Electroacupuncture attenuates spinal nerve ligation-induced microglial activation mediated by p38 mitogen-activated protein kinase / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.</p><p><b>METHODS</b>There were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above.</p><p><b>RESULTS</b>SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42 (P<0.01 or P<0.05).</p><p><b>CONCLUSIONS</b>The central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.</p>

Effect of electroacupuncture on phosphorylation of NR2B at Tyr 1742 site in the spinal dorsal horn of CFA rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of electroacupuncture (EA) on phosphorylation of spinal NR2B at Tyr 1742 site in complete Freund's adjuvant (CFA) induced inflammatory pain rats. METHods Forty male Sprague Dawley rats were randomly divided into normal group (N group, n = 10), the model group (CFA group, n = 15), and the EA group (n = 15). The inflammatory pain model was established by subcutaneous injecting CFA (0.1 mL per rat) into the right hind paw. Paw withdrawal thresholds (PWTs) were measured before CFA injection (as the base), as well as at 24 h, 25 h, 3rd day, and 7th day after CFA injection. Phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn at the 3rd day post-injection were detected using immunohistochemical assay.</p><p><b>RESULTS</b>PWTs in the CFA group were significantly lower than those of the N group at every detective time point post-injection (P < 0.01). PWTs were obviously lower in the EA group than in the N group at 24 h post-injection (P < 0.01). It showed increasing tendency, markedly higher than those of the CFA group at 25 h and 3rd day post-injection (P < 0.01). Compared with the N group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats in the CFA group was up-regulated. Compared with the CFA group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats showed a decreasing tendency in the EA group.</p><p><b>CONCLUSION</b>EA might effectively inhibit CFA-induced inflammatory pain possibly associated with down-regulating phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn.</p>

Immediate analgesic effect of electroacupuncture and its regulation mechanism via spinal p-ERK1/2 / 中国针灸

<p><b>OBJECTIVE</b>To observe influence of electroacupuncture (EA) on phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in spinal cord dorsal horn (SCDH) in rats with acute inflammatory pain induced by complete Freund's adjuvant (CFA), further elucidate the immediate analgesic mechanism of EA via cellular signal transduction.</p><p><b>METHODS</b>Fifty-three healthy male SD rats were divided into two batches. The inflammatory pain models of the first batch of 23 rats were established by using CFA. The changes of the paw withdrawal thresholds (PWTs) of rats were observed and positive cells of p-ERK1/2 in affected SCDH were detected by using immunohistochemistry method. The second batch of 30 rats were randomly divided into a blank control group (N group), CFA group and EA group, 10 rats in each group. The rats of CFA group and EA group were induced inflammatory pain by using CFA, and the EA group was treated with EA at 5.5 h after the model establishment. The changes of PWTs and the positive cells of p-ERK1/2 in SCDH were observed.</p><p><b>RESULTS</b>The PWTs of the first batch of rats obviously decreased at 5 h, 3 d, 7 d and 14 d after CFA administration (all P< 0.01). However, the p-ERK1/2 positive cells in affected SCDH only increased at 5 h after CFA-injection and returned to normality at 3 d after the model establishment. In the second batch, compared with that of N group at the same time point, PWTs of rats in both CFA and EA group obviously decreased after the model establishment (both P<0.01). PWTs of rats in EA group which accepted EA treatment once were longer than those before EA treatment and corresponding PWTs in CFA group at the same time point (both P<0.01). Moreover, the numbers of p-ERK1/2 positive cells of affected SCDH increased significantly in CFA group at 6 h after the model establishment (P<0.01), however, which were decreased significantly in EA group (P<0.01).</p><p><b>CONCLUSION</b>Inhibiting ERK1/2 activation of SCDH may be one of the pivotal mechanism of cellular signal transduction of the immediate analgesic effect educed by EA.</p>

A study on correlation of hepatic metastasis of colorectal cancer to vascular endothelial growth factor, angiopoietin-2, and fibronectin / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the correlation of hepatic metastasis of colorectal cancer to vascular endothelial growth factor (VEGF), angiopoietin- 2 and fibronectin (FN).</p><p><b>METHODS</b>The transcription and expression of VEGF, angiopoietin- 2 and FN were detected by semiquantitative reverse transcription- polymerase chain reaction (SQRT- PCR) and immunohistochemical staining in the specimens from sixty patients with colorectal cancer.</p><p><b>RESULTS</b>The mRNA transcription and expression levels of VEGF, angiopoietin- 2 and FN in colorectal cancer tissues were obviously higher than those in paratumor normal tissues P< 0.05. The transcription and expression levels of VEGF were correlated with tumor invasion P< 0.05,Dukes' stage P< 0.05,and lymph node and/or hepatic metastasis P< 0.05. Angiopoietin expression and transcription levels were correlated with tumor differentiation. The expression of FN in extra cellular matrix (ECM) was significantly higher (P< 0.05),whereas ECM in basement membrane was significantly lower in cancer tissues than that in paratumor normal tissues (P< 0.05),which both were correlated with tumor invasion P< 0.05,Dukes' stage P< 0.05,and lymph node metastasis P< 0.05. Absence of FN protein in basement membrane was also correlated with hepatic metastasis.</p><p><b>CONCLUSION</b>Colorectal cancer cells can secrete VEGF and contribute to metastasis and proliferation of tumor by stimulating the growth of tumor vessel. Both of VEGF and angiopoietin- 2 contribute to angiogenesis and the decrease of FN in basement membrane of cancer tissue is an important primary factor of hepatic metastasis.</p>