Somatostatin Type 2 Receptor Antibody Enhances Mechanical Hyperalgesia in the Dorsal Root Ganglion Neurons after Sciatic Nerve-pinch Injury: Evidence of Behavioral Studies and Bax Protein Expression

Author(s): Qiong Xiang, Jing-Jing Li, Chun-Yan Li, Rong-Bo Tian, Xian-Hui Li*

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 18 , Issue 10 , 2019


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Our previous study has indicated that somatostatin potently inhibits neuropathic pain through the activation of its type 2 receptor (SSTR2) in mouse dorsal root ganglion and spinal cord. However, the underlying mechanism of this activation has not been elucidated clearly.

Objective: The aim of this study is to perform the pharmacological studies on the basis of sciatic nerve-pinch mice model and explore the underlying mechanism involving SSTR2.

Methods: On the basis of a sciatic nerve-pinch injury model, we aimed at comparing the painful behavior and dorsal root ganglion neurons neurochemical changes after the SSTR2 antibody (anti- SSTR2;5μl,1μg/ml) administration in the mouse.

Results: After pinch nerve injury, we found that the mechanical hyperalgesia and severely painful behavior (autotomy) were detected after the application of SSTR2 antibody (anti-SSTR2; 5μl, 1μg/ml) on the pinch-injured nerve. The up-regulated phosphorylated ERK (p-ERK) expression and the apoptotic marker (i.e., Bax) were significantly decreased in DRGs after anti-SSTR2 treatment.

Conclusion: The current data suggested that inhibitory changes in proteins from the apoptotic pathway in anti-SSTR2-treated groups might be taking place to overcome the protein deficits caused by SSTR2 antibody and supported the new therapeutic intervention with SSTR2 antagonist for neuronal degeneration following nerve injury.

Keywords: Somatostatin, somatostatin type-2 receptor, DRG, Bax protein, pinch nerve injury, painful behavior.

[1]
Kimura N, Schindler M, Kasai N, Kimura I. Immunohistochemical localization of somatostatin receptor type 2A in rat and human tissues. Endocr J 2001; 48(1): 95-102.
[http://dx.doi.org/10.1507/endocrj.48.95] [PMID: 11403108]
[2]
De Martino MC, Hofland LJ, Lamberts SW. Somatostatin and somatostatin receptors: From basic concepts to clinical applications. Prog Brain Res In: 2010; 182: pp. 255-80.
[http://dx.doi.org/10.1016/S0079-6123(10)82011-4] [PMID: 20541669]
[3]
Olias G, Viollet C, Kusserow H, Epelbaum J, Meyerhof W. Regulation and function of somatostatin receptors. J Neurochem 2004; 89(5): 1057-91.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02402.x] [PMID: 15147500]
[4]
Reubi JC. Regulatory peptide receptors as molecular targets for cancer diagnosis and therapy. Q J Nucl Med 1997; 41(2): 63-70.
[PMID: 9203845]
[5]
Song P, Hu JY, Zhao ZQ. Spinal somatostatin SSTR2A receptors are preferentially up-regulated and involved in thermonociception but not mechanonociception. Exp Neurol 2002; 178(2): 280-7.
[http://dx.doi.org/10.1006/exnr.2002.8025] [PMID: 12504886]
[6]
Zhao J, Hu JY, Zhang YQ, Zhao ZQ. Involvement of spinal somatostatin receptor SST(2A) in inflammation-induced thermal hyperalgesia: Ultrastructural and behavioral studies in rats. Neurochem Res 2008; 33(10): 2099-106.
[http://dx.doi.org/10.1007/s11064-008-9713-x] [PMID: 18452056]
[7]
Epelbaum J, Dournaud P, Fodor M, Viollet C. The neurobiology of somatostatin. Crit Rev Neurobiol 1994; 8(1-2): 25-44.
[PMID: 7907281]
[8]
Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol 1999; 20(3): 157-98.
[http://dx.doi.org/10.1006/frne.1999.0183] [PMID: 10433861]
[9]
Dupré DJ, Hébert TE. Biosynthesis and trafficking of seven transmembrane receptor signalling complexes. Cell Signal 2006; 18(10): 1549-59.
[http://dx.doi.org/10.1016/j.cellsig.2006.03.009] [PMID: 16677801]
[10]
Presky DH, Schonbrunn A. Iodination of [Tyr11]somatostatin yields a super high affinity ligand for somatostatin receptors in GH4C1 pituitary cells. Mol Pharmacol 1988; 34(5): 651-8.
[PMID: 2904115]
[11]
Schottelius M, Poethko T, Herz M, et al. First (18)F-labeled tracer suitable for routine clinical imaging of sst receptor-expressing tumors using positron emission tomography. Clin Cancer Res 2004; 10(11): 3593-606.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0359] [PMID: 15173065]
[12]
Wild D, Schmitt JS, Ginj M, et al. DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals. Eur J Nucl Med Mol Imaging 2003; 30(10): 1338-47.
[http://dx.doi.org/10.1007/s00259-003-1255-5] [PMID: 12937948]
[13]
Nock B, Nikolopoulou A, Chiotellis E, et al. [99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging. Eur J Nucl Med Mol Imaging 2003; 30(2): 247-58.
[http://dx.doi.org/10.1007/s00259-002-1040-x] [PMID: 12552343]
[14]
Wang M, Caruano AL, Lewis MR, Meyer LA, VanderWaal RP, Anderson CJ. Subcellular localization of radiolabeled somatostatin analogues: Implications for targeted radiotherapy of cancer. Cancer Res 2003; 63(20): 6864-9.
[PMID: 14583484]
[15]
De Jong M, Bernard BF, De Bruin E, et al. Internalization of radiolabelled [DTPA0]octreotide and [DOTA0,Tyr3]octreotide: Peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy. Nucl Med Commun 1998; 19(3): 283-8.
[http://dx.doi.org/10.1097/00006231-199803000-00013] [PMID: 9625504]
[16]
Liu Q, Cescato R, Dewi DA, Rivier J, Reubi JC, Schonbrunn A. Receptor signaling and endocytosis are differentially regulated by somatostatin analogs. Mol Pharmacol 2005; 68(1): 90-101.
[http://dx.doi.org/10.1124/mol.105.011767] [PMID: 15855408]
[17]
Shi TJ, Xiang Q, Zhang MD, et al. Somatostatin and its 2A receptor in dorsal root ganglia and dorsal horn of mouse and human: Expression, trafficking and possible role in pain. Mol Pain 2014; 10: 12.
[http://dx.doi.org/10.1186/1744-8069-10-12] [PMID: 24521084]
[18]
Miki K, Fukuoka T, Tokunaga A, Noguchi K. Calcitonin gene-related peptide increase in the rat spinal dorsal horn and dorsal column nucleus following peripheral nerve injury: up-regulation in a subpopulation of primary afferent sensory neurons. Neuroscience 1998; 82(4): 1243-52.
[http://dx.doi.org/10.1016/S0306-4522(97)00258-3] [PMID: 9466443]
[19]
Hou C, Kirchner T, Singer M, Matheis M, Argentieri D, Cavender D. In vivo activity of a phospholipase C inhibitor, 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), in acute and chronic inflammatory reactions. J Pharmacol Exp Ther 2004; 309(2): 697-704.
[http://dx.doi.org/10.1124/jpet.103.060574] [PMID: 14730005]
[20]
Engelstoft MS, Park WM, Sakata I, et al. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol Metab 2013; 2(4): 376-92.
[http://dx.doi.org/10.1016/j.molmet.2013.08.006] [PMID: 24327954]
[21]
Patel YC, Greenwood MT, Panetta R, Demchyshyn L, Niznik H, Srikant CB. The somatostatin receptor family. Life Sci 1995; 57(13): 1249-65.
[http://dx.doi.org/10.1016/0024-3205(95)02082-T] [PMID: 7674817]
[22]
Schally AV. Oncological applications of somatostatin analogues. Cancer Res 1988; 48(24 Pt 1): 6977-85.
[PMID: 2903792]
[23]
Mihara S, North RA, Surprenant A. Somatostatin increases an inwardly rectifying potassium conductance in guinea-pig submucous plexus neurons. J Physiol 1987; 390: 335-55.
[http://dx.doi.org/10.1113/jphysiol.1987.sp016704] [PMID: 2450994]
[24]
Moore SD, Madamba SG, Joëls M, Siggins GR. Somatostatin augments the M-current in hippocampal neurons. Science 1988; 239(4837): 278-80.
[http://dx.doi.org/10.1126/science.2892268] [PMID: 2892268]
[25]
Wang HL, Bogen C, Reisine T, Dichter M. Somatostatin-14 and somatostatin-28 induce opposite effects on potassium currents in rat neocortical neurons. Proc Natl Acad Sci USA 1989; 86(23): 9616-20.
[http://dx.doi.org/10.1073/pnas.86.23.9616] [PMID: 2574465]
[26]
Barber DL, McGuire ME, Ganz MB. Beta-adrenergic and somatostatin receptors regulate Na-H exchange independent of cAMP. J Biol Chem 1989; 264(35): 21038-42.
[PMID: 2574175]
[27]
Buscail L, Delesque N, Estève JP, et al. Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: Mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. Proc Natl Acad Sci USA 1994; 91(6): 2315-9.
[http://dx.doi.org/10.1073/pnas.91.6.2315] [PMID: 7907795]
[28]
Cescato R, Loesch KA, Waser B, et al. Agonist-biased signaling at the sst2A receptor: The multi-somatostatin analogs KE108 and SOM230 activate and antagonize distinct signaling pathways. Mol Endocrinol 2010; 24(1): 240-9.
[http://dx.doi.org/10.1210/me.2009-0321] [PMID: 19910453]
[29]
Naveilhan P, Hassani H, Lucas G, et al. Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. Nature 2001; 409(6819): 513-7.
[http://dx.doi.org/10.1038/35054063] [PMID: 11206547]
[30]
Hama A, Natsume T, Ogawa SY, et al. Pain-related behavior and brain activation in a cynomolgus macaque model of postoperative pain. CNS Neurol Disord Drug Targets 2018; 17(5): 348-60.
[http://dx.doi.org/10.2174/1871527317666180515121350]
[31]
Evangelista M. Cilli, De Vitis R, Militerno A, Fanfani F. Ultra-micronized palmitoylethanolamide effects on sleep-wake rhythm and neuropathic pain phenotypes in patients with carpal tunnel syndrome: An open-label, randomized controlled study. CNS Neurol Disord Drug Targets 2018; 17(4): 291-8.
[http://dx.doi.org/10.2174/1871527317666180420143830] [PMID: 29676237]
[32]
Zhang Y, Lian J, Wang X. Actein inhibits cell proliferation and migration and promotes cell apoptosis in human non-small cell lung cancer cells. Oncol Lett 2018; 15(3): 3155-60.
[PMID: 29435050]
[33]
Kang Q, Zou H, Yang X, et al. Characterization and prognostic significance of mortalin, Bcl-2 and Bax in intrahepatic cholangiocarcinoma. Oncol Lett 2018; 15(2): 2161-8.
[PMID: 29434920]
[34]
Wang Y, Gao H, Wu T, et al. Pseudolaric acid B induced autophagy, but not apoptosis, in MRC5 human fibroblast cells. Oncol Lett 2018; 15(1): 863-70.
[PMID: 29399151]
[35]
Maji S, Panda S, Samal SK, et al. Bcl-2 antiapoptotic family proteins and chemoresistance in cancer. Adv Cancer Res 2018; 137: 37-75.
[http://dx.doi.org/10.1016/bs.acr.2017.11.001] [PMID: 29405977]
[36]
Polčic P, Mentel M, Gavurníková G, Bhatia-Kiššová I. To keep the host alive - the role of viral Bcl-2 proteins. Acta Virol 2017; 61(3): 240-51.
[http://dx.doi.org/10.4149/av_2017_302] [PMID: 28854788]
[37]
Lindqvist LM, Vaux DL. BCL2 and related prosurvival proteins require BAK1 and BAX to affect autophagy. Autophagy 2014; 10(8): 1474-5.
[http://dx.doi.org/10.4161/auto.29639] [PMID: 24991825]
[38]
Liu L, Jin X, Hu CF, Li R, Zhou Z, Shen CX. Exosomes derived from mesenchymal stem cells rescue myocardial ischaemia/reperfusion injury by inducing cardiomyocyte autophagy via AMPK and Akt pathways. Cell Physiol Biochem 2017; 43(1): 52-68.
[http://dx.doi.org/10.1159/000480317] [PMID: 28848091]
[39]
Lu Z, Miao Y, Muhammad I, et al. JNK mediated colistin-induced autophagy and apoptosis via JNK-Bcl2-Bax signaling pathway and JNK-p53-ROS positive feedback loop in PC 12 cells. Chem Biol Interact 2017; 277: 62-73.
[http://dx.doi.org/10.1016/j.cbi.2017.08.011] [PMID: 28842171]
[40]
Paizs M, Patai R, Engelhardt JI, Katarova Z, Obal I, Siklos L. Axotomy leads to reduced calcium increase and earlier termination of CCL2 release in spinal motoneurons with upregulated parvalbumin followed by decreased neighboring microglial activation. CNS Neurol Disord Drug Targets 2017; 16(3): 356-67.
[http://dx.doi.org/10.2174/1871527315666161223130409] [PMID: 28017131]
[41]
Wei X, Yang D, Shi T, et al. Metabotropic glutamate receptor 7 (mGluR7) as a target for modulating pain-evoked activities of neurons in the hippocampal CA3 region of rats. CNS Neurol Disord Drug Targets 2017; 16(5): 610-6.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 18
ISSUE: 10
Year: 2019
Published on: 17 January, 2020
Page: [791 - 797]
Pages: 7
DOI: 10.2174/1871527318666191101094412
Price: $65

Article Metrics

PDF: 24
HTML: 7
EPUB: 1
PRC: 2