hossein ali safakhah

Peripheral neuropathy (PN) is resulted from damage to the peripheral nervous system (PNS) and usually causes weakness, numbness, and neuropathic pain, which is a type of chronic pain. Despite the variety of treatment options, treating neuropathic pain faces challenges and the existing treatments are not yet satisfactory. Nervous steroids show important physiological regulators of PNS function. Progesterone is a neurosteroid that has both analgesic and anti-inflammatory properties. Also, GABA-A receptors play an important role in mediating the effect of progesterone. This study was designed to determine whether progesterone can prevent electrophysiological deterioration of the sciatic nerve in the chronic constriction injury (CCI) model of neuropathic pain in rats and that do this effect through GABA-A receptors.

In this study, 140 male Wistar rats in 14 groups (n=10) were used. Neuropathic pain was created by the CCI method in the relevant groups. After CCI induction, progesterone and bicuculline or their vehicles were administered daily until day 13 post-CCI. After that, nerve conduction velocity (NCV) tests were performed according to Julu methods on days 14 and 27 after CCI.

According to the findings of this study, daily injections of progesterone for 12 days before complete neuropathic pain evolution in CCI rats could prevent significantly the reduction of sensory and motor nerve conduction velocities compared to the CCI group on days 14 and 27 after CCI. Furthermore, this effect of progesterone was blocked by bicuculline administration

The findings of this study showed that before complete neuropathic pain evolution, chronic progesterone administration may prevent electrophysiological disorders of the sciatic nerve (at least to some extent through GABA-A receptors) in CCI-induced peripheral neuropathy and these effects continue in the accepted range time of the CCI mode.

Neuropathic pain intensifies the response to painful and non-painful stimuli. Curcumin is one of the substances that have analgesic and anti-inflammatory properties. Also, exercise as a behavioral and non-pharmacological method has beneficial effects on general health under many neuropathic diseases. Also, the combined effect of these two factors on peripheral nerve conduction velocity of the sciatic nerve in patients and animals has been less studied. So, we suggested the study of the preventive effects of combined curcumin and exercise on electrophysiological parameters of the sciatic nerve in the neuropathic pain model of chronic sciatic nerve compression in rats.

80 Male Wistar rats were randomly allocated to 8 groups (n=10). First, neuropathic pain was induced by the chronic constriction injury (CCI) method in the respective groups. To prevent neuropathic pain, two weeks before surgery, forced exercise was started in the exercise group, and after a 5-day recovery period, was performed again for one week until the 14th day of the experiment. After CCI surgery, 60mg/kg curcumin or its vehicle injection was performed in the curcumin and vehicle groups until day 14, and electrophysiological tests of the sural and tibial nerve were performed on day 15.

The results showed that before stabilizing neuropathic pain on day 14 of the experiment, co-administration of curcumin and forced exercise could prevent sural and tibial nerve conduction velocity (SNCV and MNCV) loss compared to the CCI group.

The findings of this study suggest that co-administration of curcumin and forced exercise may prevent electrophysiological disorders of the sciatic nerve, before the complete stabilizing of peripheral neuropathy.

Neuropathic pain is a chronic pain that results from damage to the central and peripheral nerves. According to the previous studies, curcumin and exercise can be effective treatments for alleviating sensory neuropathic pain individually. Now the combined effect of chronic curcumin (Cur) and forced exercise on behavioral pain responses in the neuropathic pain model of chronic constriction injury (CCI) in rats is considered.

80 Male Wistar rats were randomly allocated to eight groups (n=10). These groups include Sham+ Vehicle (Veh), Sham+Exercise, CCI+Veh, CCI+Exercise, CCI+Veh+Exercise, Cur+CCI, Exercise+Cur+CCI. First, neuropathic pain was induced by CCI in the respective groups. For the treatment of neuropathic pain in the Cur+CCI group, animals received curcumin (60 mg/kg) started 12 days after the surgery until day 26. The exercise started 12 days after surgery until day 33 in the CCI+Veh+Exercise and CCI+Exercise groups. Thermal hyperalgesia and mechanical allodynia were performed on days 12 and 34.

We found that CCI-induced neuropathy could produce thermal hyperalgesia and mechanical allodynia 12 days after CCI induction. In addition, co-administration of curcumin and moderate-intensity exercise in each of the treated groups individually could alleviate neuropathic pain compared with the nontreated CCI.

Our findings showed that co-administration of curcumin and exercise individually, could alleviate neuropathic pain compared with nontreated CCI. In addition, there was not any additive or synergistic effect between the treatment of exercise and curcumin.

Peripheral nerve damage is a clinical problem that causes sensory and motor disabilities. Sesamol is an antioxidant that can be effective in repairing various organs. The aim of this study was to evaluate the effect of different doses of sesamol on inflammation and pain in the damaged rat sciatic nerve.

In this study, 35 adult male Wistar rats were used. The rats were randomly divided into five groups: The sham group without crush injury, the control group and three experimental groups respectively received DMSO (solvent) and doses of 50, 100, or 200 mg/kg sesamol intraperitoneally for 28 days after sciatic nerve injury. Then behavioral pain tests including mechanical allodynia and thermal hyperalgesia as well as inflammatory factors including interleukins 6 and 10 in the sciatic nerve were evaluated.

The results showed that administration of 50 and 100 mg/kg of sesamol significantly decreased expression of interleukin 6, and increased expression of interleukin 10, the retraction threshold in the mechanical allodynia test and the response time to thermal pain in the thermal hyperalgesia test in the damaged sciatic nerve than the control group (P<0.05). While administration of 200 mg/kg sesamol had no significant effect.

Administration of 50 and 100 mg/kg sesamol may reduce inflammation and pain in the rat damaged sciatic nerve which may help improve the nerve repair process.

Neuropathic pain is a chronic pain that results from damage to the central and peripheral nerves. According to the previous studies, physical activity or progesterone can be an effective treatment for alleviating sensory neuropathic pain individually. In this way, the combined effect of chronic progesterone and forced exercise on behavioral pain responses in the neuropathic pain model of chronic constriction injury in rats was considered.

Eighty male Wistar rats were used in 8 groups (n=10). First, neuropathic pain was induced by CCI in the respective groups. For the treatment of neuropathic pain, animals in the groups received progesterone (6 mg/kg) started 12 days after the operation until day 26. In exercise groups, the exercise started 12 days after surgery until day 33. Behavioral tests were performed on days 12 and 33.

Interestingly, we found that CCI-induced neuropathy could produce thermal hyperalgesia and mechanical allodynia in experimental groups on day 12 before exercise and progesterone therapy. After the stabilization of neuropathic pain, co-administration of progesterone (6 mg/kg) for 14 days and moderate intensity exercise for 3 weeks in the respective group could alleviate neuropathic pain compared with the CCI and each of treated groups individually.

The findings of this study showed that co-administration of chronic progesterone and forced exercise after the stabilization of neuropathic pain may alleviate neuropathic pain

Neuropathic pain has no definitive treatment and the socio-economic status and personality of patient is severely affected. Since the exercise and/or progesterone effect on Chronic Constriction injury (CCI) neuropathic pain has been studied and each individually have been able to improve neuropathic pain and as a part of its etiology is related to TNF-α production, we tried to test these factors on TNF-α production and electrophysiologic responses of sciatic nerve in neuropathic pain model in rat.

50 male Wistar rats were used in 5 groups. Experimental groups were including: 1- Sham,   2- CCI + Vehicle (VEH), 3- CCI + VEH + Exercise,   4- CCI + Progestrone and 5- CCI + Progestrtone + Exercise. The sciatic nerve CCI model of rat was used to induce chronic neuropathic pain in the respective groups. Some groups of animals treated by progesterone injections (6 mg/kg) or its vehicle from day 1 to day 12 after surgery. The exercise was started two weeks before surgery and again, one-week after that and lasted to day 12. Electrophysiological tests and blood sampling were done on day 13.

The results showed that co administration of progesterone for 12 days and moderate intensity exercise for 3 weeks before complete neuropathic pain evolution could prevent significantly TNF-α production and electrophysiologic (Tibial and sural nerve conduction velocity) abnormality compared to the CCI group as well as compared to the exercise or progesterone group alone.

The findings of this study showed that co-administration of progesterone and forced exercise before neuropathy development may prevent TNF-α production and neuropathic disease. Also, the results showed that the effects of co-administration of progesterone and forced exercise in preventing electrophysiologic abnormality may be additive.

There are various animal models to investigate neuropathic pain which the most usual one is chronic constriction injury method. The aim of the present study was the evaluation of neuropathic pain following chronic spiral suturing around the sciatic nerve without ligation as a new model.

Thirty Wistar male rats, weighting 180-220 gram randomly were divided into three groups as sham, chronic constriction injury (CCI), and chronic sciatic spiral suturing (CSS). CCI was performed by four loos ligation using catgut chromic suture around sciatic nerve. CSS was performed through spirally suturing of catgut chromic four times around the sciatic nerve without any ligation. In the sham group, muscle and skin were sutured after exposing the nerve. To determine mechanical allodynia and thermal hyperalgesia, Von Frey filaments and plantar test devise were used respectively every four days during three weeks.

CCI led to significant mechanical allodynia (P<0.01) and thermal hyperalgesia (P<0.001) compared to sham group. On the other side CSS led to a transient mechanical allodynia (P<0.05) but permanent thermal hyperalgesia (P<0.001) in comparison with sham group. Considerably, the mechanical allodynia in the CCI group was reduced significantly (P<0.01) against that in CSS group, however thermal hyperalgesia were the same in both of CCI and CSS groups.

Chronic spiral suturing around the sciatic nerve without ligation led to thermal hyperalgesia as chronic constriction injury method, but unlike CCI method, led to a temporary mechanical allodynia.

Neuritis is one of the causes of neuropathic pains. It is proved that turmeric and curcumin have anti-neuritis effect that may be reduce of neuropathic pain.

In this study, effects of turmeric and curcumin have been evaluated on behavioral response resulted from chronic constriction injury (CCI) in rat.

In this experimental study Wistar male rat (200-250 gr) were used. For create of CCI, Bennet and Xie (1988) method has been used. 2 weeks after neuritis occurrence, turmeric 60 mg/kg and curcumin 30 and 60 mg/kg injection have been begun and continued until 26th day as daily and Intraperitonealy. Animal behavioral responses have been measured by using of mechanical allodynia (Von Frey) test and thermal hyperalgesia test during 14, 17, 20, 23, 26 and 40 days after neuritis occurrence.

Results indicated that creation of CCI increases behavioral responses as significant. Curcumin injection with dosage of 30 mg/Kg leads to decrease of mechanical allodynia from 20th and thermal hyperalgesia from 23th day. This effect has been observed until 40th day. Curcumin injection with dosage of 60 mg/Kg leads to decrease of mechanical allodynia and thermal hyperalgesia in 26th day. Turmeric injection with dosage of 60 mg/kg had no effect on mechanical allodynia and thermal hyperalgesia.

Finding shown that curcumin has positive effect on decrease of neuropathic pain that induced by CCI. Previous study suggested that the effect of curcumin is partly attributed to attenuation of lipid peroxidation in the periphery that finally reduced of inflammation.

Neuropathic pain is a chronic pain that results from damage to the central nervous system and also environment. Neuropathic pain is important for general health and approximately 6% of the adult population is affected worldwide. Despite the therapeutic choices, treatment for neuropathic pain is facing challenges. An experimental model that is very close to human neuropathic model is the chronic constriction injury (CCI) model. Progesterone (PROG) is one of the most potent anti-inflammatory and anti-inflammatory neurostimulants, and GABA-A receptor palys an important role in mediating the biological effects of PROG. In this study, the effects of PROG on behavioral responses of pain in the neuropathic pain model of CCI, and the possible role of GABA-A receptor in its effect were investigated in rats. 70 male Wistar rats were used in 7 groups (n = 10). First, neuropathic pain was induced by the CCI method in the respective groups. Following CCI, PROG (6 mg/kg) and or the GABA-A receptor antagonist bicuculin (0.5 or 2 mg/kg) or vehicle were administered daily until day 13 post-CCI. On days 14 and 27, the behavioural tests including mechanical allodynia and thermal hyperalgesia were done. Daily injections of PROG PROG for 12 days prevented the mechanical allodynia and thermal hyperalgesia following CCI and this effect was blocked the bicuculin pretreatment. The findings of this study showed that treatment with progesterone may prevent the development of peripheral neuropathy, at least in part, via GABA-A receptors.

Occurrence fatigue during exhaustive exercise occurs in response to lactate accumulation in blood and active muscles. This study aimed to determine the effects of whole body vibration with different speeds on blood lactate during the recovery phase after exhaustive exercise.
Sixty trained young males were randomly assigned to 4 groups and performed 15 min vibration with different speeds namely control (non-vibration), mild vibration (10 Hz), moderate vibration (20 Hz) and severe vibration (30 Hz) immediately after Cunningham exhaustive exercise test. Blood lactate concentrations were measured before, immediately and 15 min after exercise test for all 4 groups.
A significant increase was found in blood lactate immediately after exercise compared with baseline for all groups (p0.05). A significant decrease was observed in blood lactate after 15 min recovery in moderate vibration compared with other groups (p Based on these data, it is concluded that whole body vibration can be affects disposal blood lactate during recovery phase after exhaustive exercise and moderate frequency vibration (20 Hz) is the most effective method.

Studies show that ethanol can induce changes in proteomic profile of human fibroblast cells. Some of these proteins are important in promoting cancer. Thus, analyzing function and interaction networks of these proteins are essential for better understanding the carcinogenesis mechanism of ethanol.
In this study the protein-protein interaction network (PPI) of six significant down-regulated proteins in human fibroblast cells (HFFF2) treated with ethanol were analyzed by using Cytoscape software and its algorithms.
PPI network analysis showed that the constructed network consisted of 756 nodes and 1166 edges. Results indicated that Heterogeneous nuclear ribonucleoprotein A1 with degree = 528 and Betweenness Centrality = 0.74 is a hub protein that ethanol can alter its expression. In addition, module evaluation showed that the hub protein has a key role in different overlapped complexes. On the other hand, annotation studies by using DAVID program indicated that this protein is involved in different important biological processes in the cell.
The six down-regulated proteins treated with ethanol may become carcinogenic and can impose vast alterations in other vital biological processes of the cell. Among them, Heterogeneous nuclear ribonucleoprotein A1 is the most important one

This study was designed to investigate the therapeutic effects of saffron (Crocus Sativus L) and its main constituent crocin on neuropathic pain behavioral responses induced by chronic constriction injury (CCI) in rats. Adult male Wistar rats (200 to 250 g) were randomly assigned into 5 groups: Sham saline, CCI saline, CCI saffron (30 mg/kg), CCI 犺ᲊ (15 mg/kg) and CCI crocin (30 mg/kg). CCI was induced by applying 4 loose ligatures around the sciatic nerve. Two weeks after nerve lesion, injections of saline, saffron or crocin were started and continued until 26th day post-surgery. Pain behavioral responses including mechanical allodynia (von Frey filament testing) and thermal hyperalgesia were measured in 14, 17, 20, 23, 26, and 40th days after CCI. CCI significantly increased pain behavioral responses. Saffron and crocin (30 mg/kg) decreased thermal hyperalgesia and mechanical allodynia on day 26, and this effect continued until the day 40. Crocin at lower dose (15 mg/kg) was ineffective. These findings indicate that treatment of saffron and crocin after CCI may have a therapeutic effect against neuropathic pain, suggesting that these substances may offer new strategies for the treatment of this highly debilitating condition.

Metabolomics is a powerful technique for determination of biomarkers. Here, we aimed to determine discriminatory metabolomic profiles in different stages of sulfur mustard-exposed patients (SMEPs).
Nuclear magnetic resonance spectroscopy was used to analyze serum samples from 17 SMEPs (normal group patients) and 17 SMEPs (severe group patients). Multivariate statistical analysis using random forest (RF) was performed on a ‘training set’ (70% of the total sample) in order to produce a discriminatory model classifying two groups of patients, and the model tested in the remaining subjects.
A classification model was derived using data from the training set with an area under the receiver operating curve (AUC) of 0.87. In the test set (the remaining 30% of subjects), the AUC was 0.8, thus RF model had good predictive power. We observed significant changes in lipid, amino acids and energy metabolism between two groups of patients.
Nuclear magnetic resonance spectroscopy of serum successfully differentiates two groups of patients exposed to sulfur mustard. This technique has the potential to provide novel diagnostics and identify novel pathophysiological mechanisms, biomarkers and therapeutic targets.

Central and peripheral nerve injuries may lead to chronic neuropathic pain in addition to immobility in many injured persons. Exercise as a non-medical procedure has beneficial effects on the well being of individuals in normal and diseased state. Therefore, in the current study we aimed to measure the alleviating effect of physical exercise on neuropathic pain. Male wistar rats weighting 200±20 gram were divided into 5 groups: Intact, sham, neuropathic, exercise before neuropathy, and exercise after neuropathy. After anesthesia, rats underwent chronic constriction injury (CCI) procedure to induce neuropathic injury on the left sciatic nerve. After surgery animals were transferred to individual cages and covered with a towel to prevent hypothermia until regaining consciousness. Mechanical allodynia and thermal hyperalgesia were detected using von Frey Filament and Plantar test, respectively. Mechanical and thermal withdrawal response thresholds were reduced significantly (P<0.05) in the CCI group than sham and intact groups. On the other hand, there was a significant increase in the mechanical (P<0.01) and thermal (P<0.05) allodynia withdrawal response thresholds in post neuropathic exercise groups than the CCI group. Physical activity following certain models of neuropathic pain may lead to significant reduction in mechanical and thermal allonynia

Kojic acid with the chemical structure of 5-hydroxy-2-hydroxymethyl-ˠ-Piron is an organic acid that is biologically produced through aerobic fermentation process by using various substrates and via the function of variety of fungi. This study was aimed to study the optimization of Kojic acid production by Locally Isolated Fungi Aspergillus sp., using ‘Response Surface Methodology’. Kojic acid was produced by fermentation of isolated strain of genus Aspergillus in submerged culture medium. Initial investigation in Kojic acid production process was performed via Plackett-Burman method and by using different nitrogen sources such as yeast extract, peptone, ammonium sulfate, ammonium chloride, urea as well as different carbon sources, including fructose, sucrose, glucose, lactose and maltose. Based on our study, peptone and glucose were the most effective factors with carbon and nitrogen sources in production of kojic acid (P <0.05). The next step was production of 34.4g/L kojic acid by optimizing the effect of environmental factors such as temperature, pH, glucose and peptones, such as carbon and nitrogen sources, used in production of kojic acid and by employing ‘Response Surface Methodology’. Based on the results of this study, the maximum production of kojic acid can be achieved by using glucose (% 8.71), peptone (37.4%), temperature (29.9 ° C) and adjusting pH to 6.75 in the production process.

Gastric acid secretion is one of the most important causes of peptic ulcer. Dopamine and its agonists have a protective role in the stomach. In the present study the role of α1 and β adrenoceptors and dopamine D2 receptors in the effects of bromocriptine on histamine-induced gastric acid secretion were evaluated. 93 Male Wistar rats weighing between 180-220 g were used. After the induction of anesthesia with ketamine/xylazine, for histamine infusion and tracheostomy, jugular vein and trachea were exposed respectively. For injecting physiologic saline and removing gastric secretion a polyethylene tube and a cannula was inserted into the stomach through esophagus and pyloroduodenal junction respectively. Every 10 minute 2 milliliter Physiologic saline was introduced and removed through esophagial and pyloro duodenal tube respectively during 2 hour period of experiment. pH of removed solution was detected, using 0.1 N NaOH was titrated and then acid content was reported as µEq/10 minute. Gastric acid secretion was increased significantly 30 minute after histamine (0.8 mg/100g/h) infusion and remained high throughout experimental period. Administration of bromocriptine as a dopamine D2 receptor agonist (8 mg/kg) before histamine infusion significantly decreased stimulated gastric acid secretion. Domperidone (peripheral D2 receptor antagonist) and or propranolol (β adrenoceptor antagonist) injection before bromocriptine prominently augmented effect of bromocriptine on histamine-stimulated gastric acid secretion. It is possible that effect of bromocriptine on histamine-stimulated gastric acid secretion does not mediated via D2 dopaminergic and β adrenergic receptors

Neuropathic pain syndromes are changes resulted from damage to neuronal pathways which is characterized by spontaneous burning pain with accompanying allodynia and hyperalgesia. The mechanisms underlying neuropathic pain are poorly understood. The present study explores behavioral characteristics of the neuropathic pain models chronic constriction injury (CCI) and spared nerve injury (SNI). Experiments were performed on four groups (n= 8) of male Sprague-Dawley rats (230-280 g). Anesthesia was initially induced with sodium pentobarbital (i.p.) at a dose of 50 mg/kg. The CCI model was made by loose ligation of the sciatic nerve. Also a lesion of two of three terminal branches of the sciatic nerve leads to a SNI model. The animals were tested for behavioral responses cold-and mechano-allodynia and heat-and mechano-hyperalgesia. The cold and mechanical stimulations in the cold- and mechano-allodynia phenomena were applied through acetone and von Frey filament respectively. Pin-prick and radiant heat were applied as thermal and mechanical stimulations in the heat- and mechano-hyperalgesia respectively. Behavioral tests were conducted on the animals prior to surgery (the day 0), and 3, 7, 14, 21 and 28 days post-operation. Our results indicate that, in comparison to the controlled group, the rats in both SNI and CCI groups reveal an obvious difference in behavioral responses. Although the SNI, compared to the CCI group were more sensitive to mechano-allodynia shortly after surgery (p<0.5) however, both groups share a similar pattern of behavior. In the heat-hyperalgesia testing, again, the animals in the CCI and SNI groups behaved differently than those in the controlled group, but no variation was evident among the test groups, themselves. These findings clearly show that the two neuropathic models produce abnormal pain-related disorders in the rats. A major feature of the SNI model was the very marked hypersensitivity to normally innocuous mechanical stimuli.