Dynamic response to peripheral nerve injury detected by in situ hybridization of IL-6 and its receptor mRNAs in the dorsal root ganglia is not strictly correlated with signs of neuropathic pain

. 2013 Aug 16 ; 9 () : 42. [epub] 20130816

Jazyk angličtina Země Spojené státy americké Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid23953943

BACKGROUND: IL-6 is a typical injury-induced mediator. Together with its receptors, IL-6 contributes to both induction and maintenance of neuropathic pain deriving from changes in activity of primary sensory neurons in dorsal root ganglia (DRG). We used in situ hybridization to provide evidence of IL-6 and IL-6 receptors (IL-6R and gp130) synthesis in DRG along the neuraxis after unilateral chronic constriction injury (CCI) of the sciatic nerve as an experimental model of neuropathic pain. RESULTS: All rats operated upon to create unilateral CCI displayed mechanical allodynia and thermal hyperalgesia in ipsilateral hind paws. Contralateral hind paws and forepaws of both sides exhibited only temporal and nonsignificant changes of sensitivity. Very low levels of IL-6 and IL-6R mRNAs were detected in naïve DRG. IL-6 mRNA was bilaterally increased not only in DRG neurons but also in satellite glial cells (SGC) activated by unilateral CCI. In addition to IL-6 mRNA, substantial increase of IL-6R mRNA expression occurred in DRG neurons and SGC following CCI, while the level of gp130 mRNA remained similar to that of DRG from naïve rats. CONCLUSIONS: Here we evidence for the first time increased synthesis of IL-6 and IL-6R in remote cervical DRG nonassociated with the nerve injury. Our results suggest that unilateral CCI of the sciatic nerve induced not only bilateral elevation of IL-6 and IL-6R mRNAs in L4-L5 DRG but also their propagation along the neuraxis to remote cervical DRG as a general neuroinflammatory reaction of the nervous system to local nerve injury without correlation with signs of neuropathic pain. Possible functional involvement of IL-6 signaling is discussed.

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Chao T, Pham K, Steward O, Gupta R. Chronic nerve compression injury induces a phenotypic switch of neurons within the dorsal root ganglia. J Comp Neurol. 2008;506(2):180–193. doi: 10.1002/cne.21537. PubMed DOI

Ueda H. Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms. Pharmacol Ther. 2006;109(1–2):57–77. PubMed

Hanani M. Satellite glial cells in sensory ganglia: from form to function. Brain Res Brain Res Rev. 2005;48(3):457–476. doi: 10.1016/j.brainresrev.2004.09.001. PubMed DOI

Dubovy P, Tuckova L, Jancalek R, Svizenska I, Klusakova I. Increased invasion of ED-1 positive macrophages in both ipsi- and contralateral dorsal root ganglia following unilateral nerve injuries. Neurosci Lett. 2007;427(2):88–93. doi: 10.1016/j.neulet.2007.09.012. PubMed DOI

DeLeo JA, Colburn RW, Nichols M, Malhotra A. Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. J Interferon Cytokine Res. 1996;16(9):695–700. doi: 10.1089/jir.1996.16.695. PubMed DOI

Dubovy P, Jancalek R, Klusakova I, Svizenska I, Pejchalova K. Intra- and extraneuronal changes of immunofluorescence staining for TNF-alpha and TNFR1 in the dorsal root ganglia of rat peripheral neuropathic pain models. Cell Mol Neurobiol. 2006;26(7–8):1205–1217. PubMed

Simpson RJ, Hammacher A, Smith DK, Matthews JM, Ward LD. Interleukin-6: structure-function relationships. Protein Sci. 1997;6(5):929–955. doi: 10.1002/pro.5560060501. PubMed DOI PMC

Simonato M, Bregola G, Armellin M, Del Piccolo P, Rodi D, Zucchini S, Tongiorgi E. Dendritic targeting of mRNAs for plasticity genes in experimental models of temporal lobe epilepsy. Epilepsia. 2002;43(Suppl 5):153–158. PubMed

Tatard VM, D’Ippolito G, Diabira S, Valeyev A, Hackman J, McCarthy M, Bouckenooghe T, Menei P, Montero-Menei CN, Schiller PC. Neurotrophin-directed differentiation of human adult marrow stromal cells to dopaminergic-like neurons. Bone. 2007;40(2):360–373. doi: 10.1016/j.bone.2006.09.013. PubMed DOI

Hirota H, Kiyama H, Kishimoto T, Taga T. Accelerated nerve regeneration in mice by upregulated expression of interleukin (IL) 6 and IL-6 receptor after trauma. J Exp Med. 1996;183(6):2627–2634. doi: 10.1084/jem.183.6.2627. PubMed DOI PMC

Oka T, Oka K, Hosoi M, Hori T. Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats. Brain Res. 1995;692(1–2):123–128. PubMed

Bolin LM, Verity AN, Silver JE, Shooter EM, Abrams JS. Interleukin-6 production by Schwann cells and induction in sciatic nerve injury. J Neurochem. 1995;64(2):850–858. PubMed

Murphy PG, Grondin J, Altares M, Richardson PM. Induction of interleukin-6 in axotomized sensory neurons. J Neurosci. 1995;15(7 Pt 2):5130–5138. PubMed PMC

Brazda V, Klusakova I, Svizenska I, Veselkova Z, Dubovy P. Bilateral changes in IL-6 protein, but not in its receptor gp130, in rat dorsal root ganglia following sciatic nerve ligature. Cell Mol Neurobiol. 2009;29(6–7):1053–1062. PubMed

Dubovy P, Klusakova I, Svizenska I, Brazda V. Spatio-temporal changes of SDF1 and its CXCR4 receptor in the dorsal root ganglia following unilateral sciatic nerve injury as a model of neuropathic pain. Histochem Cell Biol. 2010;133(3):323–337. doi: 10.1007/s00418-010-0675-0. PubMed DOI

Jancalek R, Dubovy P, Svizenska I, Klusakova I. Bilateral changes of TNF-alpha and IL-10 protein in the lumbar and cervical dorsal root ganglia following a unilateral chronic constriction injury of the sciatic nerve. J Neuroinflamm. 2010;7:11. doi: 10.1186/1742-2094-7-11. PubMed DOI PMC

Taga T, Kishimoto T. Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol. 1997;15:797–819. doi: 10.1146/annurev.immunol.15.1.797. PubMed DOI

Gardiner NJ, Cafferty WB, Slack SE, Thompson SW. Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury. J Neurochem. 2002;83(1):100–109. doi: 10.1046/j.1471-4159.2002.01101.x. PubMed DOI

Habecker BA, Sachs HH, Rohrer H, Zigmond RE. The dependence on gp130 cytokines of axotomy induced neuropeptide expression in adult sympathetic neurons. Dev Neurobiol. 2009;69(6):392–400. doi: 10.1002/dneu.20706. PubMed DOI PMC

Dubovy P, Klusakova I, Svizenska I, Brazda V. Satellite glial cells express IL-6 and corresponding signal-transducing receptors in the dorsal root ganglia of rat neuropathic pain model. Neuron Glia Biol. 2010;6(1):73–83. doi: 10.1017/S1740925X10000074. PubMed DOI

Klusakova I, Dubovy P. Experimental models of peripheral neuropathic pain based on traumatic nerve injuries - an anatomical perspective. Ann Anat. 2009;191(3):248–259. doi: 10.1016/j.aanat.2009.02.007. PubMed DOI

Dubovy P. Wallerian degeneration and peripheral nerve conditions for both axonal regeneration and neuropathic pain induction. Ann Anat. 2011;193(4):267–275. doi: 10.1016/j.aanat.2011.02.011. PubMed DOI

Liu CN, Wall PD, Ben-Dor E, Michaelis M, Amir R, Devor M. Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury. Pain. 2000;85(3):503–521. doi: 10.1016/S0304-3959(00)00251-7. PubMed DOI

Rothwell NJ, Hopkins SJ. Cytokines and the nervous system II: Actions and mechanisms of action. Trends Neurosci. 1995;18(3):130–136. doi: 10.1016/0166-2236(95)93890-A. PubMed DOI

Alexander JK, Popovich PG. Neuroinflammation in spinal cord injury: therapeutic targets for neuroprotection and regeneration. Prog Brain Res. 2009;175:125–137. PubMed

Chiang CY, Wang J, Xie YF, Zhang S, Hu JW, Dostrovsky JO, Sessle BJ. Astroglial glutamate-glutamine shuttle is involved in central sensitization of nociceptive neurons in rat medullary dorsal horn. J Neurosci. 2007;27(34):9068–9076. doi: 10.1523/JNEUROSCI.2260-07.2007. PubMed DOI PMC

Watkins LR, Hutchinson MR, Johnston IN, Maier SF. Glia: novel counter-regulators of opioid analgesia. Trends Neurosci. 2005;28(12):661–669. doi: 10.1016/j.tins.2005.10.001. PubMed DOI

Vallejo R, Tilley DM, Vogel L, Benyamin R. The role of glia and the immune system in the development and maintenance of neuropathic pain. Pain Pract. 2010;10(3):167–184. doi: 10.1111/j.1533-2500.2010.00367.x. PubMed DOI

Vallejo R, Barkin RL, Wang VC. Pharmacology of opioids in the treatment of chronic pain syndromes. Pain Physician. 2011;14(4):E343–E360. PubMed

Watkins LR, Hutchinson MR, Milligan ED, Maier SF. “Listening” and “talking” to neurons: implications of immune activation for pain control and increasing the efficacy of opioids. Brain Res Rev. 2007;56(1):148–169. doi: 10.1016/j.brainresrev.2007.06.006. PubMed DOI PMC

Arruda JL, Sweitzer S, Rutkowski MD, DeLeo JA. Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain. Brain Res. 2000;879(1–2):216–225. PubMed

Ma W, Quirion R. Targeting invading macrophage-derived PGE2, IL-6 and calcitonin gene-related peptide in injured nerve to treat neuropathic pain. Expert Opin Ther Targets. 2006;10(4):533–546. doi: 10.1517/14728222.10.4.533. PubMed DOI

Murphy P, Topilko P, Schneider-Maunoury S, Seitanidou T, Baron-Van Evercooren A, Charnay P. The regulation of Krox-20 expression reveals important steps in the control of peripheral glial cell development. Development. 1996;122(9):2847–2857. PubMed

Arruda JL, Colburn RW, Rickman AJ, Rutkowski MD, DeLeo JA. Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain. Brain Res Mol Brain Res. 1998;62(2):228–235. doi: 10.1016/S0169-328X(98)00257-5. PubMed DOI

De Jongh RF, Vissers KC, Meert TF, Booij LH, De Deyne CS, Heylen RJ. The role of interleukin-6 in nociception and pain. Anesth Analg. 2003;96(4):1096–1103. PubMed

Dubovy P, Brazda V, Klusakova I, Hradilova-Svizenska I. Bilateral elevation of interleukin-6 protein and mRNA in both lumbar and cervical dorsal root ganglia following unilateral chronic compression injury of the sciatic nerve. J Neuroinflammation. 2013;10:55. doi: 10.1186/1742-2094-10-55. PubMed DOI PMC

Yamaguchi H, Ochi M, Mori R, Ryoke K, Yamamoto S, Iwata A, Uchio Y. Unilateral sciatic nerve injury stimulates contralateral nerve regeneration. Neuroreport. 1999;10(6):1359–1362. doi: 10.1097/00001756-199904260-00037. PubMed DOI

Jancalek R, Svizenska I, Klusakova I, Dubovy P. Bilateral changes of IL-10 protein in lumbar and cervical dorsal root ganglia following proximal and distal chronic constriction injury of peripheral nerve. Neurosci Lett. 2011;501(2):86–91. doi: 10.1016/j.neulet.2011.06.052. PubMed DOI

Rose-John S, Scheller J, Elson G, Jones SA. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol. 2006;80(2):227–236. doi: 10.1189/jlb.1105674. PubMed DOI

Thier M, Marz P, Otten U, Weis J, Rose-John S. Interleukin-6 (IL-6) and its soluble receptor support survival of sensory neurons. J Neurosci Res. 1999;55(4):411–422. doi: 10.1002/(SICI)1097-4547(19990215)55:4<411::AID-JNR2>3.0.CO;2-D. PubMed DOI

Koltzenburg M, Wall PD, McMahon SB. Does the right side know what the left is doing? Trends Neurosci. 1999;22(3):122–127. doi: 10.1016/S0166-2236(98)01302-2. PubMed DOI

Molenaar I, Kuypers HG. Cells of origin of propriospinal fibers and of fibers ascending to supraspinal levels. A HRP study in cat and rhesus monkey. Brain Res. 1978;152(3):429–450. doi: 10.1016/0006-8993(78)91102-2. PubMed DOI

Sallmann S, Juttler E, Prinz S, Petersen N, Knopf U, Weiser T, Schwaninger M. Induction of interleukin-6 by depolarization of neurons. J Neurosci. 2000;20(23):8637–8642. PubMed PMC

Svizenska IH, Brazda V, Klusakova I, Dubovy P. Bilateral changes of cannabinoid receptor type 2 protein and mRNA in the dorsal root Ganglia of a rat neuropathic pain model. J Histochem Cytochem. 2013;61(7):529–547. doi: 10.1369/0022155413491269. PubMed DOI PMC

Twining CM, Sloane EM, Milligan ED, Chacur M, Martin D, Poole S, Marsh H, Maier SF, Watkins LR. Peri-sciatic proinflammatory cytokines, reactive oxygen species, and complement induce mirror-image neuropathic pain in rats. Pain. 2004;110(1–2):299–309. PubMed

Milligan ED, Twining C, Chacur M, Biedenkapp J, O’Connor K, Poole S, Tracey K, Martin D, Maier SF, Watkins LR. Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci. 2003;23(3):1026–1040. PubMed PMC

Elson K, Simmons A, Speck P. Satellite cell proliferation in murine sensory ganglia in response to scarification of the skin. Glia. 2004;45(1):105–109. doi: 10.1002/glia.10294. PubMed DOI

Hill CE, Harrison BJ, Rau KK, Hougland MT, Bunge MB, Mendell LM, Petruska JC. Skin incision induces expression of axonal regeneration-related genes in adult rat spinal sensory neurons. J Pain. 2010;11(11):1066–1073. doi: 10.1016/j.jpain.2010.02.001. PubMed DOI PMC

Arvidson B. A study of the perineurial diffusion barrier of a peripheral ganglion. Acta Neuropathol. 1979;46(1–2):139–144. PubMed

Thacker MA, Clark AK, Marchand F, McMahon SB. Pathophysiology of peripheral neuropathic pain: Immune cells and molecules. Anesth Analg. 2007;105(3):838–847. doi: 10.1213/01.ane.0000275190.42912.37. PubMed DOI

Verri WA, Cunha TM, Parada CA, Poole S, Cunha FQ, Ferreira SH. Hypernociceptive role of cytokines and chemokines: Targets for analgesic drug development? Pharmacol Ther. 2006;112(1):116–138. doi: 10.1016/j.pharmthera.2006.04.001. PubMed DOI

Murphy PG, Ramer MS, Borthwick L, Gauldie J, Richardson PM, Bisby MA. Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice. Eur J Neurosci. 1999;11(7):2243–2253. doi: 10.1046/j.1460-9568.1999.00641.x. PubMed DOI

Vissers KC, De Jongh RF, Hoffmann VL, Meert TF. Exogenous interleukin-6 increases cold allodynia in rats with a mononeuropathy. Cytokine. 2005;30(4):154–159. doi: 10.1016/j.cyto.2005.01.008. PubMed DOI

Czlonkowski A, Stein C, Herz A. Peripheral mechanisms of opioid antinociception in inflammation: involvement of cytokines. Eur J Pharmacol. 1993;242(3):229–235. doi: 10.1016/0014-2999(93)90246-E. PubMed DOI

Flatters SJL, Fox AJ, Dickenson AH. Spinal interleukin-6 (IL-6) inhibits nociceptive transmission following neuropathy. Brain Res. 2003;984(1–2):54–62. PubMed

Flatters SJL, Fox AJ, Dickenson AH. Nerve injury alters the effects of interleukin-6 on nociceptive transmission in peripheral afferents. Eur J Pharmacol. 2004;484(2–3):183–191. PubMed

Osamura N, Ikeda K, Ito T, Higashida H, Tomita K, Yokoyama S. Induction of interleukin-6 in dorsal root ganglion neurons after gradual elongation of rat sciatic nerve. Exp Neurol. 2005;195(1):61–70. doi: 10.1016/j.expneurol.2005.03.019. PubMed DOI

Yang P, Wen HZ, Ou S, Cui J, Fan DH. IL-6 promotes regeneration and functional recovery after cortical spinal tract injury by reactivating intrinsic growth program of neurons and enhancing synapse formation. Exp Neurol. 2012;236(1):19–27. doi: 10.1016/j.expneurol.2012.03.019. PubMed DOI

Ryoke K, Ochi M, Iwata A, Uchio Y, Yamamoto S, Yamaguchi H. A conditioning lesion promotes in vivo nerve regeneration in the contralateral sciatic nerve of rats. Biochem Biophys Res Commun. 2000;267(3):715–718. doi: 10.1006/bbrc.1999.2017. PubMed DOI

Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16(2):109–110. doi: 10.1016/0304-3959(83)90201-4. PubMed DOI

Harnicarova A, Kozubek S, Pachernik J, Krejci J, Bartova E. Distinct nuclear arrangement of active and inactive c-myc genes in control and differentiated colon carcinoma cells. Exp Cell Res. 2006;312(20):4019–4035. doi: 10.1016/j.yexcr.2006.09.007. PubMed DOI

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