ABSTRACT
Methods@#Male Wistar rats were randomly assigned to five groups (n=10 per group). The clip compression injury model was used to induce chronic central neuropathic pain. Three weeks after SCI, DCPG, siRNA, or normal saline were administered to the intra-ventrolateral PAG region. Withdrawal threshold to the noxious thermal stimulus (e.g., heat hyperalgesia) was assessed through the tail-flick test. In order to assure involvement of this receptor, pain responses were compared with mice that received GRM8 siRNA. @*Results@#We found that the mGluR8 agonist DCPG increased lead to an increased expression of mGluR8 in the PAG region. We also found that SCI can decrease the threshold of response to painful thermal stimuli; however, activation of mGluR8 with DCPG agonist did not significantly improve the tail-flick response. @*Conclusions@#The results revealed that activation of mGluR8 in PAG is not capable of improving the thermal hyperalgesia threshold. Based on the decreased expression of mGluR8 after SCI induced by clip compression injury and its significant increase after treatment of siRNA against mGluR8, this method might still hold promise as an effective treatment of neuropathic pain. It can be concluded that increased expression of mGluR8 is due to the fact that DCPG prevents the death of neurons that express these receptors.
ABSTRACT
Methods@#Male Wistar rats were randomly assigned to five groups (n=10 per group). The clip compression injury model was used to induce chronic central neuropathic pain. Three weeks after SCI, DCPG, siRNA, or normal saline were administered to the intra-ventrolateral PAG region. Withdrawal threshold to the noxious thermal stimulus (e.g., heat hyperalgesia) was assessed through the tail-flick test. In order to assure involvement of this receptor, pain responses were compared with mice that received GRM8 siRNA. @*Results@#We found that the mGluR8 agonist DCPG increased lead to an increased expression of mGluR8 in the PAG region. We also found that SCI can decrease the threshold of response to painful thermal stimuli; however, activation of mGluR8 with DCPG agonist did not significantly improve the tail-flick response. @*Conclusions@#The results revealed that activation of mGluR8 in PAG is not capable of improving the thermal hyperalgesia threshold. Based on the decreased expression of mGluR8 after SCI induced by clip compression injury and its significant increase after treatment of siRNA against mGluR8, this method might still hold promise as an effective treatment of neuropathic pain. It can be concluded that increased expression of mGluR8 is due to the fact that DCPG prevents the death of neurons that express these receptors.
ABSTRACT
BACKGROUND: The present experiment was conducted to identify the cooperative effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral neuropathic pain. METHODS: Chronic constriction injury of the right sciatic nerve was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was inserted into the subarachnoid space. Acetone drops and a 44degrees C water bath were used to evaluate the cold and heat allodynia, respectively. Placing and grasping reflexes were used to assess the locomotor system. RESULTS: SHG at 0.5 and 1 microg significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and 1 microg (P < 0.001) of SHG. 1 microg of noradrenaline, but not 0.5 microg, significantly alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating effect of noradrenaline or SHG disappeared when the two compounds were administrated in equal concentrations. A significant difference (P < 0.01 in the acetone and P < 0.05 in the heat) was observed in the groups under equal doses of the two compounds, with a lower effectiveness of the combination therapy. CONCLUSIONS: Our findings suggest that the simultaneous administrations of noradrenaline and SHG do not result in synergistic analgesia, and combination therapy may not be a good approach to the treatment of chronic neuropathic pain syndrome.
Subject(s)
Acetone , Analgesia , Baths , Constriction , Hand Strength , Hot Temperature , Hyperalgesia , Injections, Spinal , N-Methylaspartate , Neuralgia , Norepinephrine , Reflex , Rodentia , Sciatic Nerve , Serine , Subarachnoid Space , WaterABSTRACT
Objective: In necrotic immature teeth, intra canal medicaments such as triple antibiotic paste [TAP] and calcium hydroxide [CH] are used for root canal disinfection and regeneration treatment. However, the effect of these medicaments on dental pulp fibroblasts has yet to be known. This study aimed to assess the cytotoxicity of CH and TAP against cultured human dental pulp fibroblasts [HDPFs] obtained from third molars
Methods: In this in vitro study, fibroblasts were obtained from the dental pulp of two third molars. Fibroblasts were exposed to 0.1, 1 and 10 mg/mL concentrations of TAP and CH. Six samples were prepared of each medicament and fibroblast viability was evaluated after 72 hours. Data were analyzed using one-way and two-way ANOVA [p<0.001]. The percentage of cell viability was calculated and the cytotoxicity of the medicament was categorized as severe [30%], moderate [30- 60%], mild [60-90%] and non-toxic [>90%]
Results: In TAP samples, only the 10 mg/mL concentration had a significant difference with the control group in terms of the percentage of cell viability and showed moderate cytotoxicity. In CH samples, the 1 and 10 mg/mL concentrations showed significant differences with the control group and were severely cytotoxic
Conclusion: Reduction in cell viability of fibroblasts by increase in concentration was significantly greater in CH compared to TAP group. Thus, in regeneration treatments, these medicaments must be used in concentrations with adequate therapeutic and insignificant adverse effects on fibroblasts