Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review summarizes our studies using pharmacological, neurochemical and molecular biological methods on the nociception in the CNS and opioid receptors (OPRs). We designed an in vitro fluorometric on-line monitoring system including an immobilized glutamate dehydrogenase column, and for the first time actually demonstrated that capsaicin induced the release of glutamate from rat dorsal horn slices containing the terminal area of primary afferents, in concentration-dependent, extracellular Ca(2+)-dependent and tetrodotoxin-resistant manners. Further, such a release was shown to be inhibited through mu- and delta-opioid receptors and alpha 2-adrenoceptors. On the other hand, we found that intracerebroventricular injections of interleukin (IL)-1 beta in rats produced biphasic effects on the mechanical nociception in rats (hyperalgesia in lower concentrations but analgesia in higher ones) and that similar injections of cytokine-induced neutrophil chemoattractant-1 (CINC-1) facilitated mechanical nociception in rats. The above described facts suggest that glutamate and some sorts of cytokines (IL-1 beta and CINC-1) contribute to nociception at least from the primary afferents to the spinal dorsal horn neurons and in higher brain, respectively. We have cloned rat kappa- and mu-opioid receptors. Using cloned cDNA for OPRs, we demonstrated (1) the distribution of mRNAs for OPRs in the rat central nervous system, (2) coexistence of each type of mRNA for mu-, delta- and kappa-OPRs and pre-protachykinin A mRNA in the dorsal root ganglion neurons, (3) an increased expression of mu- and kappa-OPR mRNAs in the I-II layers of rat lumbar dorsal horn with an adjuvant arthritis in the hind limb, (4) the inhibitions of N- and Q-types of Ca2+ channels by mu- and kappa-OPR agonists and (5) cross-desensitization of the inhibition through a common intracellular phosphorylation-independent mechanism, (6) pharmacological characterization of "antagonist analgesics" as partial agonists at every type of OPRs, and (7) the key-structure(s) of OPRs for discriminative binding of DAMGO to mu-OPR.
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PMID:[Molecular neuropharmacology of nociceptive transmission and opioid receptors]. 1119 80

A placebo-controlled, randomized blind study was conducted in cats (n = 60) after fracture repair to compare the analgesic effects as well as the side-effects of carprofen, buprenorphine and levomethadone during a 5-day treatment. Cats with severe shock symptoms or increases in blood urea nitrogen (BUN) and creatinine were excluded from the study. The cats were randomly assigned to four groups (n= 15). In group 1, carprofen was administered upon extubation at an initial dose of 4 mg/kg body weight, followed by one-third of that dose three times daily on days 2 to 5. In group 2, buprenorphine was administered in a single dose of 0.01 mg/kg body weight upon extubation and subsequently every 8 h. Levomethadone (group 3) was applied according to the same scheme at a dosage of 0.3 mg/kg body weight each time. The placebo (group 4) was given at the same time intervals as the opioids. Examinations were carried out prior to anaesthesia, between 30 min and 8 h after extubation, and on the following 4 days, 1 h after administration of the analgesics or the placebo as well as 1 h before the next administration. Pain and sedation evaluation was carried out with a visual analogue system (VAS) and with the aid of a numerical estimation scale (NRS). Pain was also scored by measuring mechanical nociceptive threshold of traumatized tissue. Plasma glucose and cortisol concentration, heart rate, respiration rate, blood pressure and body temperature were measured. Furthermore, a complete blood count and clinical chemistry including BUN, creatinine, alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), arterial blood pressure (AP), total protein and electrolytes of the cats were checked on the day of admission as well as on the last day of this study (day 5). Defaecation and urination as well as wound healing were monitored. On the basis of the mechanical nociceptive threshold of the traumatized tissue, concentrations of plasma glucose and cortisol and pain assessment using NRS and VAS, carprofen was found to have better anti-nociceptive efficacy when compared with the two opioid analgesics, while the analgesic effect of levomethadone was similar to that of buprenorphine. However, the carprofen group also showed comparably high median NRS and VAS pain scores in addition to occasional broad deviations from the group mean on the first post-operative treatment day. Sedative effects were detected for buprenorphine and levomethadone; in addition, symptoms of central excitation were noted with levomethadone. There was no indication of any clinically relevant respiratory depressive or cardiovascular effects, nor of any undesired renal, gastrointestinal or hepatic effects of the analgesics applied. However, the somewhat insensitive examination methods did not permit sufficient evaluation of side-effects, particularly on the gastrointestinal tract and the kidneys. It was found that carprofen and buprenorphine were well-tolerated analgesics for a 5-day administration in the cat, whereas levomethadone caused central excitation in some cases in the dosage scheme used here. However, it was apparent that none of the tested analgesics induced sufficient analgesia in the post-operative phase. For this reason, suitable methods must be found to improve analgesia, particularly in the immediate post-operative phase.
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PMID:Anti-nociceptive efficacy of carprofen, levomethadone and buprenorphine for pain relief in cats following major orthopaedic surgery. 1588 4