Advertisement

Peritoneal Administration of Met-RANTES Attenuates Inflammatory and Nociceptive Responses in a Murine Neuropathic Pain Model

  • Jiin-Tarng Liou
    Affiliations
    Department of Anesthesiology, Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC
    Search for articles by this author
  • Chih-Chieh Mao
    Affiliations
    Department of Anesthesiology, Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC
    Search for articles by this author
  • Daniel Ching-Wah Sum
    Affiliations
    Department of Anesthesiology, Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC
    Search for articles by this author
  • Fu-Chao Liu
    Affiliations
    Department of Anesthesiology, Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC
    Search for articles by this author
  • Ying-Shu Lai
    Affiliations
    Department of Anesthesiology, Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC
    Search for articles by this author
  • Jui-Chin Li
    Affiliations
    Department of Anesthesiology, Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC
    Search for articles by this author
  • Yuan-Ji Day
    Correspondence
    Address reprint requests to Dr. Yuan-Ji Day, PhD, Department of Anesthesiology, Chang Gung Memorial Hospital, No. 5, Fushing Rd, Gueishan Taoyuan, 333 Taiwan, ROC.
    Affiliations
    Department of Anesthesiology, Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC
    Search for articles by this author
Published:November 26, 2012DOI:https://doi.org/10.1016/j.jpain.2012.09.015

      Abstract

      The C-C motif chemokine ligand 5 (CCL5; also known as regulated on activation, normal T expressed and secreted, or RANTES) is a member of the CC family of chemokines that specifically attract and activate leukocytes to sites of inflammation. Although CCL5 has been implicated in the processing of pain, its detailed mechanisms of action are still unknown. In this study, we investigated the potential of the Met-RANTES, a selective CCL5 receptor antagonist, via peritoneal administration to modulate the recruitment of inflammatory cells in injured sites and attenuate nociceptive responses in a neuropathic pain model in mice. Nociceptive sensitization, immune cell infiltration, multiple cytokine secretion, and opioid peptide expression in damaged nerves were studied. Our results indicated that Met-RANTES-treated mice had less behavioral hypersensitivity after partial sciatic nerve ligation. Macrophage infiltration, pro-inflammatory cytokine (TNFα, IL-1β, IL-6, and IFNγ) protein secretion, and enkephalin, β-endorphin, and dynorphin mRNA expression in damaged nerves following partial sciatic nerve ligation were significantly decreased, and anti-inflammatory cytokine (IL-10) protein was significantly increased in Met-RANTES-treated mice. These results suggest that CCL5 is capable of regulating the microenvironment that controls behavioral hypersensitivity at the level of the peripheral injured site in a murine chronic neuropathic pain model.

      Perspective

      The present study identifies the potent pro-inflammatory potential of CCL5 and verifies the possible role of selective CCL5 receptor inhibitor in a murine neuropathic pain model.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ahn D.K.
        • Lee K.R.
        • Lee H.J.
        • Kim S.K.
        • Choi H.S.
        • Lim E.J.
        • Park J.S.
        Intracisternal administration of chemokines facilitated formalin-induced behavioral responses in the orofacial area of freely moving rats.
        Brain Res Bull. 2005; 66: 50-58
        • Ajuebor M.N.
        • Hogaboam C.M.
        • Kunkel S.L.
        • Proudfoot A.E.I.
        • Wallace J.L.
        The Chemokine RANTES Is a Crucial Mediator of the Progression from Acute to Chronic Colitis in the Rat.
        J Immunol. 2001; 166: 552-558
        • Bacon K.B.
        • Harrison J.K.
        Chemokines and their receptors in neurobiology: Perspectives in physiology and homeostasis.
        J Neuroimmunol. 2000; 104: 92-97
        • Bajetto A.
        • Bonavia R.
        • Barbero S.
        • Florio T.
        • Schettini G.
        Chemokines and their receptors in the central nervous system.
        Front Neuroendocrinol. 2001; 22: 147-184
        • Bajetto A.
        • Bonavia R.
        • Barbero S.
        • Schettini G.
        Characterization of chemokines and their receptors in the central nervous system: Physiopathological implications.
        J Neurochem. 2002; 82: 1311-1329
        • Benamar K.
        • Geller E.B.
        • Adler M.W.
        Elevated level of the proinflammatory chemokine, RANTES/CCL5, in the periaqueductal grey causes hyperalgesia in rats.
        Eur J Pharmacol. 2008; 592: 93-95
        • Bless N.M.
        • Huber-Lang M.
        • Guo R.F.
        • Warner R.L.
        • Schmal H.
        • Czermak B.J.
        • Shanley T.P.
        • Crouch L.D.
        • Lentsch A.B.
        • Sarma V.
        • Mulligan M.S.
        • Friedl H.P.
        • Ward P.A.
        Role of CC Chemokines (Macrophage Inflammatory Protein-1{beta}, Monocyte Chemoattractant Protein-1, RANTES) in Acute Lung Injury in Rats.
        J Immunol. 2000; 164: 2650-2659
        • Brack A.
        • Rittner H.L.
        • Machelska H.
        • Beschmann K.
        • Sitte N.
        • Schafer M.
        • Stein C.
        Mobilization of opioid-containing polymorphonuclear cells by hematopoietic growth factors and influence on inflammatory pain.
        Anesthesiology. 2004; 100: 149-157
        • Campbell J.N.
        • Meyer R.A.
        Mechanisms of Neuropathic Pain.
        Neuron. 2006; 52: 77-92
        • Cocchi F.
        • DeVico A.L.
        • Garzino-Demo A.
        • Arya S.K.
        • Gallo R.C.
        • Lusso P.
        Identification of RANTES, MIP-1alpha, and MIP-1beta as the major HIV-suppressive factors produced by CD8 positive T cells.
        Science. 1995; 15: 1811-1815
        • Cunha F.Q.
        • Ferreira S.H.
        Peripheral hyperalgesic cytokines.
        Adv Exp Med Biol. 2003; 521: 22-39
        • Cunha F.Q.
        • Lorenzetti B.B.
        • Poole S.
        • Ferreira S.H.
        Interleukin-8 as a mediator of sympathetic pain.
        Br J Pharmacol. 1991; 104: 765-767
        • Cunha F.Q.
        • Poole S.
        • Lorenzetti B.B.
        • Ferreira S.H.
        The pivotal role of tumour necrosis factor α in the development of inflammatory hyperalgesia.
        Brit J Pharmacol. 1992; 107: 660-664
        • DeLeo J.A.
        • Colburn R.W.
        • Rickman A.J.
        Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy.
        Brain Research. 1997; 759: 50-57
        • Fallon P.G.
        • Jolin H.E.
        • Smith P.
        • Emson C.L.
        • Townsend M.J.
        • Fallon R.
        • Smith P.
        • McKenzie A.N.J.
        IL-4 Induces Characteristic Th2 Responses Even in the Combined Absence of IL-5, IL-9, and IL-13.
        Immunity. 2002; 17: 7-17
        • Ferreira S.H.
        • Lorenzetti B.B.
        • Bristow A.F.
        • Poole S.
        Interleukin-1[beta] as a potent hyperalgesic agent antagonized by a tripeptide analogue.
        Nature. 1988; 334: 698-700
        • Fischer F.R.
        • Luo Y.
        • Luo M.
        • Santambrogio L.
        • Dorf M.E.
        RANTES-Induced Chemokine Cascade in Dendritic Cells.
        J Immunol. 2001; 167: 1637-1643
        • Frisén J.
        • Risling M.
        • Fried K.
        Distribution and axonal relations of macrophages in a neuroma.
        Neuroscience. 1993; 55: 1003-1013
        • Gao Y.J.
        • Ji R.R.
        Chemokines, neuronal-glial interactions, and central processing of neuropathic pain.
        Pharmacol Ther. 2010; 126: 56-68
        • Honda T.
        • Domon H.
        • Okui T.
        • Kajita K.
        • Amanuma R.
        • Yamazaki K.
        Balance of inflammatory response in stable gingivitis and progressive periodontitis lesions.
        Clin Exp Immunol. 2006; 144: 35-40
        • Huang X.R.
        • Kitching A.R.
        • Tipping P.G.
        • Holdsworth S.R.
        Interleukin-10 inhibits macrophage-induced glomerular injury.
        J Am Soc Nephrol. 2000; 11: 262-269
        • Keophiphath M.
        • Rouault C.
        • Divoux A.
        • Clement K.
        • Lacasa D.
        CCL5 Promotes Macrophage Recruitment and Survival in Human Adipose Tissue.
        Arterioscler Thromb Vasc Biol. 2010; 30: 39-45
        • Keswani S.C.
        • Polley M.
        • Pardo C.A.
        • Griffin J.W.
        • McArthur J.C.
        • Hoke A.
        Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons.
        Ann Neurol. 2003; 54: 287-296
        • Kraaijeveld A.O.
        • de Jager S.C.
        • de Jager W.J.
        • Prakken B.J.
        • McColl S.R.
        • Haspels I.
        • Putter H.
        • van Berkel T.J.
        • Nagelkerken L.
        • Jukema J.W.
        • Biessen E.A.
        CC chemokine ligand-5 (CCL5/RANTES) and CC chemokine ligand-18 (CCL18/PARC) are specific markers of refractory unstable angina pectoris and are transiently raised during severe ischemic symptoms.
        Circulation. 2007; 116: 1931-1941
        • Labuz D.
        • Schmidt Y.
        • Schreiter A.
        • Rittner H.L.
        • Mousa S.A.
        • Machelska H.
        Immune cell-derived opioids protect against neuropathic pain in mice.
        J Clin Invest. 2009; 119: 278-286
        • Liou J.T.
        • Liu F.C.
        • Mao C.C.
        • Lai Y.S.
        • Day Y.J.
        Inflammation confers dual effects on nociceptive processing in chronic neuropathic pain model.
        Anesthesiology. 2011; 114: 660-672
        • Liou J.T.
        • Lui P.W.
        • Liu F.C.
        • Lai Y.S.
        • Day Y.J.
        Exogenous granulocyte colony-stimulating factor exacerbate pain-related behaviors after peripheral nerve injury.
        J Neuroimmunol. 2011; 232: 83-93
        • Livak K.J.
        • Schmittgen T.D.
        Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-(Delta Delta C[T]) Method.
        Methods. 2001; 25: 402-408
        • Lloyd C.M.
        • Minto A.W.
        • Dorf M.E.
        • Proudfoot A.
        • Wells T.N.
        • Salant D.J.
        • Gutierrez-Ramos J.C.
        RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis.
        J Exp Med. 1997; 185: 1371-1380
        • Locati M.
        • Deuschle U.
        • Massardi M.L.
        • Martinez F.O.
        • Sironi M.
        • Sozzani S.
        • Bartfai T.
        • Mantovani A.
        Analysis of the Gene Expression Profile Activated by the CC Chemokine Ligand 5/RANTES and by Lipopolysaccharide in Human Monocytes.
        J Immunol. 2002; 168: 3557-3562
        • Lorenzen A.
        • Kennedy S.W.
        A Fluorescence-Based Protein Assay for Use with a Microplate Reader.
        Anal Biochem. 1993; 214: 346-348
        • Lunzer M.M.
        • Yekkirala A.
        • Hebbel R.P.
        • Portoghese P.S.
        Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia.
        Proc Natl Acad Sci U.S.A. 2007; 104: 6061-6065
        • Machelska H.
        • Cabot P.J.
        • Mousa S.A.
        • Zhang Q.
        • Stein C.
        Pain control in inflammation governed by selectins.
        Nat Med. 1998; 4: 1425-1428
        • Machelska H.
        • Mousa S.A.
        • Brack A.
        • Schopohl J.K.
        • Rittner H.L.
        • Schafer M.
        • Stein C.
        Opioid Control of Inflammatory Pain Regulated by Intercellular Adhesion Molecule-1.
        J Neurosci. 2002; 22: 5588-5596
        • Marchesi F.
        • Piemonti L.
        • Mantovani A.
        • Allavena P.
        Molecular mechanisms of perineural invasion, a forgotten pathway of dissemination and metastasis.
        Cytokine Growth Factor Rev. 2010; 21: 77-82
        • Moalem G.
        • Tracey D.J.
        Immune and inflammatory mechanisms in neuropathic pain.
        Brain Res Rev. 2006; 51: 240-264
        • Murdoch J.R.
        • Lloyd C.M.
        Chronic inflammation and asthma.
        Mutat Res. 2010; 690: 24-39
        • Oh S.B.
        • Tran P.B.
        • Gillard S.E.
        • Hurley R.W.
        • Hammond D.L.
        • Miller R.J.
        Chemokines and Glycoprotein120 Produce Pain Hypersensitivity by Directly Exciting Primary Nociceptive Neurons.
        J Neurosci. 2001; 21: 5027-5035
        • Padi S.S.
        • Shi X.Q.
        • Zhao Y.Q.
        • Ruff M.R.
        • Baichoo N.
        • Pert C.B.
        • Zhang J.
        Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks.
        Pain. 2012; 153: 95-106
        • Perkins N.M.
        • Tracey D.J.
        Hyperalgesia due to nerve injury: Role of neutrophils.
        Neuroscience. 2000; 101: 745-757
        • Perry V.H.
        • Brown M.C.
        • Gordon S.
        The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration.
        J Exp Med. 1987; 165: 1218-1223
        • Plater-Zyberk C.
        • Hoogewerf A.J.
        • Proudfoot A.E.I.
        • Power C.A.
        • Wells T.N.C.
        Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice.
        Immunol Lett. 1997; 57: 117-120
        • Repeke C.E.
        • Ferreira Jr., S.B.
        • Vieira A.E.
        • Silveira E.M.
        • Avila-Campos M.J.
        • da Silva J.S.
        • Santos C.F.
        • Campanelli A.P.
        • Trombone A.P.
        • Garlet G.P.
        Dose-response met-RANTES treatment of experimental periodontitis: A narrow edge between the disease severity attenuation and infection control.
        PLoS.One. 2011; 6: e22526
        • Richter G.
        • Kruger-Krasagakes S.
        • Hein G.
        • Huls C.
        • Schmitt E.
        • Diamantstein T.
        • Blankenstein T.
        Interleukin 10 transfected into Chinese hamster ovary cells prevents tumor growth and macrophage infiltration.
        Cancer Res. 1993; 53: 4134-4137
        • Rittner H.L.M.
        • Brack A.M.D.
        • Machelska H.P.
        • Mousa S.A.P.
        • Bauer M.P.
        • Schafer M.M.D.
        • Stein C.M.D.
        Opioid Peptide-expressing Leukocytes: Identification, Recruitment, and Simultaneously Increasing Inhibition of Inflammatory Pain.
        Anesthesiology. 2001; 95: 500-508
        • Savarin-Vuaillat C.
        • Ransohoff R.M.
        Chemokines and chemokine receptors in neurological disease: Raise, retain, or reduce?.
        Neurotherapeutics. 2007; 4: 590-601
        • Skwor T.A.
        • Cho H.
        • Cassidy C.
        • Yoshimura T.
        • McMurray D.N.
        Recombinant guinea pig CCL5 (RANTES) differentially modulates cytokine production in alveolar and peritoneal macrophages.
        J Leukoc Biol. 2004; 76: 1229-1239
        • Stumpf C.
        • Seybold K.
        • Petzi S.
        • Wasmeier G.
        • Raaz D.
        • Yilmaz A.
        • Anger T.
        • Daniel W.G.
        • Garlichs C.D.
        Interleukin-10 improves left ventricular function in rats with heart failure subsequent to myocardial infarction.
        Eur J Heart Fail. 2008; 10: 733-739
        • Thacker M.A.
        • Clark A.K.
        • Bishop T.
        • Grist J.
        • Yip P.K.
        • Moon L.D.F.
        • Thompson S.W.N.
        • Marchand F.
        • McMahon S.B.
        CCL2 is a key mediator of microglia activation in neuropathic pain states.
        Eur J Pain. 2009; 13: 263-272
        • Thacker M.A.
        • Clark A.K.
        • Marchand F.
        • McMahon S.B.
        Pathophysiology of Peripheral Neuropathic Pain: Immune Cells and Molecules.
        Anesth Analg. 2007; 105: 838-847
        • Ubogu E.E.
        Chemokine receptors as specific anti-inflammatory targets in peripheral nerves.
        Endocr Metab Immune Disord Drug Targets. 2011; 11: 141-153
        • Ubogu E.E.
        • Callahan M.K.
        • Tucky B.H.
        • Ransohoff R.M.
        CCR5 expression on monocytes and T cells: modulation by transmigration across the blood-brain barrier in vitro.
        Cell Immunol. 2006; 243: 19-29
        • Udenfriend S.
        • Stein S.
        • Bohlen P.
        • Dairman W.
        • Leimgruber W.
        • Weigele M.
        Fluorescamine: A reagent for assay of amino acids, peptides, proteins, and primary amines in the picomole range.
        Science. 1972; 178: 871-872
        • Watkins L.R.
        • Maier S.F.
        Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States.
        Physiol Rev. 2002; 82: 981-1011
        • Watkins L.R.
        • Wiertelak E.P.
        • Goehler L.E.
        • Smith K.P.
        • Martin D.
        • Maier S.F.
        Characterization of cytokine-induced hyperalgesia.
        Brain Research. 1994; 654: 15-26
        • Wesselingh S.L.
        • Thompson K.A.
        Immunopathogenesis of HIV-associated dementia.
        Curr Opin Neurol. 2001; 14: 375-379
        • White F.A.
        • Miller R.J.
        Insights into the regulation of chemokine receptors by molecular signaling pathways: Functional roles in neuropathic pain.
        Brain Behav.Immun. 2010; 24: 859-865
        • White F.A.
        • Jung H.
        • Miller R.J.
        Chemokines and the pathophysiology of neuropathic pain.
        Proc Natl Acad Sci U S A. 2007; 104: 20151-20158
        • Wu H.
        • Ghosh S.
        • Perrard X.D.
        • Feng L.
        • Garcia G.E.
        • Perrard J.L.
        • Sweeney J.F.
        • Peterson L.E.
        • Chan L.
        • Smith C.W.
        • Ballantyne C.M.
        T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity.
        Circulation. 2007; 115: 1029-1038