Effects of Ozone on Hippocampus BDNF and Fos Expressions in Rats with Chronic Compression of Dorsal Root Ganglia.

The effects of ozone on hippocampal expression levels of brain-derived neurotrophic factor (BDNF) and c-fos protein (Fos) were evaluated in rats with chronic compression of dorsal root ganglia (CCD). Forty-eight adult female Sprague-Dawley rats were randomly divided into the following 4 groups (n = 12): sham operation (sham group), CCD group, CCD with 20 µg/ml of ozone (CCD + AO3 group), and CCD with 40 µg/ml of ozone (CCD + BO3 group). Except the sham group, unilateral L5 dorsal root ganglion (DRG) compression was performed on all other groups. On days 1, 2, and 4 after the operation, the CCD + AO3 and CCD + BO3 groups were injected with 100 µl of ozone with concentrations of 20 and 40 µg/ml, respectively. Thermal withdrawal latencies (TWLs) and mechanical withdrawal thresholds (MWTs) were measured at various time points before and after the operation. BDNF and Fos expressions were examined in the extracted hippocampi using immunohistochemistry. The TWLs and MWTs of CCD model rats that received ozone were lower with decreased BDNF and increased Fos expression levels, on day 21 after the operation, compared to those of the sham group (P < 0.05). The TWLs and MWTs of the CCD + AO3 and CCD + BO3 groups were higher with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD group (P < 0.05). The TWLs were longer and the MWTs were higher in the CCD + BO3 group at each time point with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD + AO3 group (P < 0.05). Our results revealed that ozone can relieve the neuropathic pain caused by the pathological neuralgia resulting from DRG compression in rats. The mechanism of action for ozone is likely associated with changes in BDNF and Fos expression levels in the hippocampus.

Effect of morphine and a low dose of ketamine on the T cells of patients with refractory cancer pain in vitro.

The combination of morphine and ketamine is considered safe and efficacious in many patients. However, a considerable number of immunomodulatory effects have been reported to be produced by both morphine and ketamine. The aim of the present study was to assess the direct effect of morphine and a low dose of ketamine on the T cells of patients with refractory cancer pain in vitro. Venous blood was obtained from patients with refractory cancer pain and peripheral blood mononuclear cells were isolated using the Ficoll-Hypaque density gradient method. Anti-CD3 beads were used to isolate T cells by positive selection. Subsequently, the T cells were treated with vehicle, 200 ng/ml of morphine or 200 ng/ml of morphine + 100 ng/ml ketamine for 24 h, following which the cells were stimulated with anti-CD3 and anti-CD28. Flow cytometric analysis of CD3+ T cells, and interleukin (IL)-2 and interferon (IFN)-γ in the supernatant, reverse transcription-quantitative PCR analysis for the detection of IL-2 and IFN-γ and western blotting for the detection of p65 nuclear factor (NF)-κB were performed. In vitro, the CD4+ and CD8+ T cell counts, CD4+/CD8+ ratio, secretion of IL-2 and IFN-γ in the supernatant, mRNA expression levels of IL-2 and IFN-γ and expression of p65 NF-κB were significantly decreased following treatment with morphine and morphine + ketamine, compared with results in the control group (all P<0.05). However, there was no significant difference between treatment with morphine and that with morphine + ketamine. Treatment with morphine + ketamine in vitro decreased the immune functions of patients with refractory cancer pain, although the effect of treatment with morphine and a low dose of ketamine did not differ significantly from that with morphine treatment alone.

Resolvin D2 Relieving Radicular Pain is Associated with Regulation of Inflammatory Mediators, Akt/GSK-3ß Signal Pathway and GPR18.

Neuroinflammation induced by protruded nucleus pulposus (NP) has been shown to play a significant role in facilitation of radicular pain. Resolvin D2 (RvD2), a novel member of resolvin family, exhibits potent anti-inflammatory, pro-resolving and antinociceptive effects. But the effect of RvD2 in radicular pain remains unknown. The radicular pain rat models were induced by application of NP to L5 dorsal root ganglion. Each animal received intrathecal injections of vehicle or RvD2 (10 ng µl-1 or 100 ng µl-1). Mechanical thresholds were determined by measuring the paw withdrawal threshold for 7 days. The expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-ß1 (TGF-ß1) in ipsilateral lumbar segment of rat spinal dorsal horns were measured by using ELISA and real time-PCR. Western blot was used to measure the expressions of phosphorylated Akt (p-Akt) and phosphorylated glycogen synthase kinase 3 beta (p-GSK-3ß). The expressions and distributions of RvD2 receptor, G-protein-coupled receptor 18 (GPR18), were also explored in the spinal cord of rats by using double-label immunofluorescence. RvD2 treatment caused significant reductions in the intensity of mechanical hypersensitivity and spinal expressions of TNF-α and IL-6. Meanwhile, RvD2 increased the expressions of TGF-ß1 and regulated Akt/GSK-3ß signaling. Furthermore, immunofluorescence showed that GPR18 colocalized with neurons and astrocytes in spinal cord. The results suggested that RvD2 might attenuate mechanical allodynia via regulating the expressions of inflammatory mediators and activation of Akt/GSK-3ß signal pathway. RvD2 might offer a hopeful method for radicular pain therapy.

The effect of intraperitoneal chemotherapy on early pain hyperalgesia in patients following elective laparoscopic transabdominal resection of rectal cancer.

BACKGROUND: Chemotherapy has been associated with hyperalgesia. This prospective study was designed to investigate the effect of intraperitoneal chemotherapy with lobaplatin on post-operative pain intensity and sufentanil requirements after laparoscopic transabdominal resection of rectal cancer. METHODS: Eighty subjects (40 subjects treated with intraperitoneal chemotherapy and 40 subjects without chemotherapy treatment) scheduled for laparoscopic transabdominal resection of rectal cancer were included in this study. All subjects received standardized anesthetic and patient-controlled analgesia using sufentanil for 72 h post-surgery, as the only analgesics. Pain intensity scores, cumulative sufentanil requirements and side effects were recorded until 72 h post-surgery. RESULTS: Following intraperitoneal chemotherapy, patients had a significantly higher total post-operative sufentanil requirement (193 µg vs. 142 µg; P = 0.008), significantly higher verbal rating scale post-surgery pain intensity scores at rest and with coughing (P < 0.05), and a significantly worse functional activity score (P < 0.05) over 72 h, compared with those without intraperitoneal chemotherapy. There were no post-operative differences in the incidence of side-effects (post-operative nausea [P = 0.189], vomiting [P = 0.311], pruritus [P = 0.263], respiratory depression [P = 1.000], and dizziness [P = 0.712]) between the two groups. CONCLUSION: Intraperitoneal chemotherapy is associated with significantly increased post-operative sufentanil requirements and pain intensity, suggesting chemotherapy-associated hyperalgesia.

Sesamol attenuates oxidative stress, apoptosis and inflammation in focal cerebral ischemia/reperfusion injury.

The aim of the present study was to evaluate the therapeutic potential of sesamol treatment on focal ischemia/reperfusion (I/R) injury in the rat brain. The results demonstrated that pretreatment with sesamol seven days prior to focal cerebral I/R injury had significant positive effects, including improvements in neurological deficits (P<0.05), and a reduction in malondialdehyde content and elevation of antioxidant levels (superoxide dismutase, glutathione and glutatione peroxidase; both P<0.05). Furthermore, levels of B cell lymphoma-2 (Bcl-2)-associated X protein and caspase-3 were significantly downregulated, whereas the level of Bcl-2 was effectively increased. Conversely, the mRNA expression of proinflammatory cytokines were significantly reduced in focal cerebral I/R injury rats upon sesamol intervention. Therefore, the beneficial effects of sesamol on cerebral I/R injury may be due to the reduction of oxidative stress, inhibition of apoptosis and inflammation. The findings of the present study suggest that sesamol supplementation may serve as potent adjuvant in the treatment of focal cerebral ischemia/reperfusion injury due to its neuroprotective effects.

Monocyte chemoattractant protein-1 contributes to morphine tolerance in rats with cancer-induced bone pain.

Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain.

Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats.

PURPOSE: Phosphodiesterase inhibitors possess anti-inflammatory properties. In addition, some studies report that phosphodiesterase 2A (PDE2A) are highly expressed in the dorsal horn of the spinal cord. The present study aimed to investigate whether intrathecal administration of Bay 60-7550, a specific PDE2A inhibitor, could alleviate mechanical allodynia in non-compressive lumbar disc herniation (NCLDH) rats. METHODS: Rat NCLDH models by autologous nucleus pulposus implantation to dorsal root ganglion were established. Vehicle or Bay 60-7550 (0.1, 1.0 mg/kg) was injected by intrathecal catheter at day 1 post-operation. The ipsilateral mechanical withdrawal thresholds were analyzed from the day before surgery to day 7 after surgery. At day 7 post-operation, the ipsilateral lumbar (L4-L6) segments of the spinal dorsal horns were removed, and tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) expressions were measured by ELISA. Furthermore, PDE2A mRNA and protein expressions in spinal cord were measured by Real-Time PCR and Western blot. RESULTS: Intrathecal administration of the PDE2A inhibitor Bay 60-7550, significantly attenuated mechanical allodynia, down-regulated spinal TNF-α, IL-1ß and IL-6 over-expressions, increased the expression of spinal cAMP, as well as cGMP in a more remarkable manner, and decreased the spinal PDE2A expression in NCLDH rats in a dose-dependent manner. CONCLUSIONS: Bay 60-7550 alleviated mechanical allodynia and inflammation in NCLDH rats, which might be associated with increased cAMP and especially cGMP increase. Thus, spinal PDE2A inhibition might represent a potential analgesic strategy for radiculopathy treatment in non-compressive lumbar disc herniation.

Inhibition of spinal UCHL1 attenuates pain facilitation in a cancer-induced bone pain model by inhibiting ubiquitin and glial activation.

The present study examined alterations of spinal ubiquitin C-terminal hydrolase L1 (UCHL1), ubiquitin expression and glial activation in the cancer-induced bone pain rats. Furthermore, whether inhibition of spinal UCHL1 could alleviate cancer-induced bone pain was observed. The CIBP model was established by intrathecal Walker 256 mammary gland carcinoma cells in SD rats. The rats of CIBP developed significant pain facilitation in the Von Frey test. Double immunofluorescence analyses revealed that in the spines of CIBP rats, ubiquitin co-localized with NeuN, Iba-1 or GFAP; UCHL1 and NeuN were co-expressed and UCHL1 also co-localized with ubiquitin. The CIBP model induced up-regulation of ubiquitin and UCHL1 in the spines, as well as glial activation. Inhibition of spinal UCHL1 attenuated pain facilitation by down-regulation of ubiquitin expression and glial activation. in the CIBP rats. Our data suggests that UCHL1/ubiquitin distributed and increased in the spines of CIBP rats, that glial activation also increased in the CIBP model and that inhibition of spinal UCHL1 may be an effective method to alleviate cancer-induced bone pain.

Resolvin D1 Inhibits Mechanical Hypersensitivity in Sciatica by Modulating the Expression of Nuclear Factor-κB, Phospho-extracellular Signal-regulated Kinase, and Pro- and Antiinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion.

BACKGROUND: Accumulating evidence indicates that spinal inflammatory and immune responses play an important role in the process of radicular pain caused by intervertebral disk herniation. Resolvin D1 (RvD1) has been shown to have potent antiinflammatory and antinociceptive effects. The current study was undertaken to investigate the analgesic effect of RvD1 and its underlying mechanism in rat models of noncompressive lumbar disk herniation. METHODS: Rat models of noncompressive lumber disk herniation were established, and mechanical thresholds were evaluated using the von Frey test during an observation period of 21 days (n = 8/group). Intrathecal injection of vehicle or RvD1 (10 or 100 ng) was performed for three successive postoperative days. On day 7, the ipsilateral spinal dorsal horns and L5 dorsal root ganglions (DRGs) were removed to assess the expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-10, and transforming growth factor-ß1 (TGF-ß1) and the activation of nuclear factor-κB (NF-κB)/p65 and phospho-extracellular signal-regulated kinase (p-ERK) signaling (n = 30/group). RESULTS: The application of nucleus pulposus to L5 DRG induced prolonged mechanical allodynia, inhibited the production of IL-10 and TGF-ß1, and up-regulated the expression of TNF-α, IL-1ß, NF-κB/p65, and p-ERK in the spinal dorsal horns and DRGs. Intrathecal injection of RvD1 showed a potent analgesic effect, inhibited the up-regulation of TNF-α and IL-1ß, increased the release of IL-10 and TGF-ß1, and attenuated the expression of NF-κB/p65 and p-ERK in a dose-dependent manner. CONCLUSIONS: The current study showed that RvD1 might alleviate neuropathic pain via regulating inflammatory mediators and NF-κB/p65 and p-ERK pathways. Its antiinflammatory and proresolution properties may offer novel therapeutic approaches for the management of neuropathic pain.

Activation of spinal NF-κB/p65 contributes to peripheral inflammation and hyperalgesia in rat adjuvant-induced arthritis.

OBJECTIVE: It is known that noxious stimuli from inflamed tissue may increase the excitability of spinal dorsal horn neurons (a process known as central sensitization), which can signal back and contribute to peripheral inflammation. However, the underlying mechanisms have yet to be fully defined. A number of recent studies have indicated that spinal NF-κB/p65 is involved in central sensitization, as well as pain-related behavior. Thus, the aim of this study was to determine whether NF-κB/p65 can facilitate a peripheral inflammatory response in rat adjuvant-induced arthritis (AIA). METHODS: Lentiviral vectors encoding short hairpin RNAs that target NF-κB/p65 (LV-shNF-κB/p65) were constructed for gene silencing. The spines of rats with AIA were injected with LV-shNF-κB/p65 on day 3 or day 10 after treatment with Freund's complete adjuvant (CFA). During an observation period of 20 days, pain-related behavior, paw swelling, and joint histopathologic changes were evaluated. Moreover, the expression levels of spinal tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), and cyclooxygenase 2 (COX-2) were assessed on day 14 after CFA treatment. RESULTS: The presence of peripheral inflammation in rats with AIA induced an increase in NF-κB/p65 expression in the spinal cord, mainly in the dorsal horn neurons and astrocytes. Delivery of LV-shNF-κB/p65 to the spinal cord knocked down the expression of NF-κB/p65 and significantly attenuated hyperalgesia, paw edema, and joint destruction. In addition, spinal delivery of LV-shNF-κB/p65 reduced the overexpression of spinal TNFα, IL-1ß, and COX-2. CONCLUSION: These findings indicate that spinal NF-κB/p65 plays an important role in the initiation and development of both peripheral inflammation and hyperalgesia. Thus, inhibition of spinal NF-κB/p65 expression may provide a potential treatment to manage painful inflammatory disorders.

Histone deacetylase inhibitors trichostatin A and suberoylanilide hydroxamic acid attenuate ventilator-induced lung injury.

The pathophysiology of ventilator-induced lung injury (VILI) involves multiple mechanisms including inflammation. Histone deacetylase inhibitors have been shown to exert anti-inflammation activity. The purpose of this study was to examine the protecting roles and mechanisms of the histone deacetylase inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) in ventilator-induced lung injury in normal rat lung. Male Sprague-Dawley rats were divided into four groups: lung-protective ventilation (LV), injurious ventilation (HV), HV+TSA and HV+ SAHA groups. Mechanical ventilation (MV) settings were 7 ml/kg VT and 3cm H2O positive end-expiratorypressure [PEEP], 40 breaths/min for LV group and 42 ml/kg VT, zero end-expiratoryvolume [ZEEP], 40 breaths/min for the HV, HV+TSA and HV+ SAHA groups. After 2 h of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio and the activity of myeloperoxidase (MPO) were determined. The concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-10 (IL-6) in the homogenized lung were measured by ELISA. The expression ICAM-1 was measured by both realtime PCR and Western blot assays. In addition, survival of each group was also assessed. Our results indicated that administration of TSA or SAHA alleviated ventilator-induced lung injury. This was accompanied by reduced neutrophil infiltration, reduced MPO activity, decreased intercellular adhesion molecule-1 (ICAM-1) expression in lung tissue, and lower TNF-alpha, IL-1beta and IL-6 levels. In addition, treatment with HDAC inhibitors significantly prolonged the survival time of ventilator-induced lung injury rats. Our data suggested that TSA and SAHA could significantly alleviate ventilator-induced rat lung injury and prolong the survival time of those rats by attenuate intrapulmonary inflammatory response.

WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6).

BACKGROUND: Toll-like receptors (TLRs) play a pivotal role in the defense against invading pathogens by detecting pathogen-associated molecular patterns (PAMPs). TLR4 recognizes lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, resulting in the induction and secretion of proinflammatory cytokines such as TNF-α and IL-6. The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) regulates a variety of cellular biological processes. Here, we investigated whether WWP1 acts as an E3 ubiquitin ligase in TLR-mediated inflammation. METHODOLOGY/RESULTS: Knocking down WWP1 enhanced the TNF-α and IL-6 production induced by LPS, and over-expression of WWP1 inhibited the TNF-α and IL-6 production induced by LPS, but not by TNF-α. WWP1 also inhibited the IκB-α, NF-κB, and MAPK activation stimulated by LPS. Additionally, WWP1 could degrade TRAF6, but not IRAK1, in the proteasome pathway, and knocking down WWP1 reduced the LPS-induced K48-linked, but not K63-linked, polyubiquitination of endogenous TRAF6. CONCLUSIONS/SIGNIFICANCE: We identified WWP1 as an important negative regulator of TLR4-mediated TNF-α and IL-6 production. We also showed that WWP1 functions as an E3 ligase when cells are stimulated with LPS by binding to TRAF6 and promoting K48-linked polyubiquitination. This results in the proteasomal degradation of TRAF6.

Treatment of lumbar intervertebral disc herniation using C-arm fluoroscopy guided target percutaneous laser disc decompression.

OBJECTIVE: To evaluate the safety and therapeutic efficacy of target percutaneous laser disc decompression (T-PLDD) for the treatment of lumbar disc herniation. BACKGROUND DATA: PLDD using the Nd:YAG laser has been regarded as an effective alternative treatment for disc herniation. However, all the previous studies were concentrated on vaporizing the nucleus pulposus in the intervertebral space. We hypothesize that insertion of the needle into the extruded part of the nucleus pulposus will decrease its volume and provide superior clinical effects compared to therapies that decrease the volume of the intradiscal nucleus pulposus. MATERIALS AND METHODS: A total of 25 patients suffering from posterolateral extruded but nonsequestered lumbar intervertebral disc herniation were treated with T-PLDD. After treatment, the patients were followed up and the therapeutic effect was assessed at 1, 3, 6, and 12 months using the modified MacNab criteria. RESULTS: The success rate was 80.0% (18 of 25), 88.0% (22 of 25), 92.0% (23 of 25), and 92.0% (23 of 25) at 1, 3, 6, and 12 months respectively. No serious complications occurred in any of the patients. Furthermore, we did not observe any neurological sequelae. CONCLUSIONS: T-PLDD can significantly decrease pain and improve function of patients who have extruded but nonsequestered lumbar intervertebral disc herniation.

[Expression of NF-kappaB and TNF-alpha in spinal dorsal horn in a rat model of neuropathic pain].

OBJECTIVE: To investigate the expressions of NF-kappaB and TNF-alpha in lumbar spinal cord in a rat model of chronic constrictive injury (CCI). METHODS: Seventy-six male SD rats were randomly divided into 2 groups (n = 38 each): CCI group receiving chronic constriction injury and sham group receiving sham operation as control. The mechanical and thermal nociceptive thresholds were assessed with paw withdrawal latency (PWL) to von Frey filaments and radiant heat at different time points. Five animals were sacrificed at each time point for real-time polymerase chain reaction (real-time PCR) and another three animals sacrificed at 7 d post-operation for double-immunofluorescence histochemical staining. Lumbar segments of spinal cord were removed. The expressions of NF-kappaB and TNF-alpha in spinal cord were examined by real-time PCR and double-immunofluorescence histochemical technique. RESULTS: The post-operative thresholds to mechanical and thermal stimuli decreased obviously. As compared with contralateral side and sham group, the expressions of NF-kappaB and TNF-alpha mRNA increased significantly in ipsilateral spinal dorsal horn. Their expressions began to increase at 4 d post-operation and peaked at 7 d. Then TNF-alpha began to decrease while NF-kappaB maintained at a high level throughout the experiment. Double-immunofluorescence histochemical staining revealed extensive co-localization of NF-kappaB with TNF-alpha on ipsilateral side of dorsal horn. CONCLUSION: The activation of NF-kappaB and its downstream inflammatory mediators may be involved in the regulation of neuropathic pain.

[Effect of electroacupuncture on the expression of spinal glial fibrillary acidic protein, tumor necrosis factor-alpha and interleukin-1beta in chronic neuropathic pain rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of spinal glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in chronic constriction injury (CCI) rats. METHODS: Seventy-two SD rats were randomized into sham operation (sham), CCI (model) and EA groups (n = 24/group). The mechanical and thermal pain thresholds were measured by using Von Frey filaments and radiant-heat irridiation separately. The immunoactivity of GFAP of spinal dorsal horn (L4-L5) was assessed by immunohistochemistry, and the expression of spinal TNF-alpha mRNA and IL-1beta mRNA was detected by real time-PCR. RESULTS: Compared with pre-CCI and sham group, both mechanical and thermal pain thresholds decreased considerably in rats with CCI (P < 0.05), and in comparison with model group, those of EA group increased markedly (P < 0.05). Compared with sham group, GFAP immunoactivity (mainly in the lamina I-II of the spinal dorsal horn), TNF-alpha mRNA and IL-1beta mRNA expression in the ipsilateral spinal cord on the CCI side in model group increased considerably (P < 0.05), while compared with model group, the expression of GFAP, TNF-alpha mRNA and IL-1beta mRNA in EA group was down-regulated remarkably (P < 0.05). CONCLUSION: EA can effectively suppress CCI-induced up-regulation of expression of spinal GFAP, TNF-alpha mRNA and IL-1beta mRNA, which may contribute to its effect in reducing mechanical allodynia and thermal hyperalgesia in neuropathic pain rats.