Abstract
BackgroundG-protein coupled estrogen receptor 30 (GPR30) was proved the specific estrogen receptor relating to mechanical hyperalgesia. Studies have shown that the GABAA receptor subunits α4, β1, and δ in the periaqueductal gray (PAG) neurons promote the descending facilitation system. This study inquired into whether and how GPR30 and GABAA-α4β1δ in the PAG promote preoperative anxiety-induced postoperative hyperalgesia in female rats.MethodsAll the female rats were subjected to the single prolonged stress (SPS) to stimulate preoperative anxiety. Subsequently, mechanical allodynia was evaluated before and after the incision, based on the paw withdrawal mechanical threshold (PWMT). The selective GPR30 agonist G1 and antagonist G15 were locally microinjected into the PAG. The expression of GPR30, protein kinase A (PKA), and GABAA receptor subunits α4, β1, and δ in the PAG neurons were detected using western blotting and immunofluorescence.ResultsBehavioral testing revealed that Group S and Group I decreased the nociceptive threshold levels of PWMT in female rats. PWMT in Group S + I decreased more than that of Group S and Group I. Further, results of western blotting showed the expression of GPR30, PKA, and GABAA α4, β1, and δ subunits significantly up-regulated in Group S + I, and immunofluorescence indicated that the neurons of PAG in Group S + I appeared simultaneously immunopositive for GPR30 and GABAA α4, β1, and δ receptors. After microinjection of G1 into the PAG, female rats with plantar incision continued to exhibit significant hyperalgesia until postoperative 48 h. On the other hand, microinjection of G15 with SPS and plantar incision procedure relieved postoperative hyperalgesia in female rats. Western blotting demonstrated that intra-PAG injection of G15 markedly decreased the GPR30, PKA, and GABAA α4, β1, and δ levels in Group G15 + I.ConclusionsOur results indicate that the GPR30-PKA-GABAAα4β1δ pathway in the PAG promotes preoperative anxiety-induced postoperative hyperalgesia in female rats. This mechanism might be a potential novel therapeutic target for hyperalgesia in females.
Highlights
G-protein coupled estrogen receptor 30 (GPR30) was proved the specific estrogen receptor relating to mechanical hyperalgesia
This study aims to test the hypothesis that preoperative anxiety-induced elevated GPR30 in the periaqueductal gray (PAG) evoked the up-regulation of extrasynaptic α4, β1, and δ GABAA receptor subunits through protein kinase A (PKA), and exacerbated postoperative pain in female rats
Double immunofluorescence staining for co-expression of GPR30 and GABAAα4, GPR30 and GABAAβ1, as well as GPR30 and GABAAδ were observed in Group S + I (Fig. 4a–c)
Summary
G-protein coupled estrogen receptor 30 (GPR30) was proved the specific estrogen receptor relating to mechanical hyperalgesia. Studies have shown that the GABAA receptor subunits α4, β1, and δ in the periaqueductal gray (PAG) neurons promote the descending facilitation system. This study inquired into whether and how GPR30 and GABAA-α4β1δ in the PAG promote preoperative anxiety-induced postoperative hyperalgesia in female rats. Previous studies have demonstrated the positive correlativity between preoperative anxiety and postoperative pain [2]. It has been shown that estrogen-induced mechanical hyperalgesia is produced by selective agonists of the GPR30 receptor, and is inhibited by knockdown of the GPR30 receptor [7]. Given that PAG plays a vital part in the descending pain pathway and emotion response, it is of great importance to explore how this structure mediates anxiety-induced allodynia in females
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
