Life sciences
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C57BL/6J (B6) mice self-administer substantial quantities of morphine compared to DBA/2J (D2) mice, and most of the genetic component of this strain difference has been attributed to a locus on chromosome 10 in the vicinity of the mu opioid receptor gene. To compare binding characteristics of mu opioid receptor populations between the two strains, mice were given single daily injections of a long-acting preparation of morphine sulfate (80 mg/kg, s.c.) or saline for a period of seven days, and euthanatized six hours after the last injection. Brains were removed and dissected into specific regions. ⋯ After repeated morphine injection, B6 mice exhibited a decrease in striatal [3H]DAMGO binding, indicating a downregulation of receptor density by approximately 45% (p=.0003 vs saline-treated B6), a phenomenon not observed in D2 mice. In frontal cortex, no differences in [3H]DAMGO binding were observed between strains or treatment groups. These results demonstrate a significant difference between mu opioid receptor regulation in B6 and D2 mice, and may underlie well documented strain differences in specific opioid-related behaviors.
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At this time little is know about local anesthesia of the skin, and the sensitivity of different cutaneous regions to local anesthetics. Studies were conducted in mice to test the hypothesis that cutaneous regions are differentially sensitive to bupivacaine, and to the ability of epinephrine (EPI) to prolong local anesthesia. Infiltration of 0.25% and 0.5% bupivacaine s.c. in the dorsal aspect of the mouse tail produced local anesthesia that lasted 15 and 45 min, respectively, against radiant heat nociception. ⋯ Bupivacaine (0.25% and 0.5%) infiltrated in the dorsal aspect of the hind-paw produced local anesthesia that lasted 5 and 30 min, respectively. EPI prolonged the local anesthetic effects of the 0.25% concentration by only 10 min, whereas EPI did not prolong anesthesia but appeared to increase the efficacy of the 0.5% concentration. These results provide evidence of regional differences in cutaneous sensitivity to local anesthetics, and the ability of EPI to extend the duration of anesthesia.
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Review Historical Article
Euphorbium: modern research on its active principle, resiniferatoxin, revives an ancient medicine.
Resiniferatoxin, an ultrapotent capsaicin analog present in the latex of Euphorbia resinifera, interacts at a specific membrane recognition site (referred to as the vanilloid receptor), expressed by primary sensory neurons mediating pain perception as well as neurogenic inflammation. Desensitization to resiniferatoxin is a promising approach to mitigate neuropathic pain and other pathological conditions in which sensory neuropeptides released from capsaicin-sensitive neurons play a crucial role. Clinical trials to evaluate the potential of topical resiniferatoxin treatment to relieve pain associated with diabetic polyneuropathy and postherpetic neuralgia are in progress. ⋯ This review highlights the most important events in the history of this ancient medicine, from the first written record of the therapeutic potential of Euphorbium (at the time of the reign of the Roman Emperor Augustus) to the identification of its active principle as resiniferatoxin in 1975. A brief overview of the enormous contribution of resiniferatoxin to our current understanding of the anatomical localization, function, and pharmacology of vanilloid receptors is provided. Lastly, the mechanisms are summarized by which capsaicin and resiniferatoxin, despite sharing receptors, may have dissimilar biological actions.
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Tachyphylaxis to peripheral neural blockade was determined with repeated injections of a constant dose of lidocaine in three experimental models: sciatic nerve block, produced by intraneural or extraneural injections, and infiltration anesthesia. A decrease in the duration of the subsequent blocks was used as the index of tachyphylaxis development. The anesthetic content in the nerve or skin was determined using radiolabeled lidocaine. ⋯ Accelerated decline in lidocaine content of nerve or skin was observed with repeated blocks. Our data show that tachyphylaxis rapidly develops with both sciatic nerve blocks and infiltration anesthesia. The data also suggest that the mechanism is largely pharmacokinetic in nature.
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Comparative Study
Blood glucose and prolactin in hyperprolactinemic rats exposed to restraint and surgical stress.
The effects of chronic hyperprolactinemia on plasma prolactin (PRL) and glucose were investigated in male rats submitted to two different types of stress: restraint (60 min in a plastic tube) or surgery (laparotomy under ether anesthesia). Hyperprolactinemia was induced by grafting one homologous pituitary gland under the kidney capsule. Restraint stress induced a marked increase of plasma PRL of control rats with a peak at 15 min (increase of 403%), but did not change the PRL levels of hyperprolactinemic rats. ⋯ Grafted rats presented hyperglycemia during all the experimental period, whereas control rats showed glycemia similar to basal levels by the end of the experiment. In conclusion, different responses are induced depending on the type of stress: more intense PRL secretion is induced by restraint and higher hyperglycemia by surgery. Chronic hyperprolactinemia induced a higher (restraint) or longer lasting (surgery) hyperglycemic response in the rat, adding new evidence for a diabetogenic effect of PRL.