Nejvíce citovaný článek - PubMed ID 16023729
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.
- MeSH
- hybridizace in situ MeSH
- interleukin-6 genetika MeSH
- krysa rodu Rattus MeSH
- messenger RNA metabolismus MeSH
- modely nemocí na zvířatech MeSH
- nemoci sedacího nervu genetika MeSH
- neuralgie genetika MeSH
- neuroglie metabolismus MeSH
- potkani Wistar MeSH
- receptory interleukinu-6 genetika MeSH
- spinální ganglia metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interleukin-6 MeSH
- messenger RNA MeSH
- receptory interleukinu-6 MeSH
Local intracellular signaling cascades following peripheral nerve injury lead to robust axon regeneration and neuropathic pain induction. Cytokines are classic injury-induced mediators. We used sciatic nerve ligature (ScNL) to investigate temporal changes in IL-6 and its receptor gp130 in both ipsilateral and contralateral lumbal (L4-L5) dorsal root ganglia (DRG). Rats were operated aseptically on unilateral ScNL and allowed to survive for 1, 3, 7, and 14 days. Immunohistochemistry and Western blot analysis were used to determine levels of IL-6 and gp130 in DRG. A distinct increase in immunostaining for IL-6 was found in the neuronal cell bodies of sections through both ipsilateral and contralateral DRG at 1 and 3 days after operation. After 7 and 14 days, the DRG sections displayed only a moderate elevation in immunostaining when compared with sections of naïve DRG. The levels of IL-6 protein increased in both ipsilateral and contralateral lumbal DRG following peripheral nerve injury. The elevation of IL-6 protein was significant in both ipsilateral and contralateral DRG 1, 3, 7, and 14 days after operation. On the other hand, the levels of gp130 receptor did not change significantly. The data provide evidence for changes in IL-6 levels not only in the DRG associated with the damaged nerve but also in those unassociated with nerve injury during the experimental neuropathic pain model.
- MeSH
- cytokinový receptor gp130 metabolismus MeSH
- imunohistochemie MeSH
- interleukin-6 metabolismus MeSH
- krysa rodu Rattus MeSH
- měření bolesti MeSH
- nervus ischiadicus zranění metabolismus patofyziologie MeSH
- spinální ganglia metabolismus MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokinový receptor gp130 MeSH
- interleukin-6 MeSH