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Objective The activation of P2X7 receptor in ventrolateral periaqueductal gray (vlPAG) is involved in the formation and maintenance of bone cancer pain (BCP). This study will establish a rat model of BCP and observe the effect of the activation of P2X7 receptor in vlPAG on D-serine level through brain microdialysis combined with ELISA. Methods Forty-two female SD rats were divided into four groups by random number table: normal control group (n=12), sham group (n=12), BCP group (n=12) and P2X7 receptor antagonist group (n= 6). The model of metastatic BCP in the tibias of the rats was established in the BCP group, and 20μL of RPMI-1640 medium cell suspension containing SHZ-88 breast cancer cells was injected (1×107 cancer cells/0.5 mL). The sham group was injected with treated cancer cells of the same volume (SHZ-88 breast cancer cells were kept in boiling water at 90 ℃ for 20 min), and the rest of the operation was the same as the BCP group. The normal control group received no treatment. The P2X7 receptor antagonist group was treated the same as the BCP group, except that the P2X7 receptor-specific antagonist A-438079 was added to the perfusion solution. The thermal pain threshold and mechanical pain threshold were detected at the same time in the normal control group, the sham group and the BCP group. The positive expression of P2X7 receptor in vlPAG of rats was detected by immunohistochemistry in each group in 21 days. The changes of D-serine in vlPAG dialysate were detected by ELISA in each group. Results The mechanical pain threshold and thermal pain threshold of the rats in BCP group on Day 5, 7, 10, 14, 18 and 21 were lower than those of the normal control group and sham group (P<0.01). The positive expression of P2X7 was scattered in vlPAG in normal control group and sham group. The number of P2X7 receptor positive cells in the BCP group was significantly higher than that in the control group and sham group (P<0.01). The content of D-serine in vlPAG of the rats in BCP group [(220.28±63.38)ng/mL] was significantly higher than that in the control group [(148.09±46.89)ng/mL] and the sham group [(147.32±51.44)ng/mL] (P<0.05). The content of D-serine in vlPAG [(134.20±41.77)ng/mL] in P2X7 receptor antagonist group was significantly lower than that in BCP group (P<0.05). Conclusion The activation of the P2X7 receptor in ventrolateral periaqueductal gray promotes D-serine release and participates in the mechanisms of BCP in rats .
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Objective To investigate the expression of γ-aminobutyric acid A receptor α1 subunit (GABAAα1) in the ventrolateral periaqueductal gray (vLPAG) in rats with formalin-induced acute pain. Methods The rats were randomly divided into two groups:control group(group C) and formalin-induced pain group(group F),12 rats in each group:0.9% sodium chloride solution or 2% formaldehyde 50 μL was injected into the ventral surface of right hind paw respectively. The pain scores were recorded for every 5 minutes and the mechanical pain threshold were recorded for every 10 minutes until 1 h. The expression levels of GABAAα1in vLPAG were determined by Western blot analysis in each group.Results The rats in formalin group showed significant nociceptive behaviors immedi-ately, such as paw withdrawal and/or paw licking. Results demonstrated that the rats exhibited a biphasic response to pain. The pain behavior scores in group F were significantly higher than that in group C (P<0.05),and the mechanical pain threshold in group F was decreased after injection compared with group C(P<0.05). The expression of GABAAα1 protein in group F was significantly higher than that in group C (P<0.05).Conclusions The up-regulation of GABAAα1 expression in ventrolateral periaqueductal gray is associated with the decrease of pain threshold in rats with acute pain.
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Aim To observe the effects of propofol on nociceptive response at ventrolateral periaqueductal gray(vlPAG) of rats and the possible role of GABA_A receptor in this prosses.Methods Sprague-Dawley(SD) female rats were randomized into each group.Bicuculline and propofol were microinjected into ventrolateral periaqueductal gray(vlPAG).The noxious response was evaluated by hot plate and formalin test.Fos-like immunoreactivity(FLI) neurons expressed in spinal dorsal horn(DH) induced by formalin intraplantar injection(sc) of one hindpaw were used as a neuroactive marker to observe the effects of propofol on the noxious transmission in DH.Results In hot-plate test,the hyperalgesia induced by propofol(10 g?L~(-1)) vlPAG microinjection was significantly antagonized about(70%),(71%) at 10 and 20 min after (bicu-)culline(25 mg?L~(-1)) vlPAG microinjection(P