Skip to main content

Advertisement

SpringerLink
Log in

Dual Peripheral Actions of Immune Cells in Neuropathic Pain

  • REVIEW
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Ability to perceive physiological pain is essential in protecting the individual from tissue destruction. In contrast, pathological chronic pain is an expression of maladaptive alterations outlasting its biological usefulness. In such conditions even eating, speaking or wearing clothes might be painful, as in neuropathic pain. Such pain is caused by diseases or injuries affecting nerves (e.g. diabetes, trigeminal neuralgia or amputation). Neuropathic pain is not an exclusive neuronal phenomenon but also involves immune responses. Damaged peripheral nerves are infiltrated by mast cells, granulocytes, macrophages and T lymphocytes. It is widely emphasized that these cells, via secretion of inflammatory mediators (e.g. proinflammatory cytokines, chemokines), contribute to the generation of neuropathic pain. However, leukocytes are also a source of analgesic mediators such as anti-inflammatory cytokines and opioid peptides. Recent findings indicate that immune cell-derived opioid peptides can interact with opioid receptors in the injured nerves and ameliorate neuropathic pain. Targeting opioid-containing immune cells might represent a new disease-modifying approach based on the use of beneficial effects of neuro-inflammation in painful neuropathies. This review analyzes both detrimental and advantageous actions of leukocytes at peripheral nerves in neuropathic pain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CCI:

Chronic constriction injury

CFA:

Complete Freund’s adjuvant

CGRP:

Calcitonin gene-related peptide

CNS:

Central nervous system

CRF:

Corticotropin-releasing factor

CXCL1:

Chemokine (C-X-C motif) ligand 1 (keratinocyte-derived chemokine)

CXCL2/3:

Chemokine (C-X-C motif) ligand 2 (macrophage inflammatory protein-2)

CXCR2:

CXC chemokine receptor 2

DRG:

Dorsal root ganglion

ICAM-1:

Intercellular adhesion molecule-1

IL:

Interleukin

KO:

Knock-out

PSL:

Partial sciatic nerve ligation

RAG-1:

Recombination-activating gene-1

SCID:

Severe combined immunodeficiency

SNL:

Spinal nerve ligation

TNF-α:

Tumor necrosis factor-α

TRP:

Transient receptor potential ion channels

WT:

Wild type

References

  • Akins PT, McCleskey EW (1993) Characterization of potassium currents in adult rat sensory neurons and modulation by opioids and cyclic AMP. Neuroscience 56:759–769

    CAS  PubMed  Google Scholar 

  • Barclay J, Clark AK, Ganju P et al (2007) Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain 130:225–234

    CAS  PubMed  Google Scholar 

  • Baron R (2006) Mechanisms of disease: neuropathic pain—a clinical perspective. Nat Clin Pract Neurol 2:95–106

    PubMed  Google Scholar 

  • Baron R, Schwarz K, Kleinert A et al (2001) Histamine-induced itch converts into pain in neuropathic hyperalgesia. Neuroreport 12:3475–3478

    CAS  PubMed  Google Scholar 

  • Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:87–107

    CAS  PubMed  Google Scholar 

  • Benoliel R, Epstein J, Eliav E et al (2007) Orofacial pain in cancer. Part I. Mechanisms. J Dent Res 86:491–505

    CAS  PubMed  Google Scholar 

  • Binder W, Mousa SA, Sitte N et al (2004) Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue. Eur J Neurosci 20:92–100

    PubMed  Google Scholar 

  • Börzsei R, Pozsgai G, Bagoly T et al (2008) Inhibitory action of endomorphin-1 on sensory neuropeptide release and neurogenic inflammation in rats and mice. Neuroscience 152:82–88

    PubMed  Google Scholar 

  • Brack A, Labuz D, Schiltz A et al (2004a) Tissue monocytes/macrophages in inflammation: hyperalgesia versus opioid-mediated peripheral antinociception. Anesthesiology 101:204–211

    CAS  PubMed  Google Scholar 

  • Brack A, Rittner HL, Machelska H et al (2004b) Control of inflammatory pain by chemokine-mediated recruitment of opioid-containing polymorphonuclear cells. Pain 112:229–238

    CAS  PubMed  Google Scholar 

  • Bradbury J (2003) Beyond pills and jabs. Researchers develop new ways to get drugs to the right place at the right time. Lancet 362:1984–1985

    PubMed  Google Scholar 

  • Busch-Dienstfertig M, Stein C (2010) Opioid receptors and opioid peptide-producing leukocytes in inflammatory pain: basic and therapeutic aspects. Brain Behav Immun 24:683–694

    CAS  PubMed  Google Scholar 

  • Cabot PJ, Carter L, Gaiddon C et al (1997) Immune cell-derived β-endorphin: production, release and control of inflammatory pain in rats. J Clin Invest 100:142–148

    CAS  PubMed  Google Scholar 

  • Cabot PJ, Carter L, Schäfer M et al (2001) Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain. Pain 93:207–212

    CAS  PubMed  Google Scholar 

  • Campbell JN, Meyer RA (2006) Mechanisms of neuropathic pain. Neuron 52:77–92

    CAS  PubMed  Google Scholar 

  • Cao L, DeLeo JA (2008) CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain. Eur J Immunol 38:448–458

    CAS  PubMed  Google Scholar 

  • Childs EA, Lyles RH, Selnes OA et al (1999) Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy. Neurology 52:607–613

    CAS  PubMed  Google Scholar 

  • Chizhmakov I, Yudin Y, Mamenko N et al (2005) Opioids inhibit purinergic nociceptors in the sensory neurons and fibres of rat via a G protein-dependent mechanism. Neuropharmacology 48:639–647

    CAS  PubMed  Google Scholar 

  • Clatworthy AL, Illich PA, Castro GA et al (1995) Role of peri-axonal inflammation in the development of thermal hyperalgesia and guarding behavior in a rat model of neuropathic pain. Neurosci Lett 184:5–8

    CAS  PubMed  Google Scholar 

  • Costigan M, Moss A, Latremoliere A et al (2009a) T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J Neurosci 29:14415–14422

    CAS  PubMed  Google Scholar 

  • Costigan M, Scholz J, Woolf CJ (2009b) Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 32:1–32

    CAS  PubMed  Google Scholar 

  • Cox JJ, Reimann F, Nicholas AK et al (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444:894–898

    CAS  PubMed  Google Scholar 

  • Cui JG, Holmin S, Mathiesen T et al (2000) Possible role of inflammatory mediators in tactile hypersensivity in rat models of mononeuropathy. Pain 88:239–248

    CAS  PubMed  Google Scholar 

  • Dowdall T, Robinson I, Meert TF (2005) Comparison of five different rat models of peripheral nerve injury. Pharmacol Biochem Behav 80:93–108

    PubMed  Google Scholar 

  • Endres-Becker J, Heppenstall PA, Mousa SA et al (2007) Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain. Mol Pharmacol 71:12–18

    CAS  PubMed  Google Scholar 

  • Fields H (2004) State-dependent opioid control of pain. Nat Rev Neurosci 5:565–575

    CAS  PubMed  Google Scholar 

  • Flatters SJ, Fox AJ, Dickenson AH (2003) Spinal interleukin-6 (IL-6) inhibits nociceptive transmission following neuropathy. Brain Res 984:54–62

    CAS  PubMed  Google Scholar 

  • Flatters SJ, Fox AJ, Dickenson AH (2004) Nerve injury alters the effects of interleukin-6 on nociceptive transmission in peripheral afferents. Eur J Pharmacol 484:183–191

    CAS  PubMed  Google Scholar 

  • Fromont A, De Seze J, Fleury MC et al (2009) Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. Cytokine 45:55–57

    CAS  PubMed  Google Scholar 

  • George A, Marziniak M, Schäfers M et al (2000) Thalidomide treatment in chronic constrictive neuropathy decreases endoneurial tumor necrosis factor-alpha, increases interleukin-10 and has long-term effects on spinal cord dorsal horn met-enkephalin. Pain 88:267–275

    CAS  PubMed  Google Scholar 

  • Gold MS, Levine JD (1996) DAMGO inhibits prostaglandin E2-induced potentiation of a TTX-resistant Na+ current in rat sensory neurons in vitro. Neurosci Lett 212:83–86

    CAS  PubMed  Google Scholar 

  • Grothe C, Heese K, Meisinger C et al (2000) Expression of interleukin-6 and its receptor in the sciatic nerve and cultured Schwann cells: relation to 18-kD fibroblast growth factor-2. Brain Res 885:172–181

    CAS  PubMed  Google Scholar 

  • Herbert MK, Just H, Schmidt RF (2001) Histamine excites groups III and IV afferents from the cat knee joint depending on their resting activity. Neurosci Lett 305:95–98

    CAS  PubMed  Google Scholar 

  • Heumann R, Lindholm D, Bandtlow C et al (1987) Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. Proc Natl Acad Sci USA 84:8735–8739

    CAS  PubMed  Google Scholar 

  • Honore P, Wade CL, Zhong C et al (2006) Interleukin-1alpha/beta gene-deficient mice show reduced nociceptive sensitivity in models of inflammatory and neuropathic pain but not post-operative pain. Behav Brain Res 167:355–364

    CAS  PubMed  Google Scholar 

  • Hsieh GC, Chandran P, Salyers AK et al (2010) H4 receptor antagonism exhibits anti-nociceptive effects in inflammatory and neuropathic pain models in rats. Pharmacol Biochem Behav 95:41–50

    CAS  PubMed  Google Scholar 

  • Hua XY, Chen P, Fox A et al (1996) Involvement of cytokines in lipopolysaccharide-induced facilitation of CGRP release from capsaicin-sensitive nerves in the trachea: studies with interleukin-1beta and tumor necrosis factor-alpha. J Neurosci 16:4742–4748

    CAS  PubMed  Google Scholar 

  • Hua S, Hermanussen S, Tang L et al (2006) The neural cell adhesion molecule antibody blocks cold water swim stress-induced analgesia and cell adhesion between lymphocytes and cultured dorsal root ganglion neurons. Anesth Analg 103:1558–1564

    CAS  PubMed  Google Scholar 

  • Ingram SL, Williams TJ (1994) Opioid inhibition of Ih via adenylyl cyclise. Neuron 13:179–186

    CAS  PubMed  Google Scholar 

  • Kabli N, Cahill CM (2007) Anti-allodynic effects of peripheral delta opioid receptors in neuropathic pain. Pain 127:84–93

    CAS  PubMed  Google Scholar 

  • Kashiba H, Fukui H, Morikawa Y et al (1999) Gene expression of histamine H1 receptor in guinea pig primary sensory neurons: a relationship between H1 receptor mRNA-expressing neurons and peptidergic neurons. Brain Res Mol Brain Res 66:24–34

    CAS  PubMed  Google Scholar 

  • Kerschensteiner M, Gallmeier E, Behrens L et al (1999) Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 189:865–870

    CAS  PubMed  Google Scholar 

  • Kiefer R, Kieseier BC, Stoll G et al (2001) The role of macrophages in immune-mediated damage to the peripheral nervous system. Prog Neurobiol 64:109–127

    CAS  PubMed  Google Scholar 

  • Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50:355–363

    CAS  PubMed  Google Scholar 

  • Kim KJ, Yoon YW, Chung JM (1997) Comparison of three rodent neuropathic pain models. Exp Brain Res 113:200–206

    CAS  PubMed  Google Scholar 

  • Kirsch M, Campos Friz M, Vougioukas VI et al (2009) Wallerian degeneration and axonal regeneration after sciatic nerve crush are altered in ICAM-1-deficient mice. Cell Tissue Res 338:19–28

    CAS  PubMed  Google Scholar 

  • Kleinschnitz C, Hofstetter HH, Meuth SG et al (2006) T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression. Exp Neurol 200:480–485

    CAS  PubMed  Google Scholar 

  • Kohno T, Ji RR, Ito N et al (2005) Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord. Pain 117:77–87

    CAS  PubMed  Google Scholar 

  • Kolesnikov Y, El-Maarouf A, Rutishauser U et al (2007) Reorganization of dorsal root ganglion neurons following chronic sciatic nerve constriction injury: correlation with morphine and lidocaine analgesia. Eur J Pharmacol 568:124–133

    CAS  PubMed  Google Scholar 

  • La Rana G, Russo R, D’Agostino G et al (2008) AM404, an anandamide transport inhibitor, reduces plasma extravasation in a model of neuropathic pain in rat: role for cannabinoid receptors. Neuropharmacology 54:521–529

    CAS  PubMed  Google Scholar 

  • Labuz D, Berger S, Mousa SA et al (2006) Peripheral antinociceptive effects of exogenous and immune cell-derived endomorphins in prolonged inflammatory pain. J Neurosci 6:4350–4358

    Google Scholar 

  • Labuz D, Schmidt Y, Schreiter A et al (2009) Immune cell-derived opioids protect against neuropathic pain in mice. J Clin Invest 119:278–286

    CAS  PubMed  Google Scholar 

  • Labuz D, Schreiter A, Schmidt Y et al (2010) T lymphocytes containing beta-endorphin ameliorate mechanical hypersensitivity following nerve injury. Brain Behav Immun 24:1045–1053

    CAS  PubMed  Google Scholar 

  • Leonard G, Goffaux P, Mathieu D et al (2009) Evidence of descending inhibition deficits in atypical but not classical trigeminal neuralgia. Pain 147:217–223

    PubMed  Google Scholar 

  • Li JL, Ding YQ, Li YQ et al (1998) Immunocytochemical localization of mu-opioid receptor in primary afferent neurons containing substance P or calcitonin gene-related peptide. A light and electron microscope study in the rat. Brain Res 794:347–352

    CAS  PubMed  Google Scholar 

  • Likar R, Mousa SA, Steinkellner H et al (2007) Involvement of intra-articular corticotropin-releasing hormone in postoperative pain modulation. Clin J Pain 23:136–142

    PubMed  Google Scholar 

  • Lindenlaub T, Teuteberg P, Hartung T et al (2000) Effects of neutralizing antibodies to TNF-alpha on pain-related behavior and nerve regeneration in mice with chronic constriction injury. Brain Res 866:15–22

    CAS  PubMed  Google Scholar 

  • Liu T, van Rooijen N, Tracey DJ (2000) Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Pain 86:25–32

    CAS  PubMed  Google Scholar 

  • Ma W, Quirion R (2005) Up-regulation of interleukin-6 induced by prostaglandin E from invading macrophages following nerve injury: an in vivo and in vitro study. J Neurochem 93:664–673

    CAS  PubMed  Google Scholar 

  • Machelska H (2007) Targeting of opioid-producing leukocytes for pain control. Neuropeptides 41:285–293

    Google Scholar 

  • Machelska H, Cabot PJ, Mousa SA et al (1998) Pain control in inflammation governed by selectins. Nat Med 4:1425–1428

    CAS  PubMed  Google Scholar 

  • Machelska H, Mousa SA, Brack A et al (2002) Opioid control of inflammatory pain regulated by intercellular adhesion molecule-1. J Neurosci 22:5588–5596

    CAS  PubMed  Google Scholar 

  • Machelska H, Schopohl JK, Mousa SA et al (2003) Different mechanisms of intrinsic pain inhibition in early and late inflammation. J Neuroimmunol 141:30–39

    CAS  PubMed  Google Scholar 

  • Machelska H, Brack A, Mousa SA et al (2004) Selectins and integrins but not platelet-endothelial cell adhesion molecule-1 regulate opioid inhibition of inflammatory pain. Br J Pharmacol 142:772–780

    CAS  PubMed  Google Scholar 

  • Metcalfe DD (2008) Mast cells and mastocytosis. Blood 112:946–956

    CAS  PubMed  Google Scholar 

  • Miller RJ, Jung H, Bhangoo SK et al (2009) Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol 194:417–449

    CAS  PubMed  Google Scholar 

  • Milligan ED, Sloane EM, Langer SJ et al (2006) Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Pain 126:294–308

    CAS  PubMed  Google Scholar 

  • Minami M, Maekawa K, Yabuuchi K et al (1995) Double in situ hybridization study on coexistence of mu-, delta- and kappa-opioid receptor mRNAs with preprotachykinin A mRNA in the rat dorsal root ganglia. Brain Res Mol Brain Res 30:203–210

    CAS  PubMed  Google Scholar 

  • Mizumura K, Koda H, Kumazawa T (2000) Possible contribution of protein kinase C in the effects of histamine on the visceral nociceptor activities in vitro. Neurosci Res 37:183–190

    CAS  PubMed  Google Scholar 

  • Moalem G, Tracey DL (2006) Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev 51:240–264

    CAS  PubMed  Google Scholar 

  • Moalem G, Xu K, Yu L (2004) T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats. Neuroscience 129:767–777

    CAS  PubMed  Google Scholar 

  • Mousa SA, Zhang Q, Sitte N et al (2001) Beta-Endorphin-containing memory-cells and mu-opioid receptors undergo transport to peripheral inflamed tissue. J Neuroimmunol 115:71–78

    CAS  PubMed  Google Scholar 

  • Mousa SA, Shakibaei M, Sitte N et al (2004) Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain. Endocrinology 145:1331–1341

    CAS  PubMed  Google Scholar 

  • Mousa SA, Straub RH, Schäfer M et al (2007) Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis. Ann Rheum Dis 66:871–879

    CAS  PubMed  Google Scholar 

  • Murphy PG, Ramer MS, Borthwick L et al (1999) Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice. Eur J Neurosci 11:2243–2253

    CAS  PubMed  Google Scholar 

  • Nilsen KB, Nicholas AK, Woods CG et al (2009) Two novel SCN9A mutations causing insensitivity to pain. Pain 143:155–158

    CAS  PubMed  Google Scholar 

  • Nyland H, Matre R, Mørk S (1981) Immunological characterization of sural nerve biopsies from patients with Guillain–Barré syndrome. Ann Neurol 9(suppl):80–86

    PubMed  Google Scholar 

  • Perkins NM, Tracey DJ (2000) Hyperalgesia due to nerve injury: role of neutrophils. Neuroscience 101:745–757

    CAS  PubMed  Google Scholar 

  • Przewlocki R, Przewlocka B (2005) Opioids in neuropathic pain. Curr Pharm Des 11:3013–3025

    CAS  PubMed  Google Scholar 

  • Ramer MS, French GD, Bisby MA (1997) Wallerian degeneration is required for both neuropathic pain and sympathetic sprouting into the DRG. Pain 72:71–78

    CAS  PubMed  Google Scholar 

  • Rapalino O, Lazarov-Spiegler O, Agranov E et al (1998) Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 4:814–821

    CAS  PubMed  Google Scholar 

  • Rashid MH, Inoue M, Toda K et al (2004) Loss of peripheral morphine analgesia contributes to the reduced effectiveness of systemic morphine in neuropathic pain. J Pharmacol Exp Ther 309:380–387

    CAS  PubMed  Google Scholar 

  • Rittner HL, Labuz D, Schaefer M et al (2006) Pain control by CXCR2 ligands through Ca2+-regulated release of opioid peptides from polymorphonuclear cells. FASEB J 20:2627–2629

    CAS  PubMed  Google Scholar 

  • Rittner HL, Lux C, Labuz D et al (2007) Neurokinin-1 receptor antagonists inhibit the recruitment of opioid-containing leukocytes and impair peripheral antinociception. Anesthesiology 107:1009–1017

    CAS  PubMed  Google Scholar 

  • Rittner HL, Hackel D, Voigt P et al (2009) Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils. PLoS Pathog 5:e1000362

    PubMed  Google Scholar 

  • Rutkowski MD, Pahl JL, Sweitzer S et al (2000) Limited role of macrophages in generation of nerve injury-induced mechanical allodynia. Physiol Behav 71:225–235

    CAS  PubMed  Google Scholar 

  • Schäfers M, Geis C, Brors D et al (2002) Anterograde transport of tumor necrosis factor-alpha in the intact and injured rat sciatic nerve. J Neurosci 22:536–545

    PubMed  Google Scholar 

  • Schäfers M, Geis C, Svensson CI et al (2003a) Selective increase of tumor necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Eur J Neurosci 17:791–804

    PubMed  Google Scholar 

  • Schäfers M, Lee DH, Brors D, Yaksh TL, Sorkin LS (2003b) Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-alpha after spinal nerve ligation. J Neurosci 23:3028–3038

    Google Scholar 

  • Scholz J, Woolf CJ (2002) Can we conquer pain? Nat Neurosci 5:1062–1067

    CAS  PubMed  Google Scholar 

  • Scholz J, Woolf CJ (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10:1361–1368

    CAS  PubMed  Google Scholar 

  • Seltzer Z, Dubner R, Shir Y (1990) A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 43:205–218

    CAS  PubMed  Google Scholar 

  • Shamash S, Reichert F, Rotshenker S (2002) The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci 22:3052–3060

    CAS  PubMed  Google Scholar 

  • Shubayev VI, Myers RR (2001) Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand tracer and TNF receptors. J Neuroimmunol 114:48–56

    CAS  PubMed  Google Scholar 

  • Shubayev VI, Angert M, Dolkas J et al (2006) TNFalpha-induced MMP-9 promotes macrophage recruitment into injured peripheral nerve. Mol Cell Neurosci 31:407–415

    CAS  PubMed  Google Scholar 

  • Simmons DL (2005) Anti-adhesion therapies. Curr Opin Pharmacol 5:398–404

    CAS  PubMed  Google Scholar 

  • Smith FM, Haskelberg H, Tracey DJ et al (2007) Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury. Neuroimmunomodulation 14:317–325

    CAS  PubMed  Google Scholar 

  • Sommer C, Schäfers M (1998) Painful mononeuropathy in C57BL/Wld mice with delayed Wallerian degeneration: differential effects of cytokine production and nerve regeneration on thermal and mechanical hypersensitivity. Brain Res 784:154–162

    CAS  PubMed  Google Scholar 

  • Sommer C, Marziniak M, Myers RR (1998) The effect of thalidomide treatment on vascular pathology and hyperalgesia caused by chronic constriction injury of rat nerve. Pain 74:83–91

    CAS  PubMed  Google Scholar 

  • Sommer C, Petrausch S, Lindenlaub T et al (1999) Neutralizing antibodies to interleukin 1-receptor reduce pain associated behavior in mice with experimental neuropathy. Neurosci Lett 270:25–28

    CAS  PubMed  Google Scholar 

  • Sommer C, Schäfers M, Marziniak M et al (2001) Etanercept reduces hyperalgesia in experimental painful neuropathy. J Peripher Nerv Syst 6:67–72

    CAS  PubMed  Google Scholar 

  • Sorkin LS, Xiao WH, Wagner R et al (1997) Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience 81:255–262

    CAS  PubMed  Google Scholar 

  • Stein C, Kopf A (2009) Anesthesia and treatment of chronic pain. In: Miller RD (ed) Miller’s anesthesia, 7th edn. Churchill Livingstone, Philadelphia, pp 1797–1818

    Google Scholar 

  • Stein C, Lang LJ (2009) Peripheral mechanisms of opioid analgesia. Curr Opin Pharmacol 9:3–8

    CAS  PubMed  Google Scholar 

  • Stein C, Zöllner C (2009) Opioids and sensory nerves. Handb Exp Pharmacol 194:495–518

    CAS  PubMed  Google Scholar 

  • Stein C, Hassan AH, Przewlocki R et al (1990) Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation. Proc Natl Acad Sci USA 87:5935–5939

    CAS  PubMed  Google Scholar 

  • Stein C, Hassan AH, Lehrberger K et al (1993) Local analgesic effect of endogenous opioid peptides. Lancet 342:321–324

    CAS  PubMed  Google Scholar 

  • Stein C, Schäfer M, Machelska H (2003) Attacking pain at its source: new perspectives on opioids. Nat Med 9:1003–1008

    CAS  PubMed  Google Scholar 

  • Stremmel C, Horn C, Eder S et al (2005) The impact of immunological parameters on the development of phantom pain after major amputation. Eur J Vasc Endovasc Surg 30:79–82

    CAS  PubMed  Google Scholar 

  • Tegeder I, Geisslinger G (2004) Opioids as modulators of cell death and survival—unraveling mechanisms and revealing new indications. Pharmacol Rev 56:351–369

    CAS  PubMed  Google Scholar 

  • Thacker MA, Clark AK, Marchand F et al (2007) Pathophysiology of peripheral neuropathic pain: immune cells and molecules. Anesth Analg 105:838–847

    PubMed  Google Scholar 

  • Truong W, Cheng C, Xu QG et al (2003) Mu opioid receptors and analgesia at the site of a peripheral nerve injury. Ann Neurol 53:366–375

    CAS  PubMed  Google Scholar 

  • Uçeyler N, Sommer C (2008) Cytokine regulation in animal models of neuropathic pain and in human diseases. Neurosci Lett 437:194–198

    PubMed  Google Scholar 

  • Uçeyler N, Tscharke A, Sommer C (2007) Early cytokine expression in mouse sciatic nerve after chronic constriction nerve injury depends on calpain. Brain Behav Immun 21:553–560

    PubMed  Google Scholar 

  • Vougioukas VI, Roeske S, Michel U et al (1998) Wallerian degeneration in ICAM-1-deficient mice. Am J Pathol 152:241–249

    CAS  PubMed  Google Scholar 

  • Wagner R, Janjingian M, Myers RR (1998) Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression. Pain 74:35–42

    CAS  PubMed  Google Scholar 

  • Walczak JS, Pichette V, Leblond F et al (2005) Behavioral, pharmacological and molecular characterization of the saphenous nerve partial ligation: a new model of neuropathic pain. Neuroscience 132:1093–1102

    CAS  PubMed  Google Scholar 

  • Walczak JS, Pichette V, Leblond F et al (2006) Characterization of chronic constriction of the saphenous nerve, a model of neuropathic pain in mice showing rapid molecular and electrophysiological changes. J Neurosci Res 83:1310–1322

    CAS  PubMed  Google Scholar 

  • Wall PD, Devor M, Inbal R et al (1979) Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa. Pain 7:103–111

    CAS  PubMed  Google Scholar 

  • Watkins LR, Maier SF (2002) Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 82:981–1011

    CAS  PubMed  Google Scholar 

  • Wenk HN, Brederson JD, Honda CN (2006) Morphine directly inhibits nociceptors in inflamed skin. J Neurophysiol 95:2083–2097

    CAS  PubMed  Google Scholar 

  • Woolf CJ, Ma Q (2007) Nociceptors: noxious stimulus detectors. Neuron 55:353–364

    CAS  PubMed  Google Scholar 

  • Yaksh TL (1988) Substance P release from knee joint afferent terminals: modulation by opioids. Brain Res 458:319–324

    CAS  PubMed  Google Scholar 

  • Zak-Prelich M, McKenzie RC, Sysa-Jedrzejowska A et al (2003) Local immune responses and systemic cytokine responses in zoster: relationship to the development of postherpetic neuralgia. Clin Exp Immunol 131:318–323

    CAS  PubMed  Google Scholar 

  • Zelenka M, Schäfers M, Sommer C (2005) Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain. Pain 116:257–263

    CAS  PubMed  Google Scholar 

  • Zhang X, Bao L, Shi TJ et al (1998) Down-regulation of mu-opioid receptors in rat and monkey dorsal root ganglion neurons and spinal cord after peripheral axotomy. Neuroscience 82:223–240

    CAS  PubMed  Google Scholar 

  • Zuo Y, Perkins NM, Tracey DJ et al (2003) Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain 105:467–479

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Deutsche Forschungsgemeinschaft, Klinische Forschergruppe 100 (MA 2437/1-4; HM).

Author information

Authors and Affiliations

  1. Klinik für Anaesthesiologie und Operative Intensivmedizin, Freie Universität Berlin, Medizinische Fakultät Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Krahmerstr. 6, 12207, Berlin, Germany

    Halina Machelska

Authors
  1. Halina Machelska
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Halina Machelska.

About this article

Cite this article

Machelska, H. Dual Peripheral Actions of Immune Cells in Neuropathic Pain. Arch. Immunol. Ther. Exp. 59, 11–24 (2011). https://doi.org/10.1007/s00005-010-0106-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-010-0106-x

Keywords

Search

Navigation