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ObjectiveVentrolateral periaqueductal gray (vlPAG) locates in ascending reticular activating system, which plays a key role in the sleep-wake circle. However, the role of vlPAG in general anesthesia has not been identified. To investigate the effect of the dopamine receptor in vlPAG neurons on propofol anesthesia, we used real-time in vivo fiber photometry, microinjection and EEG.MethodsTo observe the alteration of neuronal activity in the vlPAG throughout propofol anesthesia, 10 Sprague-Dawley rats were used for calcium fiber photometry recording. 50 vlPAG bilateral microinjection models were established and assigned into five groups randomly, including D1R agonist group, D1R antagonist group, D2R agonist group, D2R antagonist group, and control group (n=10). Under propofol anesthesia, 1 μL of D1R agonist, D1R antagonist, D2R agonist, D2R antagonist, and isotonic saline were microinjected into the vlPAG of animals in the corresponding groups, respectively. The induction time, recovery time and the changes in electroencephalogram (EEG) before and after microinjection were recorded and analyzed.ResultsThe neuronal activity in the vlPAG was significantly inhibited during the induction period and markedly recovered during the recovery period from propofol anesthesia (P<0.05). Subsequently, the microinjection of D1R agonist into the vlPAG notably prolonged the induction time and reduced the emergence time of propofol anesthesia with a decrease of δ-band ratio. While the microinjection of D1R antagonist accelerated the induction time and prolonged the emergence time of propofol anesthesia with an increase of δ-band ratio and a decrease in β-band ratio in cortical EEG (P<0.05). The induction and recovery time of D2R agonist /antagonist group did not differ with those of control group. As well, EEG before and after microinjection in D2R agonist /antagonist group did not different.ConclusionThese results indicate that vlPAG modulates the process of propofol anesthesia via D1R.
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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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<p><b>OBJECTIVE</b>To observe descending inhibition of cardiac nociception induced by microinjection of endomorphin-1 (EM1) in the ventrolateral periaqueductal gray (VLPAG) in rats effect and explore the role of μ-opioid receptor in mediating this effect.</p><p><b>METHODS</b>Male SD rats were randomized into electromyography (EMG) group and c-Fos group, both of which were further divided into 5 subgroups, namely 0.9% NaCl group, bradykinin (BK) group, BK+EM1 group, BK+CTOP group, and BK+CTOP+EM1 group. Rat models of cardiac nociception were established by intrapericardial injection of BK. The changes of cardiaosomatic motor reflex induced by BK were observed by assessing EMG responses of the dorsal spinotrapezius muscle; c-Fos expression in the spinal dorsal horn at levels T-T was tested.</p><p><b>RESULTS</b>Compared with 0.9% NaCl, intrapericardial BK injection induced obvious EMG activities and significantly increased c-Fos expression in the spinal dorsal horn at T-T ( < 0.05). Compared with BK injection, microinjection of EM1 in the VLPAG dose-dependently inhibited EMG activities and significantly decreased c-Fos expression ( < 0.05); microinjection of CTOP in the VLPAG produced no significant effect on EMG or c-Fos expression ( > 0.05). Microinjection of CTOP obviously reversed EM1-induced inhibition of EMG activities and c-Fos expression ( < 0.05).</p><p><b>CONCLUSIONS</b>Microinjection of EM1 in the VLPAG produces descending inhibition of cardiac nociception in rats by activating μ-opioid receptor.</p>
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Objective To investigate the role of GABAAα3and GABAB receptors in the ventrolateral periaqueductal gray in the development of paw acute pain in rats.Methods Twelve male SD rats, weighing 280~320 g, were randomly divided into two groups: normal saline group (group NS), formaldehyde-induced pain group (group F), 6 rats in each group.In group F, rats were subcutaneously injected with 2% formaldehyde 50 μl into the ventral surface of right hind paw to induce periphery inflammatory pain.In group NS, rats were subcutaneously injected with normal saline into the ventral surface of right hind paw.Mechanical threshold was assessed using von Frey hairs for every ten minutes.The rat pain behavior scores were recorded for every five minutes.The thickness of skin and skin temperature were recorded for every fifteen minutes.Results Mechanical hyperalgesia were induced in group F after formalin injection into right hind paw.Compared with group NS, rat pain behavior scores were increased significantly in group F at all time points after injection, mechanical threshold were decreased significantly in group F at 10-60 min after injection, the temperature of the skin and the skin thickness were increased significantly in group F at 15-60 min after injection (P<0.05), the levels of the expression of GABAAα3 and GABAB were significantly increased in group F (P<0.05).Conclusion GABAAα3and GABAB receptors mediates formalin-induced hyperalgesia at ventrolateral portion of the PAG (vlPAG) of rats.
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Peripheral nerve injuries are a commonly encountered clinical problem and often result in a chronic pain and severe functional deficits. c-Fos expression is sometimes used as a marker of increased neuronal activity. We have developed herbal bath "HAC" for pain control using the following herbs: Harpagophytum procumbens, Atractylodes japonica, and Corydalis tuber. In the present study, we investigated the effects of herbal bath "HAC" on the recovery rate of the locomotor function and the expression of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region of brain following sciatic crushed nerve injury in rats. Walking track analysis for the evaluation of functional recovery and immunohistochemistry for the c-Fos expression were used for this study. In the present results, characteristic gait change with dropping of the sciatic function index (SFI) was observed and c-Fos expression in the vlPAG was suppressed following sciatic crushed nerve injury in rats. Immersion into herbal bath "HAC" enhanced SFI value and restored c-Fos expression in the vlPAG to the control value. These results suggest that herbal bath "HAC" might activate neurons in the vlPAG, and it facilitates functional recovery from peripheral nerve injury. Here we showed that herbal bath "HAC" could be used as a new therapeutic intervention for pain control and functional recovery from peripheral nerve injury.
Subject(s)
Animals , Rats , Atractylodes , Baths , Brain , Chronic Pain , Corydalis , Gait , Harpagophytum , Immersion , Immunohistochemistry , Neurons , Periaqueductal Gray , Peripheral Nerve Injuries , Track and Field , WalkingABSTRACT
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