Induction of high mobility group box-1 in dorsal root ganglion contributes to pain hypersensitivity after peripheral nerve injury.
Pro-inflammatory cytokine high mobility group box-1 (HMGB-1) is involved in inflammation in the central nervous system, but less is known about its biological effects in the peripheral nervous system. In the present study, the role of HMGB-1 in the primary afferent nerve was investigated in the context of the pathophysiology of peripheral nerve injury-induced pain hypersensitivity. Real-time PCR confirmed an increase in HMGB-1 mRNA expression in the dorsal root ganglion (DRG) and spinal nerve at 1 day after spinal nerve ligation (SNL). Induction of HMGB-1 mRNA was observed in both injured L5 and uninjured L4. Immunohistochemistry for HMGB-1 revealed that SNL-induced HMGB-1 expression in the primary afferent neurons and satellite glial cells (SGCs) in the DRG, and in Schwann cells in the spinal nerve. Up-regulation of HMGB-1 was associated with translocation of its signal from the nucleus to the cytoplasm. Injection of HMGB-1 into the sciatic nerve produces transient behavioural hyperalgesia. Neutralizing antibody against HMGB-1 successfully alleviated the mechanical allodynia observed after SNL treatment. Receptor for advanced glycation end products (RAGE), one of the major receptors for HMGB-1, was expressed in the primary afferent neurons and SGCs in the DRG, as well as in Schwann cells in the spinal nerve. These results indicate that HMGB-1 is synthesized and secreted into the DRG and spinal nerve, and contributes to the development of neuropathic pain after nerve injury. Blocking HMGB-1/RAGE signalling might thus be a promising therapeutic strategy for the management of neuropathic pain.
Shibasaki
Masayuki
M
Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Sasaki
Mika
M
Miura
Mayumi
M
Mizukoshi
Keiko
K
Ueno
Hiroshi
H
Hashimoto
Satoru
S
Tanaka
Yoshifumi
Y
Amaya
Fumimasa
F
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D024243:HMGB1 Protein / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000503:physiopathology
D024243:HMGB1 Protein; C104200:Hbp1 protein, rat
Amaya F, Samad TA, Barrett L, Broom DC, Woolf CJ. Periganglionic inflammation elicits a distally radiating pain hypersensitivity by promoting COX-2 induction in the dorsal root ganglion. Pain. 2009;142:59-67.
Amaya F, Shimosato G, Nagano M, Ueda M, Hashimoto S, Tanaka Y, Suzuki H, Tanaka M. NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia. Eur J Neurosci. 2004;20:2303-2310.
Andersson A, Covacu R, Sunnemark D, Danilov AI, Dal Bianco A, Khademi M, Wallstrom E, Lobell A, Brundin L, Lassmann H, Harris RA. Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. J Leukoc Biol. 2008;84:1248-1255.
Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, Janson A, Kokkola R, Zhang M, Yang H, Tracey KJ. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 2000;192:565-570.
Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji RR, Bean BP, Woolf CJ, Samad TA. Nociceptors are interleukin-1β sensors. J Neurosci. 2008;28:14062-14073.
Campana WM. Schwann cells: activated peripheral glia and their role in neuropathic pain. Brain Behav Immun. 2007;21:522-527.
Chacur M, Milligan ED, Gazda LS, Armstrong C, Wang H, Tracey KJ, Maier SF, Watkins LR. A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats. Pain. 2001;94:231-244.
Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature. 2005;438:1017-1021.
Fukuoka T, Tokunaga A, Tachibana T, Dai Y, Yamanaka H, Noguchi K. VR1, but not P2X(3), increases in the spared L4 DRG in rats with L5 spinal nerve ligation. Pain. 2002;99:111-120.
Gardella S, Andrei C, Ferrera D, Lotti LV, Torrisi MR, Bianchi ME, Rubartelli A. The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep. 2002;3:995-1001.
Hanani M, Huang TY, Cherkas PS, Ledda M, Pannese E. Glial cell plasticity in sensory ganglia induced by nerve damage. Neuroscience. 2002;114:279-283.
Harris HE, Raucci A. Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep. 2006;7:774-778.
Ibi M, Matsuno K, Shiba D, Katsuyama M, Iwata K, Kakehi T, Nakagawa T, Sango K, Shirai Y, Yokoyama T, Kaneko S, Saito N, Yabe-Nishimura C. Reactive oxygen species derived from NOX1/NADPH oxidase enhance inflammatory pain. J Neurosci. 2008;28:9486-9494.
Inoue K. The function of microglia through purinergic receptors: neuropathic pain and cytokine release. Pharmacol Ther. 2006;109:210-226.
Joseph EK, Levine JD. Caspase signalling in neuropathic and inflammatory pain in the rat. Eur J Neurosci. 2004;20:2896-2902.
Kalinina N, Agrotis A, Antropova Y, DiVitto G, Kanellakis P, Kostolias G, Ilyinskaya O, Tararak E, Bobik A. Increased expression of the DNA-binding cytokine HMGB1 in human atherosclerotic lesions: role of activated macrophages and cytokines. Arterioscler Thromb Vasc Biol. 2004;24:2320-2325.
Kawasaki Y, Xu ZZ, Wang X, Park JY, Zhuang ZY, Tan PH, Gao YJ, Roy K, Corfas G, Lo EH, Ji RR. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med. 2008;14:331-336.
Kawasaki Y, Zhang L, Cheng JK, Ji RR. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1β, interleukin-6, and tumor necrosis factor-α in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci. 2008;28:5189-5194.
Kim D, Kim MA, Cho IH, Kim MS, Lee S, Jo EK, Choi SY, Park K, Kim JS, Akira S, Na HS, Oh SB, Lee SJ. A critical role of Toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. J Biol Chem. 2007;282:14975-14983.
Kim JB, Lim CM, Yu YM, Lee JK. Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain. J Neurosci Res. 2008;86:1125-1131.
Kim JB, Sig Choi J, Yu YM, Nam K, Piao CS, Kim SW, Lee MH, Han PL, Park JS, Lee JK. HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci. 2006;26:6413-6421.
Kim JY, Park JS, Strassheim D, Douglas I, Diaz del Valle F, Asehnoune K, Mitra S, Kwak SH, Yamada S, Maruyama I, Ishizaka A, Abraham E. HMGB1 contributes to the development of acute lung injury after hemorrhage. Am J Physiol Lung Cell Mol Physiol. 2005;288:L958-965.
Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 1992;50:355-363.
Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A. HMGB1: endogenous danger signaling. Mol Med. 2008;14:476-484.
Kohno T, Anzai T, Naito K, Miyasho T, Okamoto M, Yokota H, Yamada S, Maekawa Y, Takahashi T, Yoshikawa T, Ishizaka A, Ogawa S. Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling. Cardiovasc Res. 2009;81:565-573.
Lin CR, Amaya F, Barrett L, Wang H, Takada J, Samad TA, Woolf CJ. Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity. J Pharmacol Exp Ther. 2006;319:1096-1103.
Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL, Miller RJ. Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci. 2001;21:5027-5035.
Pedrazzi M, Patrone M, Passalacqua M, Ranzato E, Colamassaro D, Sparatore B, Pontremoli S, Melloni E. Selective proinflammatory activation of astrocytes by high-mobility group box 1 protein signaling. J Immunol. 2007;179:8525-8532.
Qiu J, Nishimura M, Wang Y, Sims JR, Qiu S, Savitz SI, Salomone S, Moskowitz MA. Early release of HMGB-1 from neurons after the onset of brain ischemia. J Cereb Blood Flow Metab. 2008;28:927-938.
Rong LL, Trojaborg W, Qu W, Kostov K, Yan SD, Gooch C, Szabolcs M, Hays AP, Schmidt AM. Antagonism of RAGE suppresses peripheral nerve regeneration. FASEB J. 2004;18:1812-1817.
Schafers M, Geis C, Svensson CI, Luo ZD, Sommer C. Selective increase of tumour necrosis factor-α in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Eur J Neurosci. 2003;17:791-804.
Schafers M, Lee DH, Brors D, Yaksh TL, Sorkin LS. Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-α after spinal nerve ligation. J Neurosci. 2003;23:3028-3038.
Schafers M, Sorkin LS, Geis C, Shubayev VI. Spinal nerve ligation induces transient upregulation of tumor necrosis factor receptors 1 and 2 in injured and adjacent uninjured dorsal root ganglia in the rat. Neurosci Lett. 2003;347:179-182.
Suda K, Kitagawa Y, Ozawa S, Saikawa Y, Ueda M, Ebina M, Yamada S, Hashimoto S, Fukata S, Abraham E, Maruyama I, Kitajima M, Ishizaka A. Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis. World J Surg. 2006;30:1755-1762.
Tanga FY, Nutile-McMenemy N, DeLeo JA. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci USA. 2005;102:5856-5861.
Toth C, Rong LL, Yang C, Martinez J, Song F, Ramji N, Brussee V, Liu W, Durand J, Nguyen MD, Schmidt AM, Zochodne DW. Receptor for advanced glycation end products (RAGEs) and experimental diabetic neuropathy. Diabetes. 2008;57:1002-1017.
Triolo D, Dina G, Lorenzetti I, Malaguti M, Morana P, Del Carro U, Comi G, Messing A, Quattrini A, Previtali SC. Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage. J Cell Sci. 2006;119:3981-3993.
Ueno H, Matsuda T, Hashimoto S, Amaya F, Kitamura Y, Tanaka M, Kobayashi A, Maruyama I, Yamada S, Hasegawa N, Soejima J, Koh H, Ishizaka A. Contributions of high mobility group box protein in experimental and clinical acute lung injury. Am J Respir Crit Care Med. 2004;170:1310-1316.
Vincent AM, Perrone L, Sullivan KA, Backus C, Sastry AM, Lastoskie C, Feldman EL. Receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress. Endocrinology. 2007;148:548-558.
Woodham P, Anderson PN, Nadim W, Turmaine M. Satellite cells surrounding axotomised rat dorsal root ganglion cells increase expression of a GFAP-like protein. Neurosci Lett. 1989;98:8-12.
Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16:109-110.