Antioxidant activity in rat models of nociceptive stress.

UNLABELLED: Pain is an important problem and has been the subject of many studies in recent years. MATERIAL AND METHOD: The present study has investigated the response of the antioxidant defense systems in contention stress, which mimics nociceptive stress. Contention stress was made by immobilizing the rat, Wistar rats, on an operating table in a specific position with paws tied, for thirty minutes. The determinations evaluate the levels of oxidative stress markers like reduced glutathione (GSH) and malondialdehyde (MDA) and the levels of the protecting enzymes against of free radicals in brain. RESULTS: After the application of contention stress, GSH level increased insignificantly, while MDA level increased significantly compared with the normal animals. These have demonstrated that in our model of nociceptive stress actioned the mechanisms of membrane lipid peroxidation. The activity of the antioxidant enzymes GSH, GPX and SOD decreased in the stressed animals compared with the normal group. This experiment has revealed that in our model of nociception stress, many reactive oxygen species (ROS) were generated, which reduced the enzymatic defense mechanisms and activated lipid peroxidation mechanisms.

New technical approaches in stereotaxic catheterization of cerebral ventriculi: implications for the L-arginine/NO synthase/nitric oxide cascade.

In order to study the actions of certain substances at cerebral level, a stereotactic device for ensuring a precise catheterization of points in certain cerebral areas was used. For the operation technique was used a stereotaxic atlas specifically designed for rat brain (G. Paxinos, C. Watson, 1998), which offers all the necessary information for the identification of the trepanation. Stereotaxic implantation of cannules in the brain is useful for microinjecting solutions containing various substances (in amounts of microl), directly and targeted in the anatomical structures of the brain. The technique described can use either metalic or silastic cannules, that have variable lumen (usually for adapting a Hamilton syringe). The cannules can be implanted at cerebroventricular level, having the possibility to target all the cerebral ventricles. The intracerebroventricular (icv) administration of L-arginine induces a significant increase of response latency for mechano-algesic test. The most obvious changes are induced following the administration of the association of L-NAME with L-arginine, situation when is manifested an important increase of the response latency, starting with 5 minutes post-administration and continuing up to 45 minutes determination. The increase is significantly higher compared with the results obtained with L-arginine alone. A similar evolution is registered in the case of the plantar test.

Experimental data regarding the implications of certain minimum structure enkephalin-like peptides in nociceptive processing.

The aim of this study was to investigate the importance of the amino acidic sequence at N-terminal end of certain minimum structure enkephalin-like peptides for the analgesic activity. Different groups of mice or rats were treated with 1) L-tyrosine (i.p. 200 mg/kg), 2) Tyr-Phe (i.t. 0.5 mg/rat), 3) Tyr-Pro-Phe (i.t. 0.5 mg/rat), 4) Gly-Tyr (i.t. 0.5 mg/rat), 5) Tyr-Gly-Gly (i.t. 0.5 mg/rat). Different tests were utilized to evaluate the antinociceptive effect of the substances tested: thermal nociception (hot plate test, plantar test), mechanical nociception (analgesymeter test). Tyr-Pro-Phe, Tyr-Gly-Gly, Tyr-Phe, but not Gly-Tyr, elicited analgesic activity. So, the presumption made in the case of atypical opioid peptides that opioid-like activity in case of peptides presumes a tyrosine residue at the N-terminal sequence, applies for shorter peptides. It appears also that minimal structure brain peptides with an N-terminal Tyr-Pro, rather than the Tyr-Gly-Gly-Phe sequence typical of other endogenous opioids, can provide better affinity for the opioid receptors and stronger analgesic activity. The inhibition of their analgesic effect by previous administration of naloxone proves that this effect is mediated through the endogenous opioid system.