Zahra Alizadeh; Masoud Fereidoni; Morteza Behnam-Rassouli; Shirin Hosseini
Volume 13, Issue 1 , March 2014, , Pages 19-27
Abstract
Background: Usual dosage of morphine (10 mg/kg) induces analgesia and ultra-low dose (ULD) of morphine (1 μg/kg); hyperalgesia, and C-fibers are also bearing μ- opioid receptors; here the importance of C-fibers on pain and morphine induced analgesia/hyperalgesia is questioned ...
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Background: Usual dosage of morphine (10 mg/kg) induces analgesia and ultra-low dose (ULD) of morphine (1 μg/kg); hyperalgesia, and C-fibers are also bearing μ- opioid receptors; here the importance of C-fibers on pain and morphine induced analgesia/hyperalgesia is questioned and investigated using pain evaluation methods and infant capsaicin treating for C-fibers lesioning.Methods: Wistar male rats (200-250 grams) were assigned to three categories i.e. control, sham (receiving neonatal capsaicin vehicle) and c-lesion (receiving neonatal capsaicin), each one with three groups (n = 7). They were injected intraperitoneally with single dosage of saline, 10 mg/kg or 1 μg/kg morphine, respectively. Thermal pain threshold was evaluated using the tail flick test before and 30 minutes after the injections. Chemical pain was assessed using the formalin test (FT) 30 minutes after the administrations. Results:Results: indicated that thermal (P < 0.001) and chemical pains in both neurogenic and inflammatory phases of FT (P < 0.05) were reduced in C-lesion animals. In the C-normal and C-lesion animals, 10 mg/kg morphine exerted analgesia both in thermal (P < 0.001) and two phases of FT (P < 0.01), but it was more potent in C-lesion animals (P < 0.05). Although ULD of morphine in C-normal animals produced hyperalgesic effect in thermal and chemical pains (P < 0.001), in C-lesion animals, it produced analgesia (P < 0.05) at the neurogenic phase of FT.Conclusion: Results can raise the C-fibers involvement for a significant portion of nociceptive transmission, because C-lesioning potentiated morphine induced analgesia and eliminated ULD of morphine induced hyperalgesia.Therefore C and Aδ fibers can be involved in morphine analgesia; while, just C-fibers are possibly responsible for only presynaptically hyperalgesic/excitatory action of ULD in morphine.
Masoud Fereidoni; Farzaneh Sabouni; Ali Moghimi; Shirin Hosseini
Volume 12, Issue 4 , December 2013, , Pages 129-135
Abstract
Background: Astrocytes are cells within the central nervous system which are activated in a wide spectrum of infections, and autoimmune and neurodegenerative diseases.In pathologic states, they produce inflammatory cytokines, chemokines, and nitric oxide (NO), and sometimes they induce ...
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Background: Astrocytes are cells within the central nervous system which are activated in a wide spectrum of infections, and autoimmune and neurodegenerative diseases.In pathologic states, they produce inflammatory cytokines, chemokines, and nitric oxide (NO), and sometimes they induce apoptosis.Their protease-activated receptors (PARs) can be activated by proteases, e.g.thrombin and trypsin,which are important in brain inflammation.The current study aimed to investigate the effects of different concentrations of trypsin (1 to 100U/ml) on cultured astrocytes.Methods: In the present study, two-day rat infants’ brains were isolated and homogenized after meninges removal, then cultivated in DMEM+10% FBS medium. 10 days later, astrocytes were harvested and recultivated for more purification (up to 95%), using Immunocytochemistry method, in order to be employed for tests. They were affected by different concentrations of trypsin (1, 5, 10, 15, 0, 40, 60, 80, and 100 U/ml). To reveal the inflammation progress, NO concentrations (the Griess test) were assessed after 24 and 48 hours.Results:The results showed that trypsin concentration up to 20 U/ml caused a significant increase in NO, in a dose- dependent manner, on cultured astrocytes (P < 0.001). Trypsin 20 U/ml increased NO production fivefold the control group (P < 0.001). At higher concentrations than 20 U/ml, NO production diminished (P < 0.001). At 100 U/ml, NO production was less than the control group (P < 0.001).Conclusion: Inflammatory effects of trypsin 5-20 U/ml are probably due to the stimulation of astrocytes’ PAR-2 receptors and the increasing of the activation of NF-κB, PKC, MAPKs. Stimulation of astrocytes’ PAR-2 receptors causes an increase in iNOS activation which in turn leads to NO production. However, higher trypsin concentration possibly made astrocyte apoptosis; therefore, NO production diminished. These assumptions need t be further investigated.
