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Showing 29 results for Javan

Abolhassan Ahmadiani, Tahereh Jesmani, Mohammad Javan,
Volume 3, Issue 2 (Fall and Winter 1999)
Abstract

  Tolerance and dependence are two main problems that have limited morphine administration as an analgesic drug and they might be as a result of changes in the number and affinity of receptors, dysfunction of adenylate cyclase, impaired coupling between activated µ receptor and K+ channels, and changes in the K+ and Ca2+ channels. There are several reports concerning the role of some of these factors in the occurrence of tolerance and dependence. It has been suggested that KATP channels are involved in morphine-induced analgesia. In this study the effect of a constitutive KATP opening state by chronic administration of minoxidil (a KATP opener) on morphine tolerance and dependence was studied using tail-flick test. A single dose (5 mg/kg) of morphine, but not its chronic administration produced analgesia (p<0.001). In addition single and chronic (2 mg/kg) administration of minoxidil produced analgesia (p<0.0001 vs ethanol) and chronic co-administration of morphine and minoxidil did not reduce morphine tolerance, while It reduced jumping (p<0.01) and weight loss (p<0.05) as signs of dependence. Naloxone did not antagonize minoxidil analgesia. Morphine analgesia was reduced by glibenclamide 2 mg/kg (p<0.001). These results may suggest that co-administration of morphine and minoxidil is able to reduce some dependence signs of morphine. Since this treatment reduced the jumping and weight loss, but not the writhing sign, it is concluded that different mechanisms and sites of action are involved in the development of each of the dependence signs.


Alireza Parvizpour, Abolhassan Ahmadiani, Mohammad Javan, Mohammad Kamalinejad,
Volume 3, Issue 2 (Fall and Winter 1999)
Abstract

  There are several reports on the therapeutic effects of TFG in Iranian traditional medical literature such as antinociceptive, antipyretic, and anti-inflammatory, antidiabetic and antidiuretic effects. The anti-inflammatory and anti-pyretic effects of TFG have been confirmed in experimental models. In the present study, the antinociceptive effect of TFG extract in formalin and tail flick tests and its site of action were investigated on NMRI rats (220 ± 20 g). The TFG extract was administered by three routes, i.e. i.c.v., i.t. and i.p. at different doses. The effect of i.p. administration was also examined in tail flick test. The results showed that i.p. administration of aqueous extract of TFG leaves induced analgesia in tail flick and both phases of formalin test. The i.t. administration at doses of 0.5, 1, 2 and 3 mg/rat showed significant antinociceptive effect in formalin test, however i.c.v. administration of extract had no antinociceptive effect. The results of the present study supported the facts that: 1) TFG extract has antinociceptive effect in first and second phases of formalin and tail flick tests and 2) the site of its action in the first and second phase of formalin test might be at spinal cord and with regard to its anti-inflammatory effect, peripheral mechanisms may be involved in its analgesic effect in the second phase of formalin test.


Mohammad Javan, Fereshteh Motamedi, Abolhasan Ahmadiani, Fatemeh Masoudnia,
Volume 7, Issue 1 (Spring and Summer 2003)
Abstract

It has been reported that morphine tolerance does not develop in the presence of chronic pain. Therefore, this study was conducted to find out whether chronic inflammatory pain is able to eliminate or attenuate the developed tolerance to analgesic effect of morphine and also to investigate the role of lumbar spinal cord as a candidate site for this interaction. Tolerance was induced in adult male NMRI rats using daily injection of morphine at a dose of 20 mg/kg (i.p.) for 4 days, or using daily injection of morphine at a dose of 15 pg/rat (i.t.) for 7 days. Chronic inflammatory pain was induced using 50 µl of 5% formalin, injected into the hind paws. The antinociceptive effect of morphine at a dose of 10 mg/kg on day 5 (for i.p. treated rats) or morphine at a dose of 15 pg/rat on day 8 (for i.t. treared rats) were assessed using tail flick test. The results showed that those animals receiving saline (i.t. or i.p.) have potent analgesia (p<0.001), while animals treated with chronic morphine have only a weak analgesia for i.p. treatment (p<0.05). In addition, animals treated with both repeated morphine and 5% formalin (s.c.) into the hind paw showed potent analgesia (p<0.01). Meanwhile, the developed tolerance was reversed by chronic pain induction in the following days (p<0.01). It is concluded that chronic formalin-induced inflammatory pain, not only could prevent tolerance development, but also is able to reverse the developed tolerance to antinociceptive effect of morphine. Since in i.t.-treated animals, tolerance was induced in lumbar spinal cord level, it can be concluded that chronic formalin-induced inflammatory pain, as a stress (through HPA axis) or as a factor which directly exerts some modulations on pain transmission system, is able to prevent tolerance to analgesic effect of morphine through lumbar spinal cord.
Leila Satarian, Mohammad Javan, Yagoob Fathollahi,
Volume 10, Issue 1 (Spring 2006)
Abstract

Introduction: Several researches have reported that stress is able to inhibit the development of morphine tolerance via activating of Hypothalamic-Pituitary-Adrenal (HPA) axis. In the present study we tried to examine the effect of epinephrine, the product of adrenal medulla, on the development of morphine tolerance. Methods: Analgesic tolerance was induced by intrathecal (i.t.) injection of morphine 15 μg/kg, twice a day for 5 days. To study the effect of epinephrine on morphine tolerance, epinephrine (2, 5, 10 or 20 μg/kg, i.t.) was administrated 20 minutes before morphine injection. Analgesia was assessed using tail flick test. Results: In animals that received combined treatments of morphine and epinephrine in doses 2, 5, 10 or 20 μg/ kg for 5 days, at 6th day, morphine produced a more potent analgesia comparing with animals that received saline and morphine during days 1-5. Following tolerance induction during first 5 days, co-administration of epinephrine and morphine during days 6 – 10 reduced the initial tolerance as it induced potent analgesia on day 11th. Conclusion: Our results showed that i.t. administration of epinephrine is able to inhibit and reverse the analgesic tolerance to morphine. It also suggests the possible role of adrenal medulla and epinephrine in mediating the inhibitory effect of stress and HPA activation of the development of analgesic tolerance to morphine.
Shohreh Movahedi, Mohammad Javan, Abolhassan Ahmadiani,
Volume 10, Issue 2 (Summer 2006)
Abstract

Introduction: Ultra low dose (ULD) morphine induces hyperalgesia which is mediated by excitatory Gscoupled opioid receptors. This study was designed to investigate the development of tolerance to hyperalgesic effect of morphine. Also we attempt to seek possible similarity, in view of Gs proteins, between hyperalgesic effect of ULD and hyperalgesic effect after tolerance to HD. Method: Male Wistar rats weighing 180-220 g were used. All injections were given intra peritoneally. For tolerance induction animals received ULD or HD for 5 days and at the 6th day tail flick test was performed before and 30 min after morphine administration. Effect of pretreatment with ULD on analgesic tolerance was assessed by injection of ULD before HD in 5 consecutive days then TF record was done after HD injection on 6th day. Time interval between injections was 15 minutes. Cross tolerance assay was measured by recording the response to a specified dose in 6th day after 5 days treatment with another dose. Oseltamivir, as a GM1 ganglioside inhibitor, was used for inhibition of Gs signaling. . Results: Our results showed that: 1) tolerance was established after chronic injection of ultra low dose (ULD) of morphine. 2) Pre-treatment by ULD reduced tolerance to therapeutic dose of morphine. 3) Cross tolerance to analgesia was observed after chronic administration of ULD. 4) Combination therapy with oseltamivir blocked hyperalgesia reduced analgesic tolerance and attenuated the development of tolerance to hyperalgesic effect of morphine. Conclusion: The results showed the partially common mechanism for development of tolerance to hyperalgesic and analgesic effect of morphine. Signaling through Gs proteins seems to be a common pathway.
Masoud Fereidoni, Mohammad Javan, Saeed Semnanian, Abolhasan Ahmadiani,
Volume 10, Issue 4 (Winter 2007)
Abstract

Introduction: Different mechanisms are involved in stress induced analgesia (SIA) and hyperalgesia (SIH). Repeated stress induces development of tolerance to SIA. The role of HPA axis and Gs signaling pathway in these effects are investigated in the current study. Methods: Forced swim stress (5 min/day) in water (20±1 ºC) was employed to adult male Wistar rats (200-250 g). The nociceptive threshold was assessed using tail flick test. Adrenalectomized (ADX) rats were also subjected to stress tests. Oseltamivir was used to block Gs signaling pathway. Results: Stress produced analgesia for 1 h (p<0.001) and hyperalgesia during 3-24 h after its induction (p<0.05). Repeated administration of the stress caused tolerance development to SIA and increased SIH recorded at 24 h after each session (p<0.001). Oseltamivir couldn’t reverse the SIH. Dexamethasone produced hyperalgesia from 30 min (p<0.001) to 24 h after its administration (p<0.01). Repeated injection of dexamethasone increased the hyperalgesia recorded at 24 h after treatment (p<0.001). In ADX animals SIA continued for 24 h (p<0.01). Adrenalectomy attenuated the chronic stress-induced SIA tolerance and eliminated SIH. Conclusion: SIH is suggested to be related to adrenal activity which also has a role in SIA tolerance. Upper parts of HPA axis seems to be responsible for SIA. Oseltamivir could not reverse the SIH. Therefore, the Gs signaling pathway activation by opioid system may not be responsible for SIH.
Mehdi Sadegh, Javad Mirnajafi-Zadeh, Mohammad Javan, Yaghoub Fathollahi, Mohammad Mohammad-Zadeh, Ali Jahanshahi, Zahra Deljo,
Volume 11, Issue 1 (Spring 2007)
Abstract

Introduction: Low-frequency stimulation (LFS) has a delaying effect on kindled seizures acquisition. In the present study we examined the role of galanin receptors in the inhibitory effects of LFS on kindled seizures induced by electrical stimulation of perforant path. Methods: Animals were stimulated daily at the AD threshold intensity with a rapid kindling procedure. LFS was applied immediately after cessation of each kindling stimulation. M35 (0.5 and 1.0 nM per site), a nonselective galanin receptor antagonist, was microinjected daily into the dentate gyrus before the beginning of stimulation protocol and behavioral seizure stages and afterdischarge durations were recorded. Results: LFS application had a suppressive effect on the kindling rate. It significantly increased the number of stimulations needed to reach seizure stages 3, 4 and 5. LFS also decreased the cumulative afterdischarge duration during the days of stimulation. Intra-dentate gyrus microinjection of M35 reduced the inhibitory effect of LFS on kindling rate, significantly. Conclusion: These data indicate that galanin receptors may have a role in mediating part of the inhibitory effects of LFS on perforant path kindled seizures.
Ali Shamsizadeh, Vahid Sheibani, Yaghoub Fathollahi, Mohammad Javan, Javad Mirnajafi-Zadeh, Mohammad Reza Afarinesh,
Volume 11, Issue 2 (Summer 2007)
Abstract

Previous studies have shown that the receptive field properties, spontaneous activity and spatio-temporal interactions of low-threshold mechanical somatosensory cells in the barrel cortex are influenced by C-fibers. In this study, we examined the effect of C-fiber depletion on response properties of barrel cortex neurons following experience dependent plasticity. Methods: In this study, exteracellular single unit recording was performed on 154 barrel cortex neurons in 70 male Wistar rats (38-41days old). For depleting of C-fibers, neonatal rats received an intra-peritoneal injection of capsaicin solution (50 mg/kg) on the first neonatal day. For induction of experience dependent plasticity, all whiskers but D2 on the left muzzle, were plucked from first neonatal day. Neuronal ON and OFF responses were recorded in right barrel cortex following principal whisker (PW) and its caudal adjacent whisker (AW) deflection. Results: Whisker plucking increased PW–evoked ON responses both in capsaicin and vehicle treated rats (all P<0.05). In vehicle treated rats, AW-evoked ON responses were decreased in plucked animals (P< 0.05). Of particular interest, in capsaicin treated rats, AW-evoked ON responses were not decreased in plucked animals. Analyzing OFF responses showed similar result to ON responses. Conclusion: These findings indicate that c-fibers can modulate neuronal response properties following experience dependent plasticity in layer IV of barrel cortex.
Jamal Ghorbi, Mohammad Javan, Vahid Sheibani, Leila Satarian, Amir Zarebkohan,
Volume 11, Issue 2 (Summer 2007)
Abstract

There is some evidence supporting the reduced activity of integrins following chronic administration of morphine. This reduction might play a role in morphine tolerance development. Manganese binds to the extracellular domain of integrins and makes them to be activated. The effect of integrins activation using manganese on tolerance development to the analgesic effect of morphine was investigated in this study. Methods: To induce tolerance to analgesic effect of morphine, morphine (15 μg/rat) was injected intrathecally (i.t.) to male adult Wistar rats twice a day for five days. To investigate the effect of manganese, it was injected (20 nmol/rat-i.t.) 15 minutes prior to morphine injections during mentioned period. The analgesic effect of morphine (15 μg/rat) was measured using tail flick test on day 6. Results: The results indicated that in animals which received both manganese and morphine during first 5 days, morphine induced a significant analgesia on day 6. Chronic administration of manganese did not change the pain threshold and morphine induced analgesia. Comparison of morphine analgesia following a single dose of morphine (15 μg/rat) or chronic manganese+morphine, indicated that manganese did not have any effect on the morphine analgesia. Conclusion: Our results showed that, manganese administration prior to morphine is able to prevent morphine tolerance development. It seems that decreased activity of integrins following chronic administration of morphine plays a pivotal role in tolerance development to morphine analgesia. Further investigation needs to determine whether manganese effect is dependent on the integrins role in cell adhesions, or on their intracellular signaling pathways.
Mohammad Mohammad-Zadeh, Javad Mirnajafi-Zadeh, Yaghoub Fathollahi, Mohammad Javan, Parviz Ghorbani,
Volume 11, Issue 2 (Summer 2007)
Abstract

Introduction: Previous studies have been shown that low frequency stimulation (LFS) has an inhibitory effect on kindling acquisition. However, the mechanism of this effect has not been completely determined. In the present study, the effect of LFS of the perforant path on seizures induced by rapid perforant path kindling was investigated. Methods: Animals were kindled by electrical stimulation of perforant path. One group of animals (n=6) received LFS (0.1 ms pulses at 1 Hz, 200 pulse, and 50-150 µA) after termination of each kindling stimulations. In control groups, animals received only kindling stimulations (n=8) or LFS (n=4). Basal field potential recording and paired pulse stimulations were done before kindling stimulations every days. Results: Application of LFS significantly retarded the kindling acquisition and increased the number of stimulations to achieve different seizure stages [F(4,60)=10.9, P<0.0001]. LFS also prevented increment of slope of field excitatory postsynaptic potentials and population spike amplitude during kindling (P<0.001) (There was %88.6±1.7 increment in fEPSP and %94±2.3 increment in PS in kindled group and %3.5±.05 increment in fEPSP and %12.3±0.1 decrease in PS in kindled+LFS group). In addition, LFS prevented the marked increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired pulse depression induced by kindling significantly (P<0.01). Conclusion: According to obtained results, it may be suggested that LFS of perforant path has a significant antiepileptogenic effect on perforant path kindled seizures through inhibition of synaptic transmission in dentate gyrus. Meanwhile, LFS prevents compensatory increase in the paired pulse depression during kindling acquisition.
Zahra Barabadi, Sohrab Hajizadeh, Mohammad Javan, Batool Erfani, Ali Heidarian Pour,
Volume 11, Issue 4 (Winter 2008)
Abstract

Introduction: Endothelium and smooth muscle dysfunction are the most important complications of diabetes. In type 1 diabetic patients, absence of insulin leads to vasoconstriction and lower skin blood perfusion. Release of some mediators by endothelium which is induced by insulin causes vasodilation, but the exact mechanism of insulin vasodilatory effect is not detected properly. At present study we investigated the role of NO as a vasodilator and KATP channels and their intraction in the vasodilatory effect of insulin on the skin vessles. Methods: Male wistar rats (200-250 gr) were made diabetic by streptozocin (50mg/kg, s.c). After 40 days of diabetes induction, skin blood flow was measured by Laser Doppler Flowmetry technique (LDF). Insulin, LNNA (NO blocker) and Glibenclamide (KATP blocker) infusion were made by infusion pump subcutaneousely. Results: 1- Insulin increases skin blood flow in both control and diabetic groups and this increase was significantly higher in diabetic group. 2- Insulin vasodilatory effect was decreased by LNNA. 3- The vasodilatory effect of insulin was decreased by Glibenclamide. 4- Simultaneous block of both NO and KATP was more effective. Conclusion: Insulin induces vasodilation in part by NO release and partly by activation of K ATP channels. However some interaction has been seen between both routes. Although by block of both these routes, blood flow has not been completely inhibited. So it is supposed that other factors may be involved in this effect and yet to be illucidated.
Leila Satarian, Mohammad Javan, Fereshteh Motamedi,
Volume 12, Issue 1 (Spring 2008)
Abstract

Introduction: Stress inhibits the development of tolerance to morphine analgesia via activating Hypothalamic- Pituitary-Adrenal (HPA) axis. Modified catecholamine systems have been reported following morphine tolerance development. In the current study we tried to evaluate changes in the gene expression levels for MAO-A, MAO-B, COMT and thyrosine hydroxylase (TyH) enzymes following chronic pain, development of morphine tolerance and their combined administration. Methods: Analgesic tolerance was induced by intrapritoneal injections of morphine 20 mg/kg twice a day for 4 days. To study the effect of pain on morphine tolerance, 50 μl of formalin 5% was injected into the animal paws prior to morphine injections. Semi-quantitative RT-PCR was used to evaluate the gene expression level in lumbar spinal cord on day 5. Three separate control groups received saline or morphine injections or pain induction. Results: Chronic administration of morphine increased the expression level of MAO-B, decreased the expression of TyH and did not change the expression of COMT and MAO-A. Pain increased the expression of MAO-A, but did not change the expression of MAO-B, COMT and TyH. The combination of morphine treatment and pain induction for 4 days partially reversed the reduced expression of TyH and did not change the expression of MAO-A, MAO-B and COMT. Conclusion: Our results showed that in the context of morphine tolerance, gene expression was changed toward decreased biosynthesis and increased elimination of catecholamines. It seems that chronic administration of morphine caused lower level of catecholamines in spinal neurons and help development of morphine tolerance. Also, chronic pain partially produced compensational changes in gene expression. This may explain for its anti-tolerance effect.
Narges Hoseinmardi, Leila Azimi, Mohammad Javan, Naser Naghdi, Yaghoub Fathollahi,
Volume 13, Issue 2 (Summer 2009)
Abstract

Abstract* Introduction: Chronic morphine exposure can cause addiction and affect synaptic plasticity, but the underlying neural mechanisms of this phenomenon remain unknown. Herein we used electrophysiologic approaches in hippocampal CA1 area to examine the effect of chronic morphine administration on short-term plasticity. Methods: Experiments were carried out on hippocampal slices taken from either control animals or animals made dependent via oral chronic morphine administration. Population spikes (PSs) were recorded from stratum pyramidale of CA1 following stimulation the Schaffer collateral afferents. For examining the short-term synaptic plasticity, paired pulse stimulations with inter pulse interval (IPI) of 10, 20, 80, and 200 ms were applied and paired pulse index (PPI) was calculated. Results: Chronic morphine exposure had no effect on the baseline response. A significant increase in PPI was observed in dependent slices at 80 ms IPI as compared to the control ones. There was no significant difference in baseline response between control and dependent slices when we used long term morphine, naloxone, and both. However, long term morphine administration caused significant difference in PPI at IPI of 20 ms. This effect was eliminated in the presence of naloxone. Conclusion: These findings suggest that morphine dependence could affect short-term plasticity in hippocampal CA1 area and increase the hippocampus network excitability. Keywords: Addiction, CA1 neural networks, short-term synaptic plasticity.
Mojdeh Navidhamidi, Mohammad Javan, Yaghoub Fatholahi, Saeed Semnanian,
Volume 14, Issue 2 (Summer 2010)
Abstract

Introduction: The aim of this study was to assess the effect of Ca2+/calmodulin-dependent kinase IIα (CaMKIIα) inhibitor (KN-93) injection into the locus coeruleus (LC) on the modulation of withdrawal signs. We also sought to study the effect of chronic morphine administration on CaMKIIα activity in the rat LC. Methods: The research was based on behavioral and molecular studies. In the behavioral study, we cannulated the LC with stereotaxic surgery and after 7 days of recovery, injections of KN-93, KN-92 (inactive analogue of KN-93) or DMSO (vehicle) was performed. Morphine and saline were injected in control groups. In the molecular study, we assessed the amount of phosphorylated CaMKIIα (pCaMKIIα) protein expression in LC nucleus using western blot technique. Results: Behavioral study There was a significant difference in withdrawal signs between KN-93 and morphine dependent groups (P<0.05). No significant difference was observed between KN-92 and morphine dependent groups and also between DMSO and morphine dependent groups. Molecular study Morphine and control groups and also morphine and naloxone groups showed significant differences in the level of pCaMKIIα (P<0.05). There was no significant difference between control and naloxone groups. Conclusion: Chronic morphine administration can increase the amount of CaMKIIα activity in LC nucleus and inhibition of this enzyme can decrease some withdrawal signs in dependent rats.
Maryam Zeraati, Javad Mirnajafi-Zadeh, Mohammad Javan, Saeed Semnanian, Simin Namvar,
Volume 14, Issue 2 (Summer 2010)
Abstract

Introduction: Considering high prevalence of epileptic disease and considering that 40 percent of epileptic patients are resistant to drug therapy, it needs more researches to find new therapeutic ways. LFS is among the new methods for epilepsy treatments. One possible mechanism involved in the anticonvulsant effect of LFS is increased adenosine. Therefore, in this study the role of adenosine production from ATP by ectonucleotidase enzyme pathway in exerting the anticonvulsant effects of LFS were evaluated. Methods: Animals were kindled by electrical stimulation of perforant path in a rapid kindling manner (12 stimulation per day). One group of animals received LFS after kindling stimulation. In one another group, AOPCP a blocker of ectonucleotidase inhibitor was micro injected (50 micro molar) intra cerebro ventricular each day before LFS stimulation. Some group of animals were also received AOPCP (50 and 100 micro molar) but were not applied to LFS. Seizure behavior and electrophysiological parameters (including ADD and field potential) were recorded. Results: Like previous investigations, application of LFS, decreased all seizure parameters significantly. Microinjection of AOPCP had no significant effect on anticonvulsant actions of LFS. However microinjection of AOPCP at doses of 100 micro molar in animals that received just kindling stimulations, increased the seizure parameters significantly. Conclusion: The results show that adenosine production via ectonucleotidase enzyme pathway may has no role in anticonvulsant effects of LFS however endogenous adenosine produced through this pathway has an important role in kindling development.
Jamal Ghorbi, Mohammad Javan, Vahid Sheibani, Amir Zarebkohan,
Volume 14, Issue 2 (Summer 2010)
Abstract

Introduction: In order to study the alterations of beta 1 and 2 integrins mRNA level in rat lumbar spinal cord following the induction of chronic pain and its effect on the development of tolerance to morphine analgesia, we examined the level of expression of these genes in the presence of chronic pain, which is an inhibitor of morphine tolerance. We used induction of chronic pain alone and in combination with morphine administration. Methods: In order to induce tolerance to analgesic effect of morphine, morphine (15 μg/rat) was intrathecally (i.t.) injected to male adult Wistar rats twice a day for 4 days. Chronic pain was induced using formalin %5, 15 minutes before morphine injections during days 1-4. The analgesic effect of morphine was measured using tail flick test. Lumbar spinal tissues were assayed for the expression of beta-1 and 2 integrins using ‘‘semi-quantitative RT-PCR’’ and were normalized to beta-actin. Results: Chronic administration of morphine for 4 days developed tolerance to morphine analgesia. Concomitant induction of pain with morphine administration inhibited the development of tolerance to the analgesic. Induction of chronic pain, 15 minutes before morphine injections resulted in significant increases in beta-1 and 2 integrins mRNA levels. Furthermore, chronic pain alone also resulted in increased beta-1 and 2 integrins mRNA. Conclusion: Our results showed that, the induction of chronic pain prior to morphine administration, which is able to prevent morphine tolerance, increases the expression of integrins. Chronic morphine administration resulted in increases of beta 1 and 2 integrins mRNA level in lumbar spinal cord. It may be suggested that increases of beta-1 and 2 integrins mRNA is the result of the negative feedback of integrin inhibition by chronic morphine administration. Chronic pain is an enhancer of beta-1 and 2 integrins and its simultaneous presence with morphine administration results in increased beta-1 and 2 integrins and as a result prevents the development of morphine tolerance.
Roghaieh Khakpay, Saeed Semnanian, Mohammad Javan, Mahyar Janahmadi,
Volume 14, Issue 3 (Fall 2010)
Abstract

Introduction: Estradiol is a neuroactive steroid, which is found in several brain areas such as locus coeruleus (LC). Estradiol modulates nociception by binding to its receptors and also by allosteric interaction with other membranebound receptors like glutamate and GABAA receptors. LC is involved in noradrenergic descending pain modulation. Methods: In order to study the effect of 17β-estradiol on both acute and persistent pain modulation and its mechanisms, formalin was injected into the hind paw of male rats. Formalin-induced responses including licking and flexing duration and paw jerking frequency were recorded for 60 min after injection of 50 μl of 2% formalin. Also, the expression of α2 and γ1 subunits of GABAA receptor genes were examined by RT-PCR technique. Results: The results of the current study showed that intra-locus coeruleus injection of 17β-estradiol attenuated the second phase, but not the acute phase of formalin induced pain (P< 0.05). GABAA receptor antagonist (bicuculline) reversed the antinociceptive effect of 17β-estradiol, but the expression level of α2 and γ1 subunits of GABAA receptor genes were not significantly changed. Conclusion: It may be concluded that the analgesic effect of 17β-estradiol in formalin induced inflammatory pain is possibly mediated through the interaction with membrane-bound GABAA receptors, however this effect is not exerted at the gene expression level.
Simin Namvar, Javad Mirnajafi-Zadeh, Mohammad Javan, Maryam Zeraati,
Volume 14, Issue 3 (Fall 2010)
Abstract

Introduction: Application of low-frequency stimulation (LFS) is a new method for treatment of drug resistant epileptic patients. Previous studies demonstrated that activation of receptors coupled to Gi proteins is one of the mechanisms of the anticonvulsant effect of LFS. Thus, in this study, alterations in the expression of RGS4 and RGS10 proteins, as negative regulators of Gi proteins, were investigated. Methods: Animals were kindled by perforant path stimulation in a rapid kindling manner (12 stimulation per day, 1 ms pulse duration at 50 Hz). LFS (8 stimulation per day, 0.1 ms pulse duration at 1 Hz, 200 pulses) was applied to the perforant path 5 minute after the termination of kindling stimulations. After electrophysiological recordings for 6 days, the dentate gyrus of the animals was removed and RGS4 and RGS10 protein expression was studied by western blotting technique. Results: Application of LFS significantly retarded kindling acquisition and increased the number of stimulations to achieve different stages of seizure. LFS also significantly reduced after discharge duration. In addition, application of LFS after kindling stimulation reduced the expression of RGS4 and RGS10 proteins. Conclusion: Results of the present study showed that LFS has anticonvulsant effects on the perforant path kindling. Application of LFS following kindling stimulation reduced the expression of RGS4 and RGS10 proteins. Reduction of the expression of these proteins results in the longer activation of signaling pathways of Gi proteins, which may be responsible for LFS anticonvulsant effects.
Masoumeh Kourosh Arami, Saeed Semnanian, Mohammad Javan, Sohrab Hajizadeh, Abdolrahman Sarihi,
Volume 14, Issue 4 (Winter 2011)
Abstract

Introduction: In the present work, spontaneous postsynaptic currents were assessed to investigate the postnatal development of excitatory postsynaptic currents in locus coeruleus neurons. Methods: In this study, AMPA and NMDA receptor-mediated spontaneous synaptic currents in the neurons of locus coeruleus were assessed using whole cell voltage-clamp recording during the first three weeks. Results: The frequency and amplitude of NMDA sEPSCs and the frequency of AMPA sEPSCs were increased in the second and third postnatal weeks compared with these parameters recorded in the first postnatal week. However, the ratio of the AMPA to NMDA current frequency and amplitude was constant until the 3rd postnatal week. Conclusion: These findings suggest that a vast majority of nascent glutamatergic synapses express both functional AMPA and NMDA receptors in the postnatal locus coeruleus, so that AMPA/NMDA sEPSCs remained constant during this period.
Fereshteh Pourabdolhossein, Sabah Mozafari, Mohammad Javan, Sied Javad Mirnajafizadeh, Abolhassan Ahmadiani,
Volume 14, Issue 4 (Winter 2011)
Abstract

Introduction: Demyelination is one of the main causes of neurological disability. It is the end product of numerous pathological processes, multiple sclerosis (MS) being the most common cause. More than 70% of the MS patients suffer from optic disturbances. This disease commonly affects the optic pathway, particularly the optic nerves and chiasm. Several attempts have been made to produce a suitable model of demyelination in optic apparatus up to now. Methods: Local demyelination model was generated using direct injection of lysolecithin (LPC) into the optic chiasm of C57/BLJ6 mice without any undesirable distributions of gliotoxin into other brain structures. Histological and electrophysiological assessments of the processes of demyelination and remyelination in the animal model were done with specific myelin staining and visual evoked potential (VEP) recordings. Results: In this study, both electrophysiological and histological results demonstrated that maximum level of demyelination was observed on day 7 post lesion and an incomplete yet significant remyelination took place on day 14 post lesion. Conclusion: Results showed a relatively rapid endogenous myelin repair in mice optic chiasm. Furthermore, this report might offer a new tool to address possible involvement of new origins of myelin-forming cells and subsequently their manipulation to promote myelin repair in the adult central nervous system.

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