Differential modulation of nociceptive responses to mu and kappa opioid receptor directed drugs by blood glucose in experimentally induced diabetes rats.

The study has evaluated the effect of diabetes associated hyperglycaemia on nociception and antinociception induced by morphine, buprenorphine and pentazocine in female albino rats. Rats were allocated into 3 groups of 20 each--group I consisted of control having normal blood glucose levels (BGLs), group II consisted of streptozotocin-induced diabetics (STZ-D) having hyperglycaemia and group III consisted of diabetic rats controlled with insulin treatment. Immediately before and 15, 30 min, 1, 2 and 3 hr after injection with test drugs, rats were subjected to a thermal noxious stimulus using tail withdrawal from hot water and tail-flick latencies (TFL) so generated were recorded. Similarly, before and 30, 45 min and 1 hr after injection with drugs rats were subjected to abdominal writhing with hypertonic saline and number of writhes were counted per 90 sec. In STZ-D animals (BGLs 317.95 +/- 3.8 mg/dl) a decreased TFL with an increase in the number of writhes compared to control and diabetes controlled with insulin treatment was observed. Percent maximum possible effect of morphine (5 mg/kg, s.c.) and buprenorphine (2 mg/kg, s.c.) was significantly lower when compared to control as well as STZ-D controlled with insulin treatment groups. Similarly percent protection from writhing of morphine (0.05 mg/kg, s.c.) and buprenorphine (0.01 mg/kg, s.c.) was significantly less in comparison to control and STZ-D controlled with insulin treatment group. However, percent maximum possible effect of pentazocine (20 mg/kg, s.c.) and percent protection from writhing of pentazocine (1 mg/kg, s.c.) was significantly high in STZ-D rats when compared to control and STZ-D rats controlled with insulin treatment groups. The results suggest that both mu and kappa--opioid receptors may be modulated by blood glucose levels possibly involving cellular energetics mediated change in potassium (KATP) channels in females rats, albeit differentially.

Tramadol, a centrally acting opioid: anticonvulsant effect against maximal electroshock seizure in mice.

The present study was designed to investigate the pro- or anticonvulsant effect of tramadol using maximal electroshock (MES) test. An attempt was also made to determine the possible opioid receptor mechanism involved. MES seizures were induced through transauricular electrodes (60 mA, 0.2s) and the seizure severity was assessed by the duration of tonic hindlimb extensor phase. Intraperitoneal (i.p.) administration of tramadol resulted in a dose-dependent anticonvulsant action; the ED50 for the effect was 33 mg/kg. The anti-MES effect of tramadol was antagonized by the low doses (0.05 and 0.1 mg/kg, s.c.) of MR 2266, a selective kappa receptor antagonist and also by the high doses (1.0 and 5.0 mg/kg, i.p.) but not the low doses (0.1 and 0.25 mg/kg) of naloxone. The results suggest that the anti-MES effect of tramadol is mediated by kappa receptors, since MR 2266 and naloxone (in high doses) are known to block these receptors.

Los péptidos opioides en el control del dolor / Opioid peptides in pain control

Este tabajo presenta un descripción breve de las evidencias que señalan el papel de los péptidos opioides en el control del dolor. Se describe el papel inhibidor de la ß-endorfina y de la Met-encefalina en los tejidos periféricos y, se sugiere una acción local en el sitio de la inflamación. Asimismo, se hace referencia a los sistemas endógenos de inhibición del dolor tanto a los segmentarios inherentes a la organización celular de la médula espinal, como a los sistemas descendentes, que tienen su origen en diversos núcleos del tallo cerebral. Las conexiones eferentes de estos sistemas siguen el trayecto del fascículo dorsolateral para terminar en las astas dorsales de la médula espinal, en donde ejercen su acción. Con esta idea, se analiza la participación de la ß-endorfina y los péptidos derivados en la analgesia. También se discute el papel que desempeñan los receptores µ, delta y kappa en el control del dolor y los ligandos endógenos que se unen a estos receptores. Las evidencias sugieren que la analgesia opioide, es el resultado predominante de la activación de los receptores µ, aunque los delta y los kappa pueden potenciar este efecto. Con respecto a los receptores delta y sus ligandos con mayor afinidad, las encefalinas tienen una participación indirecta en la analgesia. En relación a los receptores kappa y sus ligando más afines, las dinorfinas, los datos publicados son controvertidos. Por último, se hace referencia a los efectos paradójicos de la naloxona en el control del dolor, pues a dosis altas, aumentan las respuestas algésicas (hiperalgesia) y las dosis muy bajas producen analgesia

Role of kappa opioid receptors during stress responsiveness in rats.

Effects of kappa opioid agonist, ketocyclazocine (KCZ) and its antagonist, M(r) 2266, were evaluated on some stress responses in rats. KCZ (1 or 10 mg/kg, ip) dose-dependently attenuated cold restraint stress (CRS)-induced gastric ulcer formation. Similar gastric cytoprotection was also seen with KCZ (1 or 10 micrograms/rat, icv). Pretreatment of rats with M(r) 2266 (0.3 mg/kg, ip) clearly antagonized the ulceroprotective effects of both ip and icv KCZ. KCZ effects on the gastric mucosa during CRS were also reduced by naltrexone (5 mg/kg, ip) pretreatment. KCZ (1 or 10 mg/kg, ip) also attenuated the plasma corticosterone response to CRS and these effects were blocked by M(r) 2266 (0.3 mg/kg) pretreatment. These results indicate kappa opioid receptor involvement during stress reactions and also suggest possible opioidergic interactions during CRS.