Glial Cell-derived Neurotrophic Factor Attenuates Neuropathic Pain in a Mouse Model of Chronic Constriction Injury: Possible Involvement of E-cadherin/p120ctn Signaling

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2014 Mar 7

PMID 24599758

Citations 9

Authors

Cunjin Wang

Hongjun Wang

Jun Pang

Li Li

Suming Zhang

Ge Song

Na Li

Junping Cao

Licai Zhang

Affiliations

Soon will be listed here.

Abstract

Treating neuropathic pain is a major clinical challenge, and several key molecules associated with nociception have been suggested as potential targets for novel analgesics. Many studies have reported the anti-nociceptive effects of glial cell-derived neurotrophic factor (GDNF), but the underlying mechanism remains largely unknown. The present study was performed to assess the effects of GDNF in a mouse model of chronic constriction injury (CCI)-induced neuropathic pain. We also determined the potential role of E-cadherin/p120 catenin (p120ctn) signaling in these effects. Mice received an intrathecal acute injection of PBS, GDNF, and DECMA-1 (an E-cadherin functional blocking antibody) or a combination of DECMA-1 with GDNF on the testing days. Our results demonstrated that CCI caused a rapid decrease in E-cadherin and membrane-associated p120ctn in the spinal dorsal horn. Together, these data demonstrated that E-cadherin-associated p120ctn was upregulated by GDNF and that this upregulation was inhibited by pre-treatment with DECMA-1. Moreover, DECMA-1 significantly inhibited the effect of GDNF on thermal hyperalgesia. These data suggest that GDNF might have a therapeutic potential for the treatment of CCI-induced neuropathic pain and that the E-cadherin/p120ctn might play a role in GDNF-induced attenuation of thermal hyperalgesia.

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References

Arenas E, TRUPP M, Akerud P, Ibanez C . GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo. Neuron. 1995; 15(6):1465-73. DOI: 10.1016/0896-6273(95)90024-1. View

Woolf C, Mannion R . Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet. 1999; 353(9168):1959-64. DOI: 10.1016/S0140-6736(99)01307-0. View

Boucher T, Okuse K, Bennett D, Munson J, Wood J, McMahon S . Potent analgesic effects of GDNF in neuropathic pain states. Science. 2000; 290(5489):124-7. DOI: 10.1126/science.290.5489.124. View

Shapiro L, Fannon A, Kwong P, Thompson A, Lehmann M, Grubel G . Structural basis of cell-cell adhesion by cadherins. Nature. 1995; 374(6520):327-37. DOI: 10.1038/374327a0. View

Wang R, Guo W, Ossipov M, Vanderah T, Porreca F, Lai J . Glial cell line-derived neurotrophic factor normalizes neurochemical changes in injured dorsal root ganglion neurons and prevents the expression of experimental neuropathic pain. Neuroscience. 2003; 121(3):815-24. DOI: 10.1016/s0306-4522(03)00491-3. View

Poulopoulos A, Aramuni G, Meyer G, Soykan T, Hoon M, Papadopoulos T . Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin. Neuron. 2009; 63(5):628-42. DOI: 10.1016/j.neuron.2009.08.023. View

Brouxhon S, Kyrkanides S, Teng X, Raja V, OBanion M, Clarke R . Monoclonal antibody against the ectodomain of E-cadherin (DECMA-1) suppresses breast carcinogenesis: involvement of the HER/PI3K/Akt/mTOR and IAP pathways. Clin Cancer Res. 2013; 19(12):3234-46. PMC: 4014632. DOI: 10.1158/1078-0432.CCR-12-2747. View

Airaksinen M, Saarma M . The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci. 2002; 3(5):383-94. DOI: 10.1038/nrn812. View

Love S, Plaha P, Patel N, Hotton G, Brooks D, Gill S . Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain. Nat Med. 2005; 11(7):703-4. DOI: 10.1038/nm0705-703. View

10.

Xu P, Rosen K, Hedstrom K, Rey O, Guha S, Hart C . Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in Schwann cells through purinergic signaling and the PKC-PKD pathway. Glia. 2013; 61(7):1029-40. PMC: 4165612. DOI: 10.1002/glia.22491. View

11.

Bennett G, Xie Y . A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988; 33(1):87-107. DOI: 10.1016/0304-3959(88)90209-6. View

12.

Belyantseva I, Lewin G . Stability and plasticity of primary afferent projections following nerve regeneration and central degeneration. Eur J Neurosci. 1999; 11(2):457-68. DOI: 10.1046/j.1460-9568.1999.00458.x. View

13.

Sakai A, Asada M, Seno N, Suzuki H . Involvement of neural cell adhesion molecule signaling in glial cell line-derived neurotrophic factor-induced analgesia in a rat model of neuropathic pain. Pain. 2007; 137(2):378-388. DOI: 10.1016/j.pain.2007.09.020. View

14.

Stan A, Pielarski K, Brigadski T, Wittenmayer N, Fedorchenko O, Gohla A . Essential cooperation of N-cadherin and neuroligin-1 in the transsynaptic control of vesicle accumulation. Proc Natl Acad Sci U S A. 2010; 107(24):11116-21. PMC: 2890764. DOI: 10.1073/pnas.0914233107. View

15.

Brock J, Elste A, Huntley G . Distribution and injury-induced plasticity of cadherins in relationship to identified synaptic circuitry in adult rat spinal cord. J Neurosci. 2004; 24(40):8806-17. PMC: 6729957. DOI: 10.1523/JNEUROSCI.2726-04.2004. View

16.

Dong Z, Ma F, Xie H, Wang Y, Wu G . Down-regulation of GFRalpha-1 expression by antisense oligodeoxynucleotide attenuates electroacupuncture analgesia on heat hyperalgesia in a rat model of neuropathic pain. Brain Res Bull. 2006; 69(1):30-6. DOI: 10.1016/j.brainresbull.2005.08.027. View

17.

Petrova Y, Spano M, Gumbiner B . Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion. Mol Biol Cell. 2012; 23(11):2092-108. PMC: 3364174. DOI: 10.1091/mbc.E11-12-1060. View

18.

Charbel Issa P, Lever I, Michael G, Bradbury E, Malcangio M . Intrathecally delivered glial cell line-derived neurotrophic factor produces electrically evoked release of somatostatin in the dorsal horn of the spinal cord. J Neurochem. 2001; 78(2):221-9. DOI: 10.1046/j.1471-4159.2001.00430.x. View

19.

Haanpaa M, Attal N, Backonja M, Baron R, Bennett M, Bouhassira D . NeuPSIG guidelines on neuropathic pain assessment. Pain. 2010; 152(1):14-27. DOI: 10.1016/j.pain.2010.07.031. View

20.

Pascual A, Hidalgo-Figueroa M, Gomez-Diaz R, Lopez-Barneo J . GDNF and protection of adult central catecholaminergic neurons. J Mol Endocrinol. 2011; 46(3):R83-92. DOI: 10.1530/JME-10-0125. View