BACKGROUND: Interaction of CD200 with its receptor CD200R has an immunoregulatory role and attenuates various types of neuroinflammatory diseases. METHODS: Immunofluorescence staining, western blot analysis, and RT-PCR were used to investigate the modulatory effects of CD200 fusion protein (CD200Fc) on activation of microglia and astrocytes as well as synthesis of pro- (TNF, IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines in the L4-L5 spinal cord segments in relation to behavioral signs of neuropathic pain after unilateral sterile chronic constriction injury (sCCI) of the sciatic nerve. Withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity were measured in hind paws 1 day before operation; 1, 3, and 7 days after sCCI operation; and then 5 and 24 h after intrathecal application of artificial cerebrospinal fluid or CD200Fc. RESULTS: Seven days from sCCI operation and 5 h from intrathecal application, CD200Fc reduced mechanical and thermal hypersensitivity when compared with control animals. Simultaneously, CD200Fc attenuated activation of glial cells and decreased proinflammatory and increased anti-inflammatory cytokine messenger RNA (mRNA) levels. Administration of CD200Fc also diminished elevation of CD200 and CD200R proteins as a concomitant reaction of the modulatory system to increased neuroinflammatory reactions after nerve injury. The anti-inflammatory effect of CD200Fc dropped at 24 h after intrathecal application. CONCLUSIONS: Intrathecal administration of the CD200R1 agonist CD200Fc induces very rapid suppression of neuroinflammatory reactions associated with glial activation and neuropathic pain development. This may constitute a promising and novel therapeutic approach for the treatment of neuropathic pain.

• MeSH
• antigeny povrchové farmakologie   terapeutické užití   MeSH
• časové faktory MeSH
• CD antigeny metabolismus   MeSH
• cytokiny genetika   metabolismus   MeSH
• fyzikální stimulace škodlivé účinky   MeSH
• gliový fibrilární kyselý protein metabolismus   MeSH
• hyperalgezie farmakoterapie   etiologie   MeSH
• ischialgie komplikace   farmakoterapie   MeSH
• krysa rodu Rattus MeSH
• mícha účinky léků   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• neuroglie účinky léků   metabolismus   MeSH
• orexinové receptory MeSH
• potkani Wistar MeSH
• práh bolesti účinky léků   MeSH
• receptory buněčného povrchu antagonisté a inhibitory   terapeutické užití   MeSH
• regulace genové exprese účinky léků   MeSH
• spinální injekce MeSH
• zánět farmakoterapie   etiologie   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
• antigens, CD200 MeSH Prohlížeč
• antigeny povrchové MeSH
• CD antigeny MeSH
• CD200R1 protein, human MeSH Prohlížeč
• cytokiny MeSH
• gliový fibrilární kyselý protein MeSH
• orexinové receptory MeSH
• receptory buněčného povrchu MeSH

Cannabinoid receptor type 2 (CB2R) plays a critical role in nociception. In contrast to cannabinoid receptor type 1 ligands, CB2R agonists do not produce undesirable central nervous system effects and thus promise to treat neuropathic pain that is often resistant to medical therapy. In the study presented here, we evaluated the bilateral distribution of the CB2R protein and messenger RNA (mRNA) in rat dorsal root ganglia (DRG) after unilateral peripheral nerve injury using immunohistochemistry, western blot, and in situ hybridization analysis. Unilateral chronic constriction injury (CCI) of the sciatic nerve induced neuropathic pain behavior and bilateral elevation of both CB2R protein and mRNA in lumbar L4-L5 as well as cervical C7-C8 DRG when compared with naive animals. CB2R protein and mRNA were increased not only in DRG neurons but also in satellite glial cells. The fact that changes appear bilaterally and (albeit at a lower level) even in the remote cervical DRG can be related to propagation of neuroinflammation alongside the neuraxis and to the neuroprotective effects of CB2R.

• Klíčová slova
• remote neuroinflammation, satellite glial cells, unilateral nerve injury,
• MeSH
• chování zvířat MeSH
• krysa rodu Rattus MeSH
• messenger RNA genetika   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nervus ischiadicus zranění   MeSH
• neuralgie genetika   metabolismus   patologie   MeSH
• potkani Wistar MeSH
• receptor kanabinoidní CB2 genetika   metabolismus   MeSH
• regulace genové exprese * MeSH
• spinální ganglia metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH
• receptor kanabinoidní CB2 MeSH

BACKGROUND: Current research implicates interleukin (IL)-6 as a key component of the nervous-system response to injury with various effects. METHODS: We used unilateral chronic constriction injury (CCI) of rat sciatic nerve as a model for neuropathic pain. Immunofluorescence, ELISA, western blotting and in situ hybridization were used to investigate bilateral changes in IL-6 protein and mRNA in both lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) following CCI. The operated (CCI) and sham-operated (sham) rats were assessed after 1, 3, 7, and 14 days. Withdrawal thresholds for mechanical hyperalgesia and latencies for thermal hyperalgesia were measured in both ipsilateral and contralateral hind and fore paws. RESULTS: The ipsilateral hind paws of all CCI rats displayed a decreased threshold of mechanical hyperalgesia and withdrawal latency of thermal hyperalgesia, while the contralateral hind and fore paws of both sides exhibited no significant changes in mechanical or thermal sensitivity. No significant behavioral changes were found in the hind and fore paws on either side of the sham rats, except for thermal hypersensitivity, which was present bilaterally at 3 days. Unilateral CCI of the sciatic nerve induced a bilateral increase in IL-6 immunostaining in the neuronal bodies and satellite glial cells (SGC) surrounding neurons of both lumbar and cervical DRG, compared with those of naive control rats. This bilateral increase in IL-6 protein levels was confirmed by ELISA and western blotting. More intense staining for IL-6 mRNA was detected in lumbar and cervical DRG from both sides of rats following CCI. The DRG removed from sham rats displayed a similar pattern of staining for IL-6 protein and mRNA as found in naive DRG, but there was a higher staining intensity in SGC. CONCLUSIONS: Bilateral elevation of IL-6 protein and mRNA is not limited to DRG homonymous to the injured nerve, but also extended to DRG that are heteronymous to the injured nerve. The results for IL-6 suggest that the neuroinflammatory reaction of DRG to nerve injury is propagated alongside the neuroaxis from the lumbar to the remote cervical segments. This is probably related to conditioning of cervical DRG neurons to injury.

• MeSH
• ELISA MeSH
• funkční lateralita fyziologie   MeSH
• fyzikální stimulace MeSH
• hybridizace in situ MeSH
• hyperalgezie metabolismus   MeSH
• imunohistochemie MeSH
• interleukin-6 biosyntéza   genetika   MeSH
• krční obratle MeSH
• krysa rodu Rattus MeSH
• lumbosakrální krajina MeSH
• měření bolesti MeSH
• messenger RNA biosyntéza   genetika   MeSH
• nemoci sedacího nervu metabolismus   MeSH
• neuralgie metabolismus   MeSH
• počítačové zpracování obrazu MeSH
• potkani Wistar MeSH
• receptory interleukinu-6 biosyntéza   genetika   MeSH
• spinální ganglia metabolismus   MeSH
• stenóza MeSH
• úžinové syndromy metabolismus   MeSH
• vysoká teplota MeSH
• western blotting 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

It is now clear that a peripheral nerve lesion affects contralateral non-lesioned structures, and thus such a lesion can result in mirror image pain. The pathogenesis is still not exactly known, but there are some possible signaling pathways in the contralateral reaction of the nerve tissue after unilateral nerve injury. Potential signaling pathways of contralateral changes can be generally divided into humoral and neuronal mechanisms. Damage to peripheral nerves or spinal roots produces a number of breakdown products with development of an aseptic inflammatory reaction. Released immunomodulatory cytokines are believed to be transported via blood or cerebrospinal fluid into the contralateral part of the body affecting spinal roots, dorsal root ganglia or peripheral nerves. Because neurons are elements of a highly organized network, injury to the peripheral neuron results in signals that travel transneuronally into the central nervous system and affects the contralateral homonymous neurons. There is also evidence that spinal glia creates and maintain pathological pain. Additionally, there may be compensatory changes in behavior of animals with an impact on contralateral neurons, such as altered stance and motor performance or autonomic reflex changes. Although the transneuronal signaling pathway appears to be plausible, the humoral signaling pathway or other communication systems cannot be excluded at this time. Knowledge about these processes has clinical implications for the understanding of chronic neuropathic pain states, and, therefore, further studies will be necessary. Understanding signaling mechanisms in mirror image pain pathogenesis may provide novel therapeutic targets for the management of neuropathic pain.

• Klíčová slova
• contralateral reaction, cytokines, glia, nerve injury, neurons,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

There is a growing evidence that chemokines and their receptors play a role in inducing and maintaining neuropathic pain. In the present study, unilateral chronic constriction injury (CCI) of rat sciatic nerve under aseptic conditions was used to investigate changes for stromal derived factor-1 (SDF1) and its CXCR4 receptor in lumbal (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) from both sides of naïve, CCI-operated and sham-operated rats. All CCI-operated rats displayed mechanical allodynia and thermal hyperalgesia in hind paws ipsilateral to CCI, but forepaws exhibited only temporal changes of sensitivity not correlated with alterations in SDF1 and CXCR4 proteins. Naïve DRG displayed immunofluorescence for SDF1 (SDF1-IF) in the satellite glial cells (SGC) and CXCR4-IF in the neuronal bodies with highest intensity in small- and medium-sized neurons. Immunofluorescence staining and Western blot analysis confirmed that unilateral CCI induced bilateral alterations of SDF1 and CXCR4 proteins in both L4-L5 and C7-C8 DRG. Only lumbal DRG were invaded by ED-1+ macrophages exhibiting SDF1-IF while elevation of CXCR4-IF was found in DRG neurons and SGC but not in ED-1+ macrophages. No attenuation of mechanical allodynia, but reversed thermal hyperalgesia, in ipsi- and contralateral hind paws was found in CCI-operated rats after i.p. administration of CXCR4 antagonist (AMD3100). These results indicate that SDF1/CXCR4 changes are not limited to DRG associated with injured nerve but that they also spread to DRG non-associated with such nerve. Functional involvement of these alterations in DRG non-associated with injured nerve in neuropathic pain remains to be elucidated.

• MeSH
• biologické markery metabolismus   MeSH
• časové faktory MeSH
• chemokin CXCL12 metabolismus   MeSH
• krysa rodu Rattus MeSH
• makrofágy metabolismus   MeSH
• modely nemocí na zvířatech * MeSH
• nervus ischiadicus zranění   metabolismus   patofyziologie   MeSH
• neuralgie metabolismus   patofyziologie   MeSH
• potkani Wistar MeSH
• receptory CXCR4 antagonisté a inhibitory   metabolismus   MeSH
• spinální ganglia metabolismus   patofyziologie   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
• biologické markery MeSH
• chemokin CXCL12 MeSH
• receptory CXCR4 MeSH

BACKGROUND: There is a growing body of evidence that unilateral nerve injury induces bilateral response, the mechanism of which is not exactly known. Because cytokines act as crucial signaling molecules for response of peripheral nerves to injury, they may be induced to mediate the reaction in remote structures. METHODS: We studied levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) proteins using ELISA in the ipsilateral and contralateral lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) from naïve rats, rats operated on to create unilateral chronic constriction injury (CCI) of the sciatic nerve, and sham-operated rats. Withdrawal thresholds for mechanical allodynia and thermal hyperalgesia were measured in the ipsilateral and contralateral hind and forepaws. RESULTS: The ipsilateral hind paws of all rats operated upon for CCI displayed decreased withdrawal thresholds for mechanical allodynia and thermal hyperalgesia, while no significant behavioral changes were found in the contralateral hind paws and both forepaws. Significantly lower baseline levels of TNF-alpha and IL-10 protein were measured by ELISA in the lumbar than cervical DRG of naïve rats. Bilateral elevation of TNF-alpha was induced in both the lumbar and cervical DRG by unilateral CCI of the sciatic nerve for 7 and 14 days, while the level of IL-10 protein was increased bilaterally in the lumbar DRG 1 and 3 days after operation. IL-10 levels declined bilaterally even below baseline level in both cervical and lumbar DRG 7 days from CCI and normalized after 14 days. In contrast to no significant changes in TNF-alpha, level of IL-10 protein was significantly increased in the ipsilateral lumbar DRG after 3 days and bilaterally in the lumbar DRG after 14 days from sham operation. CONCLUSIONS: The results of our experiments show a bilateral elevation of TNF-alpha and IL-10 not only in the homonymous DRG but also in the heteronymous DRG unassociated with the injured nerve. This suggests that bilaterally increased levels of TNF-alpha and IL-10 in DRG following unilateral CCI are linked with general neuroinflammatory reaction of the nervous system to injury rather than only to development and maintenance of neuropathic pain.

• MeSH
• analýza rozptylu MeSH
• bederní obratle patologie   MeSH
• ELISA metody   MeSH
• funkční lateralita fyziologie   MeSH
• hyperalgezie patofyziologie   MeSH
• interleukin-10 metabolismus   MeSH
• krční obratle patologie   MeSH
• krysa rodu Rattus MeSH
• nemoci sedacího nervu etiologie   patologie   MeSH
• potkani Wistar MeSH
• práh bolesti fyziologie   MeSH
• spinální ganglia patologie   MeSH
• stenóza komplikace   MeSH
• TNF-alfa metabolismus   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
• interleukin-10 MeSH
• TNF-alfa MeSH

The bodies of primary sensory neurons and their satellite glial cells (SGCs) are limited by the basal laminae from extracellular matrix of the dorsal root ganglia (DRG). The basal laminae displayed uniform immunofluorescence staining for laminin-1 in the sections of rat intact (naive) DRG. A proximal or distal ligature of the spinal nerves resulted in a heterogeneous immunostaining for laminin-1 around neuron-SGC units in the sections of the corresponding DRG. The pattern of irregular laminin-1 immunofluorescence was more extensive in the ipsilateral than the contralateral DRG of the operated rats. The immunofluorescence for laminin-1 exactly coincided with binding of Concanavalin-A as well as immunostaining for type IV collagen in both naive DRG and DRG affected by nerve ligature. Nidogen immunostaining decreased or fully disappeared at the surface of the SGCs consistently with immunofluorescence staining for laminin-1, but retained or increased in the endothelial cells and ED-1 positive cells invaded the DRG affected by nerve ligature. The results indicate an alteration of the content of basal laminae surrounding the bodies of primary sensory neurons and their SGSs following nerve constriction injury. A modulation of the basal laminae may be related with other cellular and molecular alterations related with peripheral neuropathic pain, for example, expansion of sympathetic sprouts.

• MeSH
• barvení a značení metody   MeSH
• bazální membrána chemie   MeSH
• ektodysplasiny analýza   MeSH
• fluorescenční protilátková technika metody   MeSH
• kolagen typu IV analýza   MeSH
• konkanavalin A analýza   MeSH
• krysa rodu Rattus MeSH
• laminin analýza   MeSH
• membránové glykoproteiny analýza   MeSH
• neuroglie chemie   patologie   MeSH
• potkani Wistar MeSH
• spinální ganglia chemie   zranění   patologie   MeSH
• stenóza 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
• ektodysplasiny MeSH
• kolagen typu IV MeSH
• konkanavalin A MeSH
• laminin 1 MeSH Prohlížeč
• laminin MeSH
• membránové glykoproteiny MeSH
• nidogen MeSH Prohlížeč