title: 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.
abstract: 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.
authors: Central European Institute of Technology (CEITEC), Masaryk University, Kamenice 3, 62500, Brno, Czech Republic. vbrazda@med.muni.cz.
authors: Václav
authors: V
authors: Brázda
authors: Ilona
authors: I
authors: Klusáková
authors: Ivana
authors: I
authors: Hradilová Svíženská
authors: Petr
authors: P
authors: Dubový
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism*; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D009437:Neuralgia / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D020426:Sciatic Neuropathy / Q000235:genetics
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6
references: Exp Neurol. 2012 Jul;236(1):19-27
references: 22504113
references: J Neurosci. 2003 Feb 1;23(3):1026-40
references: 12574433
references: Pain Pract. 2010 May-Jun;10(3):167-84
references: 20384965
references: J Neurosci. 2000 Dec 1;20(23):8637-42
references: 11102468
references: Neurosci Lett. 2011 Aug 26;501(2):86-91
references: 21763399
references: Brain Res Rev. 2007 Nov;56(1):148-69
references: 17706291
references: J Neurosci. 1995 Jul;15(7 Pt 2):5130-8
references: 7623140
references: J Neurosci. 2007 Aug 22;27(34):9068-76
references: 17715343
references: J Neurochem. 2002 Oct;83(1):100-9
references: 12358733
references: Expert Opin Ther Targets. 2006 Aug;10(4):533-46
references: 16848690
references: Trends Neurosci. 2005 Dec;28(12):661-9
references: 16246435
references: Anesth Analg. 2007 Sep;105(3):838-47
references: 17717248
references: Neurosci Lett. 2007 Nov 5;427(2):88-93
references: 17931774
references: Pain Physician. 2011 Jul-Aug;14(4):E343-60
references: 21785485
references: J Leukoc Biol. 2006 Aug;80(2):227-36
references: 16707558
references: Pain. 2000 Apr;85(3):503-521
references: 10781925
references: Bone. 2007 Feb;40(2):360-73
references: 17085092
references: Exp Neurol. 2005 Sep;195(1):61-70
references: 15913608
references: Pharmacol Ther. 2006 Oct;112(1):116-38
references: 16730375
references: Cytokine. 2005 May 21;30(4):154-9
references: 15863388
references: Brain Res. 2000 Oct 6;879(1-2):216-25
references: 11011025
references: Eur J Pharmacol. 2004 Jan 26;484(2-3):183-91
references: 14744602
references: Neuroreport. 1999 Apr 26;10(6):1359-62
references: 10363953
references: Trends Neurosci. 1999 Mar;22(3):122-7
references: 10199637
references: Brain Res Mol Brain Res. 1998 Nov 20;62(2):228-35
references: 9813345
references: J Neuroinflammation. 2013 May 01;10:55
references: 23634725
references: J Exp Med. 1996 Jun 1;183(6):2627-34
references: 8676083
references: Brain Res Brain Res Rev. 2005 Jun;48(3):457-76
references: 15914252
references: Ann Anat. 2009 Jun;191(3):248-59
references: 19403284
references: J Comp Neurol. 2008 Jan 10;506(2):180-93
references: 18022951
references: Brain Res. 1995 Sep 18;692(1-2):123-8
references: 8548295
references: Protein Sci. 1997 May;6(5):929-55
references: 9144766
references: J Histochem Cytochem. 2013 Jul;61(7):529-47
references: 23657829
references: Biochem Biophys Res Commun. 2000 Jan 27;267(3):715-8
references: 10673357
references: Pain. 2004 Jul;110(1-2):299-309
references: 15275780
references: Pain. 1983 Jun;16(2):109-110
references: 6877845
references: Ann Anat. 2011 Jul;193(4):267-75
references: 21458249
references: Development. 1996 Sep;122(9):2847-57
references: 8787758
references: J Neurosci Res. 1999 Feb 15;55(4):411-22
references: 10723052
references: Histochem Cell Biol. 2010 Mar;133(3):323-37
references: 20127490
references: Brain Res. 2003 Sep 12;984(1-2):54-62
references: 12932839
references: Cell Mol Neurobiol. 2009 Sep;29(6-7):1053-62
references: 19330444
references: Trends Neurosci. 1995 Mar;18(3):130-6
references: 7754524
references: J Neuroinflammation. 2010 Feb 10;7:11
references: 20146792
references: Acta Neuropathol. 1979 Apr 12;46(1-2):139-44
references: 452854
references: Annu Rev Immunol. 1997;15:797-819
references: 9143707
references: Dev Neurobiol. 2009 May;69(6):392-400
references: 19280647
references: Prog Brain Res. 2009;175:125-37
references: 19660652
references: Epilepsia. 2002;43 Suppl 5:153-8
references: 12121312
references: Exp Cell Res. 2006 Dec 10;312(20):4019-35
references: 17046748
references: J Neurochem. 1995 Feb;64(2):850-8
references: 7830079
references: J Interferon Cytokine Res. 1996 Sep;16(9):695-700
references: 8887053
references: Eur J Pharmacol. 1993 Oct 5;242(3):229-35
references: 8281987
references: Brain Res. 1978 Sep 8;152(3):429-50
references: 80246
references: Cell Mol Neurobiol. 2006 Oct-Nov;26(7-8):1205-17
references: 16705482
references: Eur J Neurosci. 1999 Jul;11(7):2243-53
references: 10383613
references: Glia. 2004 Jan 1;45(1):105-9
references: 14648551
references: Anesth Analg. 2003 Apr;96(4):1096-1103
references: 12651667
references: Pharmacol Ther. 2006 Jan;109(1-2):57-77
references: 16023729
references: J Pain. 2010 Nov;11(11):1066-73
references: 20627820
references: Neuron Glia Biol. 2010 Feb;6(1):73-83
references: 20519054