Chronic pain is regarded to be one of the common and refractory diseases to cure in the clinic. One hundred Hz electroacupuncture (EA) is commonly used for inflammatory pain and 2 Hz for neuropathic pain possibly by modulating the transient receptor potential vanilloid subtype 1 (TRPV1) or the purinergic P2X3 related pathways. To clarify the mechanism of EA under various conditions of pathological pain, rats received a subcutaneous administration of complete Freund's adjuvant (CFA) for inflammatory pain and spared nerve injury (SNI) for neuropathic pain. The EA was performed at the bilateral ST36 and BL60 1 d after CFA or SNI being successfully established for 3 consecutive days. The mechanical hyperalgesia test was measured at baseline, 1 d after model establishment, 1 d and 3 d after EA. The co-expression changes, co-immunoprecipitation of TRPV1 and P2X3, and spontaneous pain behaviors (SPB) test were performed 3 d after EA stimulation. One hundred Hz EA or 2Hz EA stimulation could effectively down-regulate the hyperalgesia of CFA or SNI rats. The increased co-expression ratio between TRPV1 and P2X3 at the dorsal root ganglion (DRG) in two types of pain could be reduced by 100Hz or 2Hz EA intervention. While 100Hz or 2Hz EA was not able to eliminate the direct physical interaction between TRPV1 and P2X3. Moreover, EA could significantly inhibit the SPB induced by the co-activation of peripheral TRPV1 and P2X3. All results indicated that EA could significantly reduce the hyperalgesia and the SPB, which was partly related to inhibiting the co-expression and indirect interaction between peripheral TRPV1 and P2X3.

• MeSH
• elektroakupunktura * MeSH
• hyperalgezie metabolismus   patofyziologie   terapie   MeSH
• kationtové kanály TRPV metabolismus   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• neuralgie metabolismus   patofyziologie   terapie   MeSH
• potkani Sprague-Dawley MeSH
• práh bolesti MeSH
• purinergní receptory P2X3 metabolismus   MeSH
• signální transdukce MeSH
• spinální ganglia metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• kationtové kanály TRPV MeSH
• P2rx3 protein, rat MeSH Prohlížeč
• purinergní receptory P2X3 MeSH
• Trpv1 protein, rat MeSH Prohlížeč

Bortezomib (BTZ) is used as a chemotherapeutic agent for the treatment of multiple myeloma. Nevertheless, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. Thus, in this study we examined signaling pathways of interleukin-6 (IL-6) and transient receptor potential ankyrin 1 (TRPA1) in the sensory nerves responsible for neuropathic pain induced by BTZ and further determined if influencing the pathways can improve neuropathic pain. ELISA and western blot analysis were used to examine the levels of IL-6, and IL-6 receptor (IL-6R), TRPA1 and p38-MAPK and JNK signal in the lumbar dorsal root ganglion. Behavioral test was performed to determine mechanical and cold sensitivity in a rat model. Our results showed that systemic injection of BTZ increased mechanical pain and cold sensitivity as compared with control animals. Data also showed that protein expression of TRPA1 and IL-6R was upregulated in the dorsal root ganglion of BTZ rats and blocking TRPA1 attenuated mechanical and cold sensitivity in control rats and BTZ rats. Notably, the inhibitory effect of blocking TRPA1 was smaller in BTZ rats than that in control rats. In addition, a blockade of IL-6 signal attenuated intracellular p38-MAPK and JNK in the sensory neuron. This also decreased TRPA1 expression and alleviated mechanical hyperalgesia and cold hypersensitivity in BTZ rats. In conclusion, we revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ, including IL-6-TRPA1, suggesting that blocking these signals is beneficial to alleviate neuropathic pain during BTZ intervention.

• MeSH
• acetanilidy farmakologie   MeSH
• analgetika farmakologie   MeSH
• bortezomib * MeSH
• chinoxaliny farmakologie   MeSH
• fosforylace MeSH
• inhibitory proteasomu * MeSH
• interleukin-6 antagonisté a inhibitory   metabolismus   MeSH
• JNK mitogenem aktivované proteinkinasy metabolismus   MeSH
• kationtový kanál TRPA1 antagonisté a inhibitory   metabolismus   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nervové receptory účinky léků   metabolismus   MeSH
• neuralgie chemicky indukované   farmakoterapie   metabolismus   patofyziologie   MeSH
• potkani Sprague-Dawley MeSH
• práh bolesti účinky léků   MeSH
• puriny farmakologie   MeSH
• pyraziny farmakologie   MeSH
• receptory interleukinu-6 antagonisté a inhibitory   metabolismus   MeSH
• signální transdukce MeSH
• spinální ganglia účinky léků   metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide MeSH Prohlížeč
• acetanilidy MeSH
• analgetika MeSH
• bortezomib * MeSH
• chinoxaliny MeSH
• Il6 protein, rat MeSH Prohlížeč
• Il6r protein, rat MeSH Prohlížeč
• inhibitory proteasomu * MeSH
• interleukin-6 MeSH
• JNK mitogenem aktivované proteinkinasy MeSH
• kationtový kanál TRPA1 MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• puriny MeSH
• pyraziny MeSH
• receptory interleukinu-6 MeSH
• SC 144 MeSH Prohlížeč
• Trpa1 protein, rat MeSH Prohlížeč

Interleukin-10 prevents transition of a physiological inflammatory reaction to a pathological state that may result in neuropathic pain. We studied bilateral changes of IL-10 protein levels in L4-L5 and C7-C8 dorsal root ganglia (DRG) after a chronic constriction injury (CCI) of either L4-L5 spinal nerves (pCCI) or the sciatic nerve (dCCI). Rats undergoing pCCI or dCCI were left to survive for 1, 3, 7 or 14 d, sham-operated rats for 3 or 14 d. After the survival time, C7-C8 and L4-L5 DRG were removed bilaterally from naïve, operated, and sham-operated rats and IL-10 protein was detected by immunohistochemical staining and measured using ELISA analysis. Unilateral pCCI and dCCI induced a transient bilateral elevation in IL-10 protein level not only in the homonymous lumbar DRG but also in the heteronymous cervical DRG nonassociated with the spinal segments of constricted nerve. Sham operations also induced bilateral elevation of IL-10 protein in both homonymous and heteronymous DRG. Our experiments revealed that the more proximal is a nerve injury the more rapid is the initial increase and slower the subsequent decrease of IL-10 protein level in DRG. Changes of IL-10 protein in DRG nonassociated with damaged nerve could be related to a general neuroinflammatory reaction of the nervous system to injury and thereby promote potential of the DRG neurons for regenerating their axons following a conditioning lesion.

• MeSH
• axony patologie   MeSH
• chronická nemoc MeSH
• interleukin-10 metabolismus   MeSH
• krysa rodu Rattus MeSH
• míšní nervy metabolismus   patologie   MeSH
• modely nemocí na zvířatech MeSH
• nemoci periferního nervového systému metabolismus   patologie   patofyziologie   MeSH
• nemoci sedacího nervu metabolismus   patologie   patofyziologie   MeSH
• nervus ischiadicus metabolismus   patologie   MeSH
• potkani Wistar MeSH
• spinální ganglia metabolismus   patologie   patofyziologie   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

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

There is a growing body of evidence that cytokines contribute to both induction and maintenance of neuropathic pain derived from changes in dorsal root ganglia (DRG), including the activity of the primary sensory neurons and their satellite glial cells (SGC). We used immunofluorescence and in situ hybridization methods to provide evidence that chronic constriction injury (CCI) of the sciatic nerve induces synthesis of interleukin-6 (IL-6) in SGC, elevation of IL-6 receptor (IL-6R) and activation of signal transducer and activator of transcription 3 (STAT3) signalling. Unilateral CCI of the rat sciatic nerve induced mechanoallodynia and thermal hyperalgesia in ipsilateral hind paws, but contralateral paws exhibited only temporal changes of sensitivity. We demonstrated that IL-6 mRNA and protein, which were expressed at very low levels in naïve DRG, were bilaterally increased not only in L4-L5 DRG neurons but also in SGC activated by unilateral CCI. Besides IL-6, substantial increase of IL-6R and pSTAT3 expression occurred in SGC following CCI, however, IL-6R associated protein, gp130 levels did not change. The results may suggest that unilateral CCI of the sciatic nerve induces bilateral activation of SGC in L4-L5 DRG to transduce IL-6 signalling during neuroinflammation.

• MeSH
• cytokinový receptor gp130 genetika   metabolismus   MeSH
• funkční lateralita MeSH
• interleukin-6 genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• měření bolesti MeSH
• messenger RNA metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nemoci sedacího nervu patologie   patofyziologie   MeSH
• neuroglie metabolismus   MeSH
• potkani Wistar MeSH
• receptory interleukinu-6 genetika   metabolismus   MeSH
• regulace genové exprese fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• spinální ganglia patologie   patofyziologie   MeSH
• transkripční faktor STAT3 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
• cytokinový receptor gp130 MeSH
• interleukin-6 MeSH
• messenger RNA MeSH
• receptory interleukinu-6 MeSH
• transkripční faktor STAT3 MeSH

Peripheral neuropathic pain (PNP) frequently occurs as a consequence of nerve injury and may differ depending upon the type of insult and the individual patient. Progress in our knowledge of PNP induction mechanisms depends upon the utilization of appropriate experimental models in rodents based on various types of peripheral nerve lesions. In this review, we draw attention to current knowledge on basic cellular and molecular events in various experimental models used to induce the PNP symptoms. Spontaneous ectopic activity of axotomized and non-axotomized primary sensory neurons, the bodies of which are located in the dorsal root ganglion (DRG), seems to be a key mechanism of PNP induction. The primary sensory neurons are directly affected by nerve injury or indirectly by activated satellite glial cells and adjoining immune cells that release a variety of molecules changing the microenvironment of the neurons. Recently, it has become clear that molecules produced during Wallerian degeneration play an important role not only in axon-promoting conditions distal to nerve injury but also in initiation of neuropathic pain. The molecules, transported by the blood, influence afferent neurons and their axons not only in DRG associated, but also those not directly associated with the injured nerve (i.e., in the contralateral DRG or at different spinal segments). Generally, all experimental PNP models based on a partial injury of peripheral nerve segments contain mechanisms initiated by signal molecules of Wallerian degeneration.

• MeSH
• axony fyziologie   MeSH
• axotomie MeSH
• bolest patofyziologie   MeSH
• modely nemocí na zvířatech MeSH
• nemoci periferního nervového systému patofyziologie   MeSH
• neurony fyziologie   MeSH
• periferní nervy patofyziologie   chirurgie   MeSH
• rychlost toku krve MeSH
• spinální ganglia krevní zásobení   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH