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.
Acetone ; Analgesia ; Baths ; Constriction ; Hand Strength ; Hot Temperature ; Hyperalgesia ; Injections, Spinal ; N-Methylaspartate* ; Neuralgia* ; Norepinephrine* ; Reflex ; Rodentia* ; Sciatic Nerve ; Serine ; Subarachnoid Space ; Water

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.

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.

OBJECTIVES: The association between the spread of infectious diseases and climate parameters has been widely studied in recent decades. In this paper, we formulate, exploit, and compare three variations of the susceptible-infected-recovered (SIR) model incorporating climate data. The SIR model is a well-studied model to investigate the dynamics of influenza viruses; however, the improved versions of the classic model have been developed by introducing external factors into the model. METHODS: The modification models are derived by multiplying a linear combination of three complementary factors, namely, temperature (T), precipitation (P), and humidity (H) by the transmission rate. The performance of these proposed models is evaluated against the standard model for two outbreak seasons. RESULTS: The values of the root-mean-square error (RMSE) and the Akaike information criterion (AIC) improved as they declined from 8.76 to 7.05 and from 98.12 to 93.01 for season 2013/14, respectively. Similarly, for season 2014/15, the RMSE and AIC decreased from 8.10 to 6.45 and from 117.73 to 107.91, respectively. The estimated values of R(t) in the framework of the standard and modified SIR models are also compared. CONCLUSIONS: Through simulations, we determined that among the studied environmental factors, precipitation showed the strongest correlation with the transmission dynamics of influenza. Moreover, the SIR+P+T model is the most efficient for simulating the behavioral dynamics of influenza in the area of interest.
Basic Reproduction Number ; Climate ; Communicable Diseases ; Epidemiology ; Humidity ; Influenza, Human* ; Iran* ; Least-Squares Analysis ; Orthomyxoviridae ; Seasons