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Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE
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Protein kinase Cε (PKCε) is a transforming oncogene and plays an important role in many cellular processing. In the present paper, we review the development of experimental researches on the acute-chronic pain transformation. Results indicated that prostaglandin E2 (PGE2) / EP1 receptor-Gq-PKCε is an important signaling pathway to modulate chronic pain in peripheral dorsal root ganglion (DRG) neurons, and also plays a role in the later stage of hyperalgesia during transformation from acute to chronic pain. PKCε in DRG neurons induces mechanical and thermal hypersensitivity respectively by over expression of transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin-1 (TRPA1), further mediating the transformation from acute to chronic pain. Whereas, PGE2-evoked activation of EP1-Gq-PKCε signaling may be the key link in initiating the pain translation process through regulating downstream TRPA1 and TRPV1. Electroacupuncture (EA) has been used to effectively relieving various types of acute and chronic pain for decades, and can significantly inhibit the expression of PKCε and its upstream and downstream molecules. Therefore, it can be inferred that there exists a possibility of EA interventions in interfering the transformation from acute to chronic pain by regulating peripheral PKCε signaling pathway.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) on mechanical hyperalgesia threshold (MHTs) and thermal hyperalgesia threshold (THTs) and content of proteinase-activated receptors 2 (PAR 2) in dorsal root ganglia (DRG) in rats with inflammatory pain, so as to explore its peripheral mechanism underlying improvement of inflammatory pain. METHODS: The present study contains two parts. 1) In the first part, 27 male SD rats were randomized into sham hyperalgesic priming (sham-HP) group and real hyperalgesic priming (HP) group (n＝5 in the sham-HP group and n＝6 in the HP group for the test of MHTs, n＝8 in the two groups for the test of THTs). The sham-HP model was established by subcutaneous injection of normal saline into the left plantar part of the hind-paw, and the HP model established by subcutaneous injection of 1% carragenan (the first injection) into the same left hind paw, followed by injection of PGE2 (100 ng/25 μL, the second injection) into the dorsum pedis of the same hind paw 7 days after the first injection. The ipsilateral paw withdrawal latencies (MHTs and THTs) were detected before and 5 h, 3 d and 6 d after the first injection, 0.5, 4 and 24 h after the second injection. 2) In the second part, 64 male SD rats were randomly divided into sham-HP, HP, sham-EA and EA groups (n＝16 in each group). The sham-HP and HP models were made in the same way as the first part. Both"Zusanli"(ST 36)and "Kunlun"(BL 60) were punctured with filiform needles in the sham-EA group and also stimulated with EA: 2 Hz/100 Hz, 0.5－1.5 mA (0.5 mA increase per 10 min) for 30 min in the EA group, 1 time/d for 7 d. Both ipsilateral MHTs and THTs were observed at the same time-points of the first part and the PAR 2 protein content in the L 4－L 6 DRGs was assayed by ELISA 24 h after the second injection. RESULTS: 1) In the first part of the study, compared with the sham-HP group, the MHTs at 5 h and 3 d, and THT at 5 h after the first injection, and MHTs, and THTs at 4 and 24 h after the se-cond injection were significantly decreased in the HP group (P<0.01, P<0.05). 2) In the second part of the study, compared with the HP group, the MHTs at 4 and 24 h after the second injection and the THTs at 3 d after the first injection, 4 and 24 h after the second injection were significantly up-regulated in the EA group (P<0.01, P<0.05). The content of PAR 2 in the DRGs (L 4－L 6) was significantly higher in the HP group than in the sham-HP group (P<0.05), but considerably lower in the EA group than in the HP group (P<0.05). CONCLUSION: EA can suppress hyperalgesia priming in inflammatory pain rats which may be related to its effect in down-regulating PAR 2 level in the lumbar DRGs.
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Objective To investigate the role of CCL2 in pain facilitation and spinal mechanisms in the rat model of bone cancer pain.Methods The bone cancer pain model was developed by inoculating.Walker 256 mammary gland carcinoma cells into the rat tibia medullary cavity.SD female rats were divided into 5 groups randomly ( n =8):sham group( group Ⅰ),sham + CCL2 antibody group( group Ⅱ),BCP group( group Ⅲ),BCP +control lgG group ( group Ⅳ),BCP + CCL2 antibody group ( group Ⅴ ).VonFrey threshold was measured one day before operation and 1 st,3 rd,5th,7th,10th,14th,21 st after operation.CCL2 antibody or control lgG was injected intrathecally from 10th to 12th day.The expression of the spinal Iba-1 ( microglial marker) in rat lumbar4-5 was detected by immunohistochemistry assay.Results From the 10th to 21st day after operation,the PMWT of group Ⅲ rats were ( 1.78 ±0.38)g,( 1.70 ±0.17)g,( 1.35 ±0.07 )g;group Ⅳ rats were (2.99 ±0.67)g,(2.52 ±0.75)g,(1.13±0.07)g ; and group Ⅴ rats were (5.88±0.66)g,(7.81 ±0.75)g,(6.19±0.53)g.Compared with group Ⅲ,the PMWT of group Ⅴ was remarkly higher (P＜0.01) ; group Ⅳ had no obvious statistical significance (P＞0.05).At the 14th day after operation,the MOD of group Ⅲ,Ⅳ and Ⅴ rats were (151.3 ±10.8 ),( 149.2 ± 10.6),(74.5 ± 5.0),Compared with group Ⅲ,the MOD of group Ⅴ was significantly increased (P＜0.01 ),group Ⅳ had no obvious statistical significance (P ＞ 0.05 ).Conclusion Intrathecal injection of CCL2 antibody can remarkly attenuate established pain facilitation of tibial bone cancer pain rats,and significantly suppress the expression of Iba-1.It suggests that CCL2 is involved in the bone cancer pain via activation of spinal microglia.