathic pain. Pain, 137 (2), 378-388. Quintao, N.L.M., Santos, A.R.S., Campos, M.M. and Calixto, J.B. (2008), The role of neurotrophic factors in genesis and maintenance of mechanical hypernociception after brachial 9. plexus avulsion in mice. Pain, 136 (1-2), 125-133. Jongen, J.L.M., Jaarsma, D., Hossaini, M., Natarajan, D., Haasdijk, E.D. and Holstege, J.C. (2007), Distribution of RET immunoreactivity in the rodent spinal cord and changes after nerve injury. Journal of Comparative Neurology, 500 (6), 1136-1153. 10. Albers, K.M., Woodbury, C.J., Ritter, A.M., Davis, B.M. and Koerber, H.R. (2006), Glial cell line-derived neurotrophic factor expression in skin alters the mechanical sensitivity of cutaneous nociceptors. Journal of Neuroscience, 26 (11), 2981-2990. 11. Yang, H., Bernanke, J.M. and Naftel, J.P. (2006), Immunocytochemical evidence that most sensory neurons of the rat molar pulp express receptors for both glial cell line-derived neurotrophic factor and nerve growth factor. Archives of Oral Biology, 51 (1), 69-78. 12. Ambalavanar, R., Moritani, M. and Dessem, D. (2005), Trigeminal P2X(3) receptor expression differs from dorsal root ganglion and is modulated by deep tissue inflammation. Pain, 117 (3), 280-291. 13. Keeble, J., Russell, F., Curtis, B., Starr, A., Pinter, E. and Brain, S.D. (2005), Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation. Arthritis and Rheumatism, 52 (10), 3248-3256. 14. Jongen, J.L.M., Haasdijk, E.D., Sabel-Goedknegt, H., van der Burga, J., Vecht, C.J. and Holstege, J.C. (2005), Intrathecal injection of GDNF and BDNF induces immediate early gene expression in rat spinal dorsal horn. Experimental Neurology, 194 (1), 255-266. 15. Xiang, S.L., Pan, W.H. and Kastin, A.J. (2005), Strategies to create a regenerating environment for the injured spinal cord. Current Pharmaceutical Design, 11 (10), 1267-1277. 16. bd El-Aleem, S.A., Morales-Aza, B.M., McQueen, D.S. and Donaldson, L.F. (2005), Inflammation alters somatostatin mRNA expression in sensory neurons in the rat. European Journal of Neuroscience, 21 (1), 135-141. 17. Tamura, S., Morikawa, Y. and Senba, E. (2005), TRPV2, a capsaicin receptor homologue, is expressed predominantly in the neurotrophin-3-dependent subpopulation of primary sensory neurons. Neuroscience, 130 (1), 223-228. 18. Amaya, F., Shimosato, G., Nagano, M., Ueda, M., Hashimoto, S., Tanaka, Y., Suzuki, H. and Tanaka, M. (2004), NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia. European Journal of Neuroscience, 20 (9), 2303-2310. 19. Caleo, M. and Cenni, M.C. (2004), Anterograde transport of neurotrophic factors - Possible therapeutic implications. Molecular Neurobiology, 29 (2), 179-195. 20. Zwick, M., Molliver, D.C., Lindsay, J., Fairbanks, C.A., Sengoku, T., Albers, K.M. and Davis, B.M. (2003), Transgenic mice possessing increased numbers of nociceptors do not exhibit increased behavioral sensitivity in models of inflammatory and neuropathic pain. Pain, 106 (3), 491-500. 21. Ramer, M.S., Bradbury, E.J., Michael, G.J., Lever, I.J. and McMahon, S.B. (2003), Glial cell line-derived neurotrophic factor increases calcitonin gene-related peptide immunoreactivity in sensory and motoneurons in vivo. European Journal of Neuroscience, 18 (10), 2713-2721.