IRANIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Year:2019 | Volume:3 | Issue:1 (9)|Papers Count:8

Background and aims: Neuropathic pain is an unpleasant sensory experience which is caused by damage to the neural cells. Due to the difficulty in treating neuropathic pain, deep insight into the neuropathic pain mechanisms may be promising. Therefore, this study reviews the peripheral mechanisms involved in the pathophysiology of neuropathic pain. Methods: In this study, previous investigations about peripheral mechanisms responsible for neuropathic pain which is cited in the PubMed database from 1999 till 2017 were reviewed. Results: In this review, many of the peripheral mechanisms involved in neuropathic pain were considered. In addition, different receptors and ion channels, synaptic physiology involved in neuropathic pain such as neuronal arborization and also the regulation of pain mediators especially in animal models were studied. Overall, nociceptors sensitization, changing in the ion nociceptors channels expression and frequency, neuronal arborization are the major peripheral mechanisms responsible for neuropathic pain. Conclusion: Due to the difficulty of diagnosing and treating neuropathic pain, pharmacological and nonpharmacological therapies, as well as combined therapies, are very important. Among the pharmacological treatment, using drugs which play as antagonists of receptors and channels involved in the pain process, including topical antipsychotics and opioids and among the non-pharmacological treatment, physiotherapy, spinal cord stimulation, and modern surgical procedures recommended. Also, using the drug with natural sources to inhibit the mentioned mechanisms can be considered.

Background and aims: Alzheimer’ s disease (AD) is characterized by loss of memory and an impairment of multiple cognitive functions. One of the factors that play an effective role in the pathogenesis of Alzheimer’ s disease and memory impairment is oxidative stress. Ascorbic acid has high antioxidant activity and is involved in memory and learning. In this study we assessed the impact of ascorbic acid on the memory improvement in an animal model of Alzheimer’ s disease induced by streptozotocin in rats. Methods: Streptozotocin was injected into cerebral lateral ventricles of rats bilaterally. After two weeks, ascorbic acid (5mg/kg) was microinjected into brain lateral ventricles for five days. The Morris water maze test was then performed to examine spatial memory of rats. At the end of behavioral test, hippocampal antioxidant activity was measured. Results: Streptozotocin significantly impaired spatial memory of rats compared to control group (p < 0. 001). The level of oxidative stress significantly increased by streptozotocin compared to control group (p < 0. 001). Ascorbic acid improved spatial memory and decreased the level of oxidative stress in streptozotocin-received rats (p < 0. 001). Conclusion: It seems that ascorbic acid improves memory impairment of streptozotocin-received rats by diminishing the oxidative stress.

Background and aims: Neuropathy as a common complication of diabetes might be induced by changes in the extracellular matrix, including the thickening of the basal membrane of the peripheral nerve and elevation of the advanced glycation end products in the extracellular matrix. Benfotiamine inhibits nerve damages induced by hyperglycemia through several pathways. The purpose of this study was to study the effect of Benfotiamine administration on the tensile strength of the sciatic nerve and its acellular scaffold in diabetic rat model. Methods: Sixty rats were divided into control, sham and 4 and 8 weeks diabetic groups (with and/or without benfotiamine oral treatment; 100 mg /kg). Diabetes was induced by intraperitoneal injection of streptozotocin. At the end of the experimental periods (4 and 8 weeks) 1 cm segment of the middle part of the sciatic nerve was removed, half of it was decellularized by the Sandal method and then subjected to tensile strength test. Thin and semi-thin sections were also prepared for histological examinations. Results: The mean force for the breaking of nerve segment in the diabetic groups was significantly reduced compared to control group. Also, the length increase up to the breaking point in diabetic groups was significantly shorter than control group. There were no significant differences in the length increase and maximum force in benfotiamine-treated diabetic groups compared to control group Conclusion: Alteration of extracellular matrix in diabetes condition, might affect the structure of the collagen fibers and therefore reduce the strength of the nerve against the stretch.

Background and aims: In traditional medicine, some plants can relieve pain. Scrophularia striata is traditionally used among people living in Zagros area for its analgesic effects. In this study, anti-inflammatory and analgesic effects of hydroalcoholic extract of Scrophularia striata seeds are investigated. Methods: Eighty-four adult male NMRI mice were used. Xylene-induced ear edema test was used to evaluate antiinflammatory activity and formalin test was used to evaluate anti-nociceptive activity. In each of these two tests, the animals were divided into 6 groups (n = 7) including control, positive control (receiving dexamethasone in inflammatory test, and morphine in formalin test), and experimental groups receiving hydroalcoholic extract of Scrophularia striata seeds at doses of 30, 60, 90, and 120 mg/kg. Injections were performed intraperitoneally. Results: The results showed that the extract significantly (p < 0. 05) reduced inflammation at doses of 30, 90 and 120 mg/kg. Furthermore, the extract decreased acute phase of the pain by the dose of 120 mg/kg (p < 0. 05), the peripheral phase by the doses of 60 (p < 0. 05), 90 (p < 0. 001), and 120 (p < 0. 001) mg/kg, and the chronic phase by the doses of 90 (p < 0. 001) and 120 (p < 0. 001) mg/kg. Conclusion: This study showed that hydroalcoholic extract of Scrophularia striata seed has anti-inflammatory and antinociceptive effects in the animal model.

Background and aims: Here we aimed to comprise several histological methods to determine the most accurate technique for evaluation of efficacy of neuroprotective agents in animal model of multiple sclerosis (MS). Methods: Male C57BL/6 mice were treated for 6 weeks in control, control + Benzoraic acid (BA, as neuroprotective agent) 20, 40, 80 mg/kg during last 2 weeks, Cuprizone (0. 2%) as demyelinating agent, and Cuprizone (0. 2%) + BA (20, 40, 80 mg/kg during last 2 weeks) groups. At the end of experiment, histological examinations including immunohistochemistry (IHC), Hematoxylin & Eosin (H & E) staining, Luxol Fast Blue (LFB) staining, and Transmission Electron Microscopy (TEM) techniques were performed for evaluation of myelin damages. Results: Significant myelin damage was detected by all of the used histological methods in Cuprizone group (p < 0. 001 compared to control group). LFB technique could not show improvement in damages by all doses of BA. The H & E, IHC and TEM methods showed significant protective effects of the high BA dose compared to Cuprizone group. Only the TEM method could show significant (p < 0. 05) protective effect of the medium BA dose. Conclusion: TEM was the most and LFB was least sensitive methods. Present study suggests simultaneous using of methods such as H & E for better assessment of neuroinflammation and IHC for confirmation of TEM results. Moreover, in the case of restriction in methods, TEM and IHC are the most sensitive methods and could provide reliable results related to efficacy of neuroprotective agents in this model.

Background and aims: This study investigated the effect of combination therapy with vildagliptin and ischemic post-conditioning (IPostC) on myocardial infarction and expression of micro ribonucleic acid miR-140 and miR-125b as the regulators of mitochondrial dynamics in myocardial ischemic-reperfusion (IR) injury of rats with type 2 diabetes mellitus. Methods: Chronic diabetes was induced in rats using a high-fat diet protocol and a low dose of streptozotocin over a period of 3 months. In the last month of the diabetic period, vildagliptin was administered orally for 4 weeks once a day, and IR injury was induced by closing the anterior left coronary artery bypass graft for 35 min followed by reopening of it for 60 min. The IPostC protocol was performed at the onset of reperfusion in 6 alternative cycles of 10-second ischemia and reperfusion. At the end of the experiment, the ischemic region of left ventricles was sampled. The size of the risk area and myocardial infarction were studied by planimetry. The levels of miR-140 and miR-125b expression in the left ventricle were evaluated using real-time PCR. Results: The combination of vildagliptin and IPostC was able to reduce myocardial infarction compared to untreated diabetic group (p < 0. 05), inhibit the elevated expression of miR-140 caused by IR damage, and increase the expression of miR-125b in diabetic hearts (p < 0. 05). Conclusion: The combination of vildagliptin and IPostC has cardioprotective effect against IR injury in rats with type II diabetes by change in the expression of micro-RNAs involved in cardioprotection.

Background and aims: Inflammatory pathways play an important role in incidence and progression of Parkinson’ s disease (PD). Ghrelin has anti-inflammatory and antioxidant effects and inhibits the release of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α ). This study has aimed to investigate the effect of ghrelin hormone on amount of TNF-α , and gene expression of cytochrome b and interleukin10 in Parkinson’ s disease induced by1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in male mice. Methods: Thirty male NMRI mice were randomly divided to 5 groups (six mice in each) including control, saline, ghrelin hormone, Parkinson, and Parkinson + ghrelin hormone. Parkinson’ s disease was induced by intraperitoneal (i. p. ) injection of 25mg/kg MPTP for 4 days. Ghrelin was injected for 28 days (0. 4μ g/kg, i. p. ). Catalepsy was evaluated by bar test at the 1st, 7th, 14th, 21th, and 28th day after injection of MPTP. TNF-α level and gene expression of cytochrome b, and interleukin10 were measured in Substantia nigra and Corpus striatum by ELISA and Real time PCR techniques at the 29th day. Results: Catalepsy and TNF-α level significantly increased in substantia nigra and corpus striatum of the Parkinson group, whereas gene expression of cytochrome b, and interleukin10 decreased (p < 0. 001). On the other hand, ghrelin hormone significantly decreased catalepsy and TNF-α level while increased gene expression of cytochrome b, and interleukin10 (p < 0. 001). Conclusion: It seems that ghrelin hormone improves catalepsy, decreases TNF-α level, and increases gene expression of cytochrome b, and interleukin10 by inhibiting inflammatory pathways involved in PD.

Gallium citrate radiopharmaceutical is used in nuclear medicine imaging to detect soft tissue tumors and inflammatory diseases. The aim of this study was to investigate changes in parathormone and thyroid stimulating hormones following radiotherapy with gallium citrate. Sixty male rats were assigned randomly to two groups. The first group was considered as control and the second group received 0. 03 mCi of gallium citrate by intraperitoneal injection. After 4h hours, blood sample was taken from their heart and the parameters were measured. Data were analyzed by independent sample t-test. The results showed a significant increase in parathyroid hormone, and a significant decrease in thyroid stimulating hormone serum levels of rats treated by gallium citrate.