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Showing 57 results for Subject: Pain and addiction

Ali Akbar Aliabadi, Hedayat Sahraei, Mehrangiz Sadooghi, Hasan Ghoshooni, Mehrvaz Alaf-Javadi, Seyed Hasan Salimi, Amir Abbas Barzegari,
Volume 10, Issue 1 (4-2006)
Abstract

Introduction: The influence of ascorbic acid on the nicotine-induced conditioned place preference (CPP) and behavioral sensitization was investigated in the present study. Methods: In a pilot study, place conditioning and locomotor activity were investigated after nicotine (0.25, 0.5, 0.75, 1, 1.5 and 2 mg/kg) or ascorbic acid (1, 10, 100 and 1000 mg/kg) administration. Different doses of ascorbic acid in conditioning days or on the test days were used. Behavioral sensitization was induced in animals by daily intraperitoneal administration of nicotine (0.25 mg/kg) for seven cosecutive days followed by one day interval. On 9th day, locomotor activity was induced by ineffective dose of nicotine (0.1 mg/kg). Ascorbic acid was injected 20 min before each injection of nicotine (acquisition of sensitization) or acutely 20 min before a challenge nicotine injection (expression of sensitization). Results: The results showed that intraperitoneal nicotine (1 mg/kg) administration can induce place preference whereas acute administration of the drug induces catalepsy. Administration of ascorbic acid did not induce place preference nor place aversion and also did not change the locomotor activity. Locomotor sensitization in mice was produced by intraperitoneal injection of nicotine (0.25 mg/kg) for 7 consecutive days. On the 9th day of experiments, activity of the mice was recorded after challenge with nicotine (0.1 mg/kg, i.p.). The senisitization was better achived when the ineffective dose of nicotine (0.1 mg/kg) was applied. Administration with ascorbic acid reduced both the acquisition and expression of nicotine-induced CPP. It was shown that ascorbic acid attenuated the acquisition of nicotine sensitization in a dose-independent manner but the expression of nicotineinduced sensitization was not affected by ascorbic acid. Conclusion: We conclude that ascorbic acid may interfere with nicotine-induced place preference and behavioral sensitization.
Leila Satarian, Mohammad Javan, Yagoob Fathollahi,
Volume 10, Issue 1 (4-2006)
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.
Parivash Hafez-Amini, Jamal Shams, Ali Shabahng-Saber-Tehrani, Ali Haeri-Rohani, Kazem Parivar, Vahab Babapour, Hedayat Sahraei,
Volume 10, Issue 2 (3-2006)
Abstract

Introduction: Several investigations have indicated that dopamine D receptors could influence morphine 2 eward. The influence of olanzapine (a D dopamine receptor antagonist) on the morphine-induced conditioned 2 lace preference (CPP) in male and female mice was investigated in the present study. Methods: The effects of olanzapine on the acquisition and expression of morphine CPP in male and female -MRI mice (W: 20-25 g) were investigated in the present study. Resultd: Subcutaneous (s.c.) injection of morphine (1-10 mg/kg, three drug sessions) induced place preference oth in male and female mice. Intraperitoneal (i.p.) administration of olanzapine (0.5-5 mg/kg) induced place version (CPA) in female mice but not in male mice. Administration of olanzapine (1, 2.5, 5 mg/kg, i.p.) reduced oth the acquisition and expression of morphine-induced CPP in male and female mice. However, olanzapine (5 g/kg, i.p.) caused more than 80% mortality in female but not male mice. The effects of olanzapine were reversed y L-arginine (20 mg/kg, i.p.) pre-administration. Conlusion: We conclude that olanzapine reduced morphine effects via different mechanism/s.
Shohreh Movahedi, Mohammad Javan, Abolhassan Ahmadiani,
Volume 10, Issue 2 (3-2006)
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.
Ali Pourmotabbed, Seyed Ershad Nedaei, Entezar Mehrabinasab,
Volume 10, Issue 2 (3-2006)
Abstract

Introduction: It has been reported that oral morphine dependency facilitated formation of spatial learning and memory. In the present study the role of NMDA receptors located in hippocampal CA1 area of morphine dependent rats was studied. Methods: Male rats were divided into 4 groups. Two cannulae were stereotaxically implanted bilaterally into the hippocampal CA1 area. After 5 days recovery, animals received morphine sulfate or sucrose for 30 consecutive days in drinking water. Morris water maze (MWM) studies were performed from day 26 to 30. In the above mentioned days, animals received bilateral intrahippocampal CA1 area injection of 3.7μg/0.5μl D,L-AP5 (NMDA receptors antagonist) or 0.5μl saline, 30 min before daily experimentation. Spatial learning and memory parameters were subjected to the analysis of variance (ANOVA). Results: Morphine dependence potentiated spatial learning and memory parameters using MWM. D,L-AP5 could inhibit formation of spatial learning and memory in both control and dependent group. Conclusion: Activation of NMDA receptors located in hippocampal CA1 area is essential for potentiation of spatial learning and memory in morphine dependence rats.
Jamal Ghorbi, Mohammad Javan, Vahid Sheibani, Leila Satarian, Amir Zarebkohan,
Volume 11, Issue 2 (8-2007)
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.
Taraneh Moini Zanjani, Seyed Naser Ostad, Nariman Mosaffa,
Volume 11, Issue 3 (12-2007)
Abstract

Introduction: Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. In this situation, Hyperalgesia and Allodynia are the results of prostaglandins and cytokines release in the spinal cord. It seems that immune cells play an importat role in the induction and maintenance of chronic pain. Compared to selective CoxII inhibitors, nimesulide, a highly selective CoxII inhibitor, effectively reduced hyperalgesia due to peripherally administration of inflammatory agents like formalin. In this study we investigate the effect of nimesulide on pain behavior and CoxII expression in macrophage and microglial cells in neuropathic pain condition. Methods: Male Wistar rats (n=6, 150-200 g) using Bennet & Xie model of neuropathic pain were divided in different groups:1- CCI saline 2- Sham saline (control), 3- CCI drugs.Nimesulide 1.25,2.5and 5mg/kg were used. 42 º C water for thermal hyperalgesia and Von Frey Filaments for mechanical allodynia, respectively, were used as pain behaviour tests. Experiments were performed on day before and 1,3,5,7,10,14days post injury. At day 14 rats who received nimesulide 5 mg/kg were killed and CoxII was assessed in macrophages and microglial cells. ANOVA and T-test were used for statistical analysis and % of SD control was used for enzyme expression. Results: Nimesulide 2.5,5mg/kg reduced hyperalgesia and allodynia. Nimesulide 5mg/kg also reduced CoxII expression in macrophages and microglial cells compared to CCIsaline group. Conclusion: Nimesulide reduced hyperalgesia due to nerve inflammation. CoxII- induced PGs activates a wide range of immune cells like macrophages and microglia. It seems that nimesulide a highly selective Cox2 inhibitor can reduce effectively chronic inflammatory pain. َ
Mojtaba Dolatshahi-Somesofla, Fereshteh Motamedi, Abolhasan Ahmadiani, Saeed Esmaili-Mahani,
Volume 11, Issue 3 (12-2007)
Abstract

Nimodipine, an L-type calcium channel blocker, can induce analgesia. However, it is not clear that this analgesic effect is at the level of spinal or supraspinal pain pathway. In addition, it has been reported that the analgesic effect of nifedipine, another L-type calcium channel blocker is related to the HPA axis, but there is no report indicating the role of this axis in the analgesic effect of nimodipine. Methods: Analgesia was measured by tail-flick (TF) test involving spinal reflexes and by hot-plate (HP) requiring an intact central nervous system. Assays were done before and 15, 30, 60 and 120 min after drug administration in the intact, sham operated and adrenalectomized rats. To identify the interaction between nimodipine and HPA axis, plasma corticosterone level was measured using the radioimmunoassay. Results: Nimodipine significantly decreased the plasma corticosterone level, and showed significant antinociception in both tests. Adrenalectomy potentiated the analgesic effect of nimodipine which was reversed by corticosterone replacement. Furthermore, nimodipine analgesic effect in ADX rats was more potent in HP test (compared to TF test). Nimodipine, at mentioned doses, did not alter animal’s movement indices in activity monitoring test. Conclusion: Nimodipine involves both spinal and supraspinal sites to control thermal pain transmission in presence of adrenal gland. It seems that there is a mutual interaction between nimodipine and HPA axis, especially at supraspinal levels.
Mahshid Hoseinzadeh, Iran Pouraboli, Mehdi Abbasnejad, Batool Pouraboli,
Volume 11, Issue 4 (1-2008)
Abstract

Abstract: ِIntroduction: The effect of morphine dependency on learning and spatial memory is controversial. So in this study effect of co-administeration of nitric oxide (NO) and morphine in CA3 of hippocampus on learning and spatial memory in morphine dependent rats was investigated. Methods: After anaesthetization of male rats, cannulae implanted bilaterally in CA3 of hippocampus. After recovery period (7 days), morphine dependency induced then animals divided in 6 groups that received 1μl saline (Sham), L-Arginine, L-Name and morphine individually and L-Arginine with morphine or L-Name with morphine individually. Morphine dependency was induced by subcutaneous injection of morphine(10mg/kg first day and 20mg/kg for four days). Last dose of morphine(20mg/kg) was injected daily to maintain morphine dependency during test period (5 days) in morris water maze Results: Results showed that L-Name decreased learning in morphine dependent rats although was ineffective on retention of memory. Morphine did not affect learning and spatial memory. Co-administeration of L-Arginine and morphine not only improved the effect of morphine on learning and memory but also promote the effect of L-Arginine on learning and spatial memory. Conclusion: Thus co-administeration of NO and morphine in morphine dependent rats can improve learning and spatial memory differently from using them individually.
Javad Sajedianfard, Faramarz Azarang, Elahe Solimannejad,
Volume 12, Issue 1 (5-2008)
Abstract

Introduction: Pain as a complex process in central nervous system (CNS) has been studied by many researchers. Pain is controlled by several CNS pathways, one of the most important of which, is the descending noradrenergic system. This system begins from locus coeruleus (LC) nucleus in pons and ends in the spinal cord. In this research, the effect of pain induced by formalin was studied. Methods: Male Sprague-Dawley rats weighing 280-320 g were categorized into two groups of control (injection of 50 μl normal saline) and test (injection of 50 μl 2.5% formalin). Rats were anesthetized by pentobarbital sodium (50 mg/kg i.p.). Microdialysis probes were inserted 24 hrs before the test was done. Rats were anesthetized by urethane and formalin test for induction of chemical and tonic pain was performed on the hind paw of the animals. Micro dialysis samples were taken in 15 minutes intervals and noradrenaline (NA) and its metabolite, 3-methoxy 4-hydroxy phenylglycol (MHPG), were measured by HPLC-ECD. Results: The NA and MHPG concentration in the first and second phases of formalin test did not change significantly in neither test nor control groups. Conclusion: LC has no role in perception of pain induced by formalin test during anesthesia.
Narges-Al-Sadat Mojabi, Akram Eidi, Mohammad Kamalinejad, Ali Khoshbaten, Ali Noroozzadeh, Hedayat Sahraei, Farial Khamseh, Farzaneh Zighimat,
Volume 12, Issue 2 (8-2008)
Abstract

Background: Previous studies have confirm the effects of water extract of Crocus sativus on the euphoric and behavioral properties of morphine in mice. Objective: In the present study, the effects of intra-accumbal administration of alcohol extract of Crocus sativus stigma on the acquisition and expression of morphine-induced conditioned place preference (CPP) in male Wistar rats (250-300 g) were investigated. Material and Methods: This experimental study was conducted on the 78 male rats that were divided in 18 groups (n=6/group). In a pilot study, different doses of morphine (0.5, 1, 2.5, 5, 7.5 and 10 mg/kg) were injected to the animals for evaluation of the drug's ability to induction of place preference. In the second phase of the experiments, the extract of the C. sativus (1, 5 and 10 µg/rat), was administered into the nucleus accumbens shell during or after induction of morphine CPP. Then, CPP were tested in the animals. One-way Analysis of Variance (ANOVA) was proformed for statistical procedure. Results: Administration of morphine (0.5, 1, 5, 7.5 and 10 mg/kg), indcreased the time spend in the compartment paired with morphine (i.e. conditioned place preference-CPP). The increament was significant for the dose 10 mg/kg of morphine. Injection of the same doses of the extract (1, 5 and 10 µg/rat) 5 min before morphine (10 mg/kg) administration, caused a decrease in the time spent in drug-paired side in doses 5 and 10 µg/rat of the extract. In addition, injection of the plant extract (1, 5 and 10 µg/rat) in to the shell part of nucleus accumbens in the test day to the animals in which reveived morphine (10 mg/kg) in the conditioning days decreased the expression of morphine CPP in the animals which was statisticaly significant for doses 5 and 10 µg/rat of the extract. Conclusion: It could be concluded that intra-accumbens shell compartment njection of the alcoholic extract of C sativus can inhibit the acquisition and expression of morphine-induced CPP and shift it to the aversive state in rats. .
Masoud Fereidoni, Leila Etemadi,
Volume 12, Issue 2 (8-2008)
Abstract

Introduction: Feverfew (Tanacetum parthenium) (T.p.) is widely used in folk medicine to treat many diseases. We reported the analgesic effect of T.p. flower and leaf previously. Present study is designed to find the mechanism underlying the anti-nociceptive effect of the aqueous extract of T.p. flower. Method: Based on our previous study, the dose 50 mg/kg i.p. of the T.p. aqueous extract had a potent analgesic effect on mice (NMRI) (20 ± 2 g) in formalin test which is used in the present study also. Here, we study the roles of opioidergic, sertoninergic and α - adrenergic systems on the anti-nociceptive effect of the extract. Animals had pretreated with drugs, 15 min before the extract treatments, including opioid antagonist naloxane (5mg/kg, i.p.), sertoninergic antagonist cyproheptadine (4 mg/kg, i.p.) and α-adrenergic antagonist phentolamine (20 mg/kg, i.p.) separately (each group with n≥6). Saline and extract used as controls. Results: In contrast to extract analgesic effect, pretreatment with naloxan increased the pain sensation in the neurogenic phase of formalin test (p<0.001). Pretreatment with cyproheptadine increased the sensation of pain in both early and late phases (p<0.05). Inhibition of α -adrenergic system was not be able to attenuate the anti-nociceptive effect of the extract. Discussion: The involvement of sertoninergic system in anti-nociceptive effect of the T.p. extract is proposed by the results. Also the involvement of opioidergic system has to be mentioned in this effect.
Abbas Haghparast, Amir-Mohammad Alizadeh, Fereshteh Motamedi,
Volume 12, Issue 2 (8-2008)
Abstract

Introduction: Although formalin-induced activity in primary afferent fibers and spinal dorsal ‎horn is well described, the midbrain neural basis underlying each phase of behavior in ‎formalin test has not been clarified. The present study was designed to investigate the nucleus ‎cuneiformis (CnF)‎‏ ‏neuronal responses during two phases after subcutaneous injection of ‎formalin into the hind paw of rat.‎ Materials & Methods: In this study, seventy six male NMRI adult rats, weighing 230-320 g ‎were used. Control group (n=24), which was tested merely for determining spontaneous firing ‎rate of CnF neurons. Saline group (n=15) which received saline (50µl s.c.) instead of ‎formalin into the plantar surface of hind paw after 15 min baseline recording. Formalin group ‎that formalin-induced neural activity of 37 cells simultaneously recorded from the CnF during ‎first phase (0-5 min) and second phase (15-60 min) of formalin test in 5-min intervals, using ‎an extracellular single unit recording technique.‎ Results: The‏ ‏baseline firing rate of neurons in the CnF varied between 1.2 and 39.2 spikes/sec ‎and the average frequency of spontaneous activity over 1 h was 11.8 ± 1.1 spikes/sec. There ‎were three neural clusters after formalin injection. Neurons in cluster 1 (46%) exhibited ‎severe, transient excitatory response in the first (acute) phase while neurons in cluster 2 (35%) ‎exhibited tonic but long-lasting excitatory response in the second (chronic) phase. Cluster 3, a ‎small portion of neurons (about one fifth) which failed to show any evident responses to ‎formalin test. ‎ Conclusion: Our findings suggest that alteration of neural activity and pattern in the ‎spontaneous background of CnF neurons can be mediated a role in the transmission of ‎nociceptive information induced by the peripheral injection of formalin and can be discussed ‎in light of the role of these neurons in nociceptive information processing following ‎peripheral stimuli.‎
Hassan Azhdari Zarmehri, Saead Semnanian, Yaghoub Fathollahi,
Volume 12, Issue 3 (11-2008)
Abstract

Introduction: Orexin-A and B (Hypocretin 1 and 2) are neuropeptides that are mostly expressed in the posterior and lateral hypothalamus (LH). Intracisternal (ICV) and intratechal (IT) injections of orexin-A (hypocretin-1) have been shown to elicit analgesic responses in formalin test. However, the locations of central sites that may mediate these effects have not been clearly elucidated. Orexin-containing fibers are projected to periaqueductal gray matter (PAG), which is involved in pain modulation. Methods: Behavioral study was done on male Sprague Dawley rats (200-300 g) in formalin induced nociceptive behaviour. Results: Intra-PAG microinjection of orexin-A produced a dose-dependent inhibition of formalin-evoked behaviour in interphase and phase 2, but not in phase 1, indicating an antinociceptive role of exogenous orexin-A in the PAG. Analgesic effect of orexin-A was less than and specific to inter- and late phase of formalin test, when compared with that of morphine (5 μg/0.5μl) after intra-PAG administration. Conclusion: The obtained results suggest that orexin-A plays an anti-nociceptive role in PAG, on the interphase and late phase of formalin test in rats. So it is possible that orexin-A might be involved in the mechanisms of inter- and last phases of formalin induced behaviours.
Shiva Nasiraei-Moghadam, Hossein Bahadoran, Saghar Saeidabadi, Jamal Shams, Hedayat Sahraei,
Volume 12, Issue 4 (1-2009)
Abstract

Previous studies have shown that morphine administration could inhibit neural tube development in rat embryos and produce behavioral defects in human and animals. In the present study, the effects of maternal morphine consumption on embryonic neural plate development in Wistar rats were investigated. Methods: Twenty-four female Wistar rats (250-300 g) were crossed with males. After pregnancy, the treatment group received 0.1 mg/ml of morphine in drinking water daily (14 ml water/100 g of body weight for each rat), while the control group received tap water. Eight days and 12 hours after the onset of pregnancy, the animals were anesthetized by chloroform and the embryos were taken out surgically. Lengths of embryos were determined by a Caliper. Embryos were fixed in formalin 10% and tissue was processed, sectioned and stained with H&E. The sections were examined for neural plate development by a light microscope and the MOTIC software. Results: Embryonic length in the treatment group was significantly decreased compared with the control group. Neural plate was observed in the control group. Development of neural plate and other embryonic layers (ectoderm, mesoderm and endoderm) were delayed in the treatment group. The ectoderm layer group was poorly developed in embryos exposed to morphine. Conclusion: Morphine consumption during pregnancy could cause a delay in the development of the neural plate as well as the embryonic layers and especially the ectoderm.
Mahnaz Taherianfard, Mehdi Fazeli, Farzad Saremi, Homan Bozorgi,
Volume 13, Issue 1 (4-2009)
Abstract

Introduction: In female rats sensitivity to antinociceptive treatment varies during estrous cycle stages. The role of GABA through GABAB receptor in nociception has been established. The aim of the present study is to investigate the effect of intercerebroventicular injection of GABAB receptor agonist (baclofen) and GABAB antagonist (CGP35348) on pain sensitivity during different stages of estrous cycle. Methods: Forty adult female rats weighing 200-220g were used. Rats were maintained on 12 h reversed light/dark cycle, and standard temperature 22 ± 2°C. Food and water were available ad libitum. Pain sensitivity was evaluated by formalin test, performing by subcutaneous injection of 50µl formalin solution (2.5%) into the hind paw in each stages of estrous cycle. Data were analyzed by two ways ANOVA measuring and Tucky test as post-hoc test. The level of significance was P<0.05. Results: Our data showed that baclofen significantly decreased pain sensitivity in all stages of estrous cycle (P<0.05). The analgesic effect of baclofen was significantly higher during metestruse and diestruse as compared to proestruse and estrus (P<0.05). CGP35348 significantly increased pain sensitivity in all stages of estrous cycle (P<0.05). The hyperalgesic effect of CGP35348 was significantly lower during metestruse and diestruse than proestruse and estrus (P<0.05). Administration of baclofen in pretreated rats with CGP35348 did not induce any significant change in pain sensitivity (P>0.05). Conclusion: We have demonstrated that GABA through GABAB receptor can modulate pain sensitivity during estrous cycle.
Jamal Shams, Safieh Molavi, Sedigheh Marjani, Mohammad Kamalinejad, Homeira Zardooz, Hedayat Sahraei, Ali Noroozzadeh,
Volume 13, Issue 2 (8-2009)
Abstract

Background: Previous studies have indicated that administration of saffron extract could induced reward and reduces morphine reward as investigated by place preference and behavioral sensitization in male and female mice. In the present study, the effects of water extract of Crocus sativus on the acquisition and expression of tolerance to morphine-induced hyperalgesia in female N-MRI mice (20-25 g) were investigated. Matherila and Methods: Tail Flick technique was implicated in the present study. Morphine tolerance achived by morphine (50 mg/kg twice daily) injections for three consecutive days. On the 4th day of the experiments, morphine tolerance was assesed in animals by injection of effective dose of morphine (10 mg/kg). The extract of the C. sativus was administered during (development of tolerance) or after induction of morphine tolerance (expression). Results: Results showed that administration of morphine (1, 5, 10 and 20 mg/kg), induced a significant analgesia in animals. Administration of the plant extract (1, 2.5, 5, 10, 50 and 100 mg/kg) also produced analgesia which was statistically significant in dose 10 mg/kg of the extract. Injection of the plant extract (1, 2.5 and 5 mg/kg) in the test day, 30 min before morphine (10 mg/kg) reduced the expression of morphine tolerance. Administration of the extract (1, 2.5 and 5 mg/kg) during the induction of morphine tolerance, have not any effect on the development of morphine tolerance . Conclusion: It could be concluded that injection of the extract of C sativus can inhibit the expression but can not altered the acquisition of morphine tolerance. In addition, the extract could induced analgesia by it-self.
Farinaz Nasirinezhad, Ehsan Ramezanian Nick, Mahsa Sadeghi, Mohammad Fereshtenezhad,
Volume 13, Issue 2 (8-2009)
Abstract

Introduction: As sex differences have been observed repeatedly in chronic pain, it is likely that the gonadal hormones are responsible for these differences. To investigate the responsible mechanism for chronic pain different models have been created. This study is examining the effects of gonadal hormones on nociceptive responses of the rats in CCI (chronic constriction injury) and SNI (spread nerve injury) model. Methods: For this reason male rats were undertaken to gonadectomy or sham surgery two weeks before nerve injury. A plantar analgesic meter was used to measure gonadectomy-induced changes in paw withdrawal latency (PWL) values, and von Frey monofilaments and Randal selitto test were used to assess changes in paw withdrawal threshold (PWT) in response to mechanical stimuli. Animals were subjected to the behavioral tests before induction of nerve injury and then once a week starting from the first week after nerve injury for three weeks. t-test and Mann-Whitney were used for statistical analysis. Results: The data revealed that PWL and PWT values were the same in these two nerve injury models and PWL was significantly lower in gonadectomized rats comparing to sham group. There were no gonadetomy-related differences in the development of mechanical allodynia. Also it seems that mechanical hyperalgesia is more affected by sexual hormones in SNI model during the first week after nerve injury. Conclusion: These findings demonstrate that CCI and SNI model induces similar nociceptive behaviors in rats and mechanical and thermal nociceptive responses are differentially affected by gonadal hormones in male rats.
Mojdeh Navidhamidi, Mohammad Javan, Yaghoub Fatholahi, Saeed Semnanian,
Volume 14, Issue 2 (7-2010)
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.
Jamal Ghorbi, Mohammad Javan, Vahid Sheibani, Amir Zarebkohan,
Volume 14, Issue 2 (7-2010)
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.

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