Physiology and Pharmacology
Year:2003 | Volume:7 | Issue:1|Papers Count:13

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 III 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.

The effect of ketamine (1-100 µM), which has NMDA receptor antagonist properties, on synaptic transmission and long-term potentiation (LTP) in CA, area of rat hippocampus was examined in vitro. Field potentials were recorded in pyramidal cell layer following Schaffer collateral stimulation. Primed-burst stimulation (PBs) was used for induction of long- term potentiation. The amplitude of population spiks (PS) was used as a measure of LTP induction. The results showed that ketamine (1-100 µM) affected baseline synaptic transmission in a concentration-dependent pattern. Furthermore, ketamine application at a high concentration (50-100 µM) for a period of 20-30 min markedly blocked the induction of LTP, whereas lower concentrations of ketamine (1-10 µM) failed to block LTP. However, ketamine at a concentration of 20 µM affected NMDA-mediated LIP induction in a different pattern. It is concluded that the effect of ketamine on baseline synaptic transmission and LTP induced by a 100 Hz PBs depends on ketamine concentration.

It has been shown that L-arginine like the abused drugs could release dopamine from mesa-corrico-limbic system. The purpose of the present study was to compare the effect of L-arginine with morphine as a standard abuse drug in induction of conditioned place preference (CPP) in rat. For this purpose, male Wistar rats (250-300 g) were used in the experiment. Five days after surgical cannulation in the ventral tegmental area (VTA), different doses of L-arginine, L-NAME or morphine were injected and conditioned biased method was preformed. The results showed that: 1. Intraperitoneal (i.p.) (0.1, 1 and 5 mg/kg) but not intra VTA (i-VTA) (0.3, 0.1 and 3 µg/rat) injections of L-arginine induced CPP in a dosedependent manner. Injection of 10 mg/kg (i.p.) and 2 µg/rat of morphine (i-VTA) also caused a significant CPP in rats. Both i.p. (0.1, 1 and 5 mg/kg) and i-VIA (0.3, 0.1 and 3 µg/rat) injection of L-NAME did not produce any effect in the rats, but the drug at a higher dose (5 mg/kg, i.p.) attenuates the CPP induced by L-arginine (5 mg/kg, i.p.). Administration of morphine (l0 mg/kg, i.p.) on three consecutive days and, then with av 3-day interval caused the occurrence of sensitization to morphine, so that injection of , ineffective dose of morphine (0.5 mg/kg, i.p.) induced CPP in sensitized rats. However, I when the procedure was repeated for L-arginine (5 mg/kg, i.p.), rats showed negative I response to the ineffective dose of L-arginine (0.1 mg/kg, i.p.). Meanwhile, in rats I which received L-arginine (5 mg/kg, i.p.) on training days, injection of the same dose of I L-arginine on "the test day dramatically decreased the time spent in drug-paired side, while injection of morphine (10 mg/kg, i.p.) on the test day to those rats which have received morphine (10 mg/kg, i.p.) on training days caused an increase in time spent in the drug-paired compartment. It could be concluded that i.p. injection of L-arginine causes significant CPP in rats and this behavior is attenuated by nitric oxide synthase inhibitor, L-NAME. Furthermore, the site of action of the drug seems not to be VTA. On the other hand, behaviors due to administration of L-arginine did not show some properties of abused drugs such as sensitization and state dependency.

There are some evidence regarding anti-allergic and anti-inflammatory effects of licorice common in traditional medicine and its usefulness in diabetes mellitus and diabetes insipidus and its stimulatory effect on ademocortical gland. This medicinal plant contains glycyrrhizin, sterogenic substances, cumarins, flavonoids, sterols, choline, sparagine and glaberin. Glycyrrhizin and glaberin have analgesic and antiinflammatory effects. In this study, we evaluated the effect of licorice root extract on acute carrageenan-induced inflammation in the rat's hind paw as compared to antiinflammatory effect of iboprofen. For this purpose, adult male rats were divided into eight groups. Paw edema was induced by intraplantar injection of 0.1 ml of 0.5% carrageenan solution. Different doses of licorice root extract (50, 100, 200, 300 mg/kg, i.p.) and ibuprofen (12 mg/kg, i.p.) were given ten minutes before injection of carrageenan. Assessment of edema was performed by evaluation of volume change as determined by plethysmometry and extravasation of Evans blue dye as measured by spectrophotometry and changes in paw weight in test groups as compared to the control group. The results showed that the extract exerts a significant inhibitory effect on hind paw edema (volume) in a dose-dependent manner. In this respect, the maximum inhibition (54%) was achieved at a dose of 300 mg/kg of the extract and this dose was comparable to ibuprofen at a dose of 12 mg/kg. Meanwhile, the extract administration significantly reduced Evans blue content (100,200 and 300 mg/kg) as compared to the control group. It could be concluded that licorice root extract is able to inhibit acute inflammatory response in the rat hind paw, and these effects are comparable to ibuprofen.

Dextromethorphan is a NMDA receptor antagonist in the glutamatergic system. Currently, there are some reports showing that the glutamatergic NMDA receptor mechanism stimulates dopamine release from several brain regions. This effect may in part modulate the stereotyped behaviors of dopaminergic system. The purpose of the present study was to determine the interaction between the blockade of NMDA receptor and the stereotyped pecking behavior in chicks. Dextromethorphan was used for the blockade of NMDA receptors. In the present study, the effects of dextromethorphan and different dopamine receptor antagonists on apomorphine-induced pecking behavior were examined. For the induction of pecking, apomorphine (ED53) at a dose of 0.5 mg/kg (s.c.) was used. The results showed that dextromethorphan (5-15 mg/kg, s.c.) in a dose-dependent pattern reduce the pecking behavior. Subcutaneous injection of dextromethorphan (5 mg/kg, EDso) did not alter the suppressive action of the dopamine DJ receptor antagonist SCH 23390 (1-4 mg/kg, s.c.), but potentiated the suppressive action of the dopamine Dz receptor antagonist sulpiride (10-30 mg/kg, s.c.). The peripheral dopamine receptor antagonist domperidone (5 and 10 mg/kg, s.c.) elicited no significant effect. These results suggested that the central dopamine Dl receptor mechanism in part mediates the suppressive action of dextromethorphan on apomorphine-induced pecking behavior.

Human recombinant erythropoietin is a synthetic hormone for treatment of some kinds of anemia. In this study, the effect of this hormone was investigated on blood cell changes in adult and immature rats. For this purpose, the hormone was administered at doses of 50, 100, and 200 IU/Kg (s.c.) twice a week for a period of 6 weeks. Then, the number of red blood cells (RBC), subtypes of white blood cells (WBC), and platelets were counted using HI counter. For statistical analysis, ANOVA (followed by Tukey post-hoc test) and paired student's t-test were used. The results showed that the number of RBC increases by 15% as the dose of the hormone increases in both groups of rats. In addition, number of WBC decreased by 10% at doses of 50 and 100 IU/Kg of the hormone. There was also a decrease in the number of neutrophils (25%), lymphocytes (16.65%), and basophils (30%), and an increase in the number of eosinophil (50%). Furthermore, number of monocytes and platelets decreased (10%) as the dose of the hormone increased. These results were alike for both groups of the rats irrespective of their age. The effect of rHuEpo is probably mediated through its stimulatory receptors on the surface of hematopoietic stem cells. Meanwhile, it is also possible that this hormone could inhibit the synthesis of neutrophil growth factors, interleukins with stimulatory effect on RBC maturation, and platelet-stimulatory factors.

Patients with chronic, painful diseases often seek alternative therapy. Ginger is one of the most popular herbal medications for rheumatic diseases. However, there are few experimental documents on its beneficial effects. Therefore, in this study the effect of ethanolic ginger extract and placebo were examined on 80 patients with osteoarthritis. The patients were randomized into two treatment groups (control and ginger extract, n=40) and taken either two capsules containing 30 mg ginger extract or placebo daily for a period of one month. Acetaminophen was used as rescue medication throughout the study. The results showed that ginger extract was more effective than placebo in reducing mechanical and gelling pain in patients with osteoarthritis. Furthermore, there were not any side effects during the treatment period with these medications. Taken together, it is concluded that instead of non-steroidal anti-inflammatory drugs, ginger extract might be used as a suitable alternative medicine and/or supplementation in reducing the pain in patients with osteoarthritis.

Estrogen has a widespread and complex influence on brain capabilities such as learning and memory. On the other hand, hippocampus as one of the main brain structures has an important role in spatial information processing. There is some evidence on the existence of estrogen receptors in the hippocampal CA1 area. So, in this study the effect of intrahippocampal injection of estradiol benzoate on spatial learning and memory were investigated in intact and castrated adult male NMRI rats The animals were randomly divided into eight groups and bilaterally cannulated (n=7). The intact and castrated control groups (no injection) were only trained in Y-maze. The castrated and intact rats received sesame oil vehicle, sham physiological saline and estradiol. Test groups received bilaterally 0.5 µl of sesame oil, 0.5 µl of physiological saline, and 1 µg/0.5 µl of estradiol benzoate respectively into the CA1 region of hippocampus immediately before training. Then, each rat was trained in 30 trials every day for a total of 5 days with Y-maze. After one month, all of the groups were again tested (one session) for memory performance. Statistical analysis of data showed that estradiol increases spatial learning in both castrated and intact groups. There was also no significant difference between castrated and intact groups regarding memory performance. In conclusion, it seems that estradiol increases spatial learning task through an interaction with cholinergic system and an enhancement of synaptic plasticity in CA1 region.

In this research study, the effect of bac10fen (GAB AB receptor agonist) on mean concentration of growth hormone, thyroxine, and triiodothyronine was examined. For this purpose, twelve Holstein cows were divided into four groups. Then, each cow received daily injection of 25, 50, 75, and 100 mg/kg of baclofen for a period of four days. Blood samples were daily collected at one time point for eight days. Growth hormone, thyroxine, and triiodothyronine concentrations of plasma samples were measured by RIA (Radioimmunoassay) method. The results showed that baclofen increases mean plasma concentration of growth hormone and thyroxine (P<0.01). In addition, low doses of bac10fen decreased mean plasma concentration of triiodothyronine (P<0.05), while 100 mg/kg of baclofen increased mean plasma concentration of triiodothyronine (P<0.05).