1,721,309 research outputs found
FEEDBACK CONTROL OF A MICHELSON INTERFEROMETER FOR ROUTINE LIFETIME CHARACTERIZATION IN CRYSTALLINE SILICON SOLAR CELLS
No full textSerotonergic and opiatergic modifications induced by paracetamol as a model for daily chronic headache with analgesic overuse
No full textThe chronic use of analgesic compounds may contribute to the chronicization of headache. It has been proposed that these headaches associated with daily drug use are due to a rebound effect in a vicious circle drug-headache–drug that mimics drug abuse (Post RM, Silberstein SD, Neurology; 44: 37-4,1994).There are several models to study experimental headaches in relation to acute antimigraine therapy (DeVries et al, Europ J Pharmacol 375: 61-74, 1999), whereas are lacking animal modelsf or daily chronic headache.Paracetamol is a drug widely used to treat headache, and often used in chronic headache sufferers. To explore the possible influence of this drug we performed a study to evaluate the effects of this drug on serotonergic and opiatergic systems in the rat brain after a sub-chronic administration.7 male Wistar rats groups of 8 animals were treated for 7 days with paracetamol i.p. at the dose of 400 mg/kg dissolved in a vehicle volume of 10 ml/kg or vehicle. Animals were submitted to hot-plate test every day at time 2,8 and 24 hours after drug administration. After this test one group of animals was sacrificed every day; the day 1 and 7 also control group were killed. Brains were dissected to determine the presence of binding sites for 5HT2 receptors in cerebral cortex by binding 3H-ketanserin and for opiate receptors by competitive binding with 3H-DAMGO.The results were analysed with Student’s test and Mann-Whitney U test for motor activity. Data were expressed as mean } S.E. Motor activity was not different in vehicle or in paracetamol treated rats at days 1 and 7 ( P> 0.05) . The % of MPE in hotplate test was 5.1}3.2 and 4.7}2.5 at day 1 and 7 for vehicle treated rats, and 24.5}8 and 19.7}4.3 at day 1 and 7 for paracetamol treated rats (P0.5).Paracetamol treated rats Bmax was 194}12.3 and 187}21 fmol mg/prot at day 1 and 7 respectively for ketanserin ( p>0.05), and 250}32 and 170}24 fmol mg/prot at day 1 and 7 respectively for DAMGO (P<0.05). Treatment reduced significantly both types of receptor with respect to vehicle.Repeated doses of paracetamol do not induce tolerance in hotplate test. This treatment induces, as expected, a stable reduction of Bmax in cerebral cortex of 5-HT2 and receptors. These receptors were reduced after a week treatment, whereas the antinociceptive activity was maintained. These data suggest that the prolonged antinociceptive effect of paracetamol is linked more to serotonergic than opiatergic system.This lack of tolerance in analgesic effect of paracetamol could be important to explain the choice of this drug by patients suffering from chronic headaches
The effect of chronic treatment with phenazone on [3H]-serotonin binding sites in pons and cortex membranes of the rat
No full textWe studied 36 male rats, 18 o them were trated orally for 30 days with 60 mg/kg/day of phenazone and 18 used as controls. Our data show that a chronic treatment with phenazone increases the number of serotonin receptors in two brain areas while the affinity is not modified; in the same model we demonstrated that phenzone modifies noradrenergic pontine receptors. The role of these changes in receptors characterstics after a long-term treatment with phenazone may contribute to the antinociceptive effect of phenazone
THE ROLE OF SEROTONIN BRAIN RECEPTORS IN THE ANALGESIC EFFECT OF PHENAZONE
No full textThe effects of treatment with para-chloro-phenyl-alanine (PCPA) (100 mg/kg i.p. for 4 days) were studied on the hot-plate test and on brain 5-HT binding in phenazone treated rats. Phenazone per se induces analgesia in the hot-plate test and decreases the number of cortical and pontine 5-HT binding sites. A pre-treatment with PCPA prevents both the analgesic effect and the reduction of 5-HT binding sites caused by phenazone. These data suggest that the brain serotonin system may play a role in phenazone-induced antinociception
Lack of activity of Ketorolac in hot-plate test and serotonin binding capacity of brain membranes in rats
No full textAn increasing number of observations indicate that prostaglandin synthesis inhibition is not a satisfactory explanation for the antinociceptive activity of the non-steroidal anti-inflammatory drugs. In the hot-plate test performed 1 or 2 h after ketorolac at 40, 70 and 100 mg/kg i.p., the drug does not display any significant antinociceptive activity. Nor, at the two higher doses used, does it affect the cortical and pontine serotonin binding capacity of rat brain membranes 2 h after treatment. The data suggest that this lack of antinociceptive activity in the hot-plate test is associated with the drug's inability to affect the central serotoninergic system
Central antinociceptive activity of acetylsalicylic acid is modulated by brain serotonin receptor subtypes
No full textMale Wistar rats were treated with ondansetron (1 and 2 mg/kg s.c.), ketanserin (0.2, 1 and 5 mg/kg s.c.) or NAN-190 (1, 3 and 5 mg/kg i.p.) 15 min before acetylsalicylic acid (ASA, 400 mg/kg i.p.), and 30 min thereafter the pain threshold was evaluated. The antinociceptive activity of ASA in the hot-plate test was variously affected by ondansetron, ketanserin and NAN-190: at the highest dose (2 mg/kg s.c.) ondansetron abolished it while ketanserin (5 mg/kg s.c.) significantly reduced it, and NAN-190 (1-5 mg/kg) did not significantly modify the effect of ASA. Binding experiments indicate that both ondansetron and ketanserin completely prevented the decrease in the maximum number of 5-HT2 receptors (B-max) provoked by ASA. These data indicate that the central antinociceptive activity of ASA is modulated in a different manner by serotonin receptor antagonists, and that 5-HT2 and 5-HT3 receptors may exert a pivotal role in nociception, alone or in association. Copyrigh
Differential involvement of central 5-HT1B and 5-HT3 receptor subtypes in the antinociceptive effect of paracetamol
No full textObjective: We investigated the effect of pre-treatment with ondansetron or CP 93129 (a 5-HT1B agonist) on the antinociceptive activity of paracetamol and the changes in central 5-HT3 receptors induced by paracetamol alone or co-administered with ondansetron. Materials and Subjects: Male Wistar rats (eight per group) were injected with ondansetron (2 and 4 mg/kg s. c.) or CP 93 129 (0.5, 1 and 2 mg/kg s. c.) 15 min before paracetamol (400 mg/kg, i.p.). Methods: Pain threshold was evaluated in the hot-plate or in the paw pressure test 30 min after the last treatment. 5-HT3 receptor binding capacity was measured in the frontal cortex, temporal-parietal cortex and midbrain by means of radioligand binding technique. Statistical analysis was done using ANOVA followed by Student-Newman-Keuls test and 2 X 2 factorial analysis when appropriate. Results: Pre-treatment with ondansetron, at doses of 2 and 4 mg/kg, did not affect the antinociceptive activity of paracetamol in the hot-plate test and in the paw pressure test. Paracetamol did not change the characteristics of 5-HT3 receptors in all the areas investigated. Ondansetron (4 mg/kg s. c) per se significantly increased the 5-HT3 receptor number in the areas used, the effect not being modified by co-administration with paracetamol. On the other hand, CP 93129 (2 mg/kg s. c.) significantly prevented the effect of paracetamol in both algesimetric tests used. Conclusions: Our data indicate that 5-HT1B but not 5-HT3 receptors are involved in the antinociceptive effect of paracetamol in our experimental conditions
Serotonin and opiate involvement in the antinociceptive effect of acetylsalicylic acid
No full textAcetylsalicylic acid (ASA), 400 mg/kg i.p., displayed antinociceptive activity in both the hot-plate and the formalin test, ASA significantly increased brain serotonin (5-HT) content and reduced the number of 5-HT2 receptors in cortical brain membranes 30 min after drug administration, Pretreatment with naloxone abolished the antinociceptive activity of both ASA and morphine in the hot-plate and formalin tests and prevented the increase in cerebral 5-HT concentration and the reduction in 5-HT2 receptors in cortical membranes induced by ASA, The serum salicylate concentrations were not affected by pretreatment with naloxone, These data indicate a central antinociceptive activity of ASA and suggest that ASA may exert its antinociceptive action through serotonergic and opiatergic pathways
Involvement of brain serotonergic system in the antinociceptive action of acetylsalicylic acid in the rat
No full textThe pain-threshold in the hot-plate test and serotonin (5-HT) receptor binding capacity in the cortex and pontine areas of rat brain were studied after intraperitoneal (ip) administration of acetyl salicylate of lysine equivalent to 400 mg/kg of acetylsalicylic acid (ASA). The antinociceptive activity of ASA was prevented by ip pre-treatment with Parachlorophenylalanine (PCPA) at the rate of 100 mg/kg/day for 4 days. PCPA pre-treatment increased the number of 5-HT receptors and abolished the ASA-induced reduction in 5-HT receptor binding capacity in the cortex but did not affect serum salicylate levels. These results provide support for the hypothesis that the antinociceptive action of ASA, at least in the hot-plate test, involves the central serotonergic system
- …
