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)

Serum concentrations of the cytokine, interleukin-6 (IL-6), increase after surgical trauma. IL-6 mediates the synthesis of acute phase proteins and stimulates secretion of pituitary hormones. We have examined the time course of circulating IL-6, and cortisol and growth hormone responses in patients undergoing hysterectomy to determine if IL-6 contributes to the early pituitary hormone changes found during surgery. One group (n = 8) received a standardized general anaesthetic while the remaining patients (n = 8) received extradural analgesia to T4-S5 in addition to a similar general anaesthetic. In the general anaesthesia group, there was a significant increase in serum cortisol and growth hormone concentrations before any changes in IL-6 were detected. Furthermore, in the extradural group, in whom these hormonal responses were attenuated, circulating IL-6 concentrations did not differ significantly from the general anaesthesia group. There were no significant differences between the groups in the acute phase response, as measured by circulating concentrations of C-reactive protein and zinc, but the expected effects of extradural block on circulating metabolites and white cell count were demonstrated. We conclude that IL-6 is unlikely to contribute to the initial increases in secretion of pituitary hormones found during surgery, but a later effect of the cytokine on endocrine responses cannot be excluded.
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PMID:Effects of extradural anaesthesia on interleukin-6 and acute phase response to surgery. 751 May 10

The aim of this study was to demonstrate the effect of intra-articular morphine following knee arthroscopy performed in infiltration analgesia. Fifty-two healthy patients were randomized to receive either 1 mg of morphine or placebo. The pain was assessed 2, 4, 8 and 24 h after the procedure by (1) a VAS scale and (2) the amount of acetaminophen consumed. Demographic data in the 2 groups were similar. The pain scores at 8 and 24 h and the acetaminophen consumption after 8 h were lower in the morphine group (P < 0.05). Our results support the hypothesis of peripherally distributed opioid receptors. Stratifying data in therapeutic versus diagnostic arthroscopy indicated additional effect of morphine in patients undergoing therapy (P < 0.1), an aspect supporting the hypothesis of peripherally administered morphine as a potential suppressor of the substance P-mediated cytokine cascade and the peripheral leukocyte activity. Intra-articular morphine (1 mg) after knee arthroscopy offers efficient analgesia lasting more than 24 h. The method is devoid of side effects and deserves wider recognition.
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PMID:Low-dose intra-articular morphine analgesia in day case knee arthroscopy: a randomized double-blinded prospective study. 800 5

The purpose of this study was to demonstrate the effect of intra-articular morphine following knee arthroscopy performed in infiltration analgesia. Fifty-two healthy patients were randomized to receive either morphine 1 mg or placebo. The pain was assessed two, five, eight and 24 hours after the procedure by 1) a VAS scale and 2) the amount of acetaminophen consumed. Demographic data in the two groups were similar. The pain scores at eight and 24 hours and the acetaminophen consumption after eight hours were lower in the morphine group (p < 0.05). Our results confirm the hypothesis of peripherally distributed opioid receptors. Stratifying data in therapeutic vs. diagnostic arthroscopy suggests an additional effect of morphine in patients undergoing therapy (0.05 < p < 0.10), an aspect which supports the hypothesis of peripherally administered morphine acting as a potential suppressor of the substance P mediated cytokine cascade. Intraarticular morphine 1 mg after knee arthroscopy offers efficient analgesia lasting more than 24 hours. The method is devoid of side effects and deserves wider recognition.
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PMID:[Analgesic effect of low-dose intra-articular morphine after ambulatory knee arthroscopy]. 827 40

The peri-operative cytokine response was studied in 13 infants and young children undergoing major surgery. All children were anaesthetized with a combined general and epidural anaesthetic technique, followed by post-operative epidural analgesia with bupivacaine and fentanyl. Blood samples were taken before and after surgery, 24 h post-operatively, and finally, when the children were mobilized and had regained gastrointestinal function. Plasma samples were analysed for tumour necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interferon-gamma, interleukin-10 and the interleukin-1 receptor antagonist. The cytokine responses were highly variable. Overall, no significant changes between pre- and post-operative plasma concentrations were found. Tumour necrosis factor-alpha and the interleukin-1 receptor antagonist were detectable in all children, and a trend towards an early increase in the interleukin-1 receptor antagonist levels at the end of surgery was seen. The other cytokines were only detectable at low concentrations among a minority of children. In conclusion, this study showed highly variable peri-operative cytokine responses in infants and young children undergoing major surgery.
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PMID:The peri-operative cytokine response in infants and young children following major surgery. 952 42

Among nonsteroidal anti-inflammatory drugs (NSAIDs), 2-arylpropionic acids exist as a racemic mixture of its enantiomeric forms, with S-enantiomers primarily responsible for inhibition of prostaglandin synthesis and of inflammatory events. The aim of this study was to compare the anti-inflammatory effects of R- and S-ketoprofen in vitro and in vivo. S-Ketoprofen efficiently inhibited carrageenan-induced edema formation, but it could also amplify the LPS-induced production of the inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1), in close correlation with its ability to inhibit prostaglandin synthesis. Because these inflammatory cytokines are among the factors involved in carrageenan-induced inflammation and also are possibly involved in gastric damage, enhanced cytokine production could partially mask the analgesic effect of S-ketoprofen, and it can be associated with the clinical evidence of its gastric toxicity. On the other hand, R-ketoprofen contributes to the overall activity of the racemate, by playing the main role in ketoprofen-induced analgesia. Unlike the S-isomer, R-ketoprofen did not induce a significant increase of cytokine production even at cyclooxygenase-blocking concentrations. It is concluded that the R-isomer directly contributes to the anti-inflammatory effects of ketoprofen, being more analgesic, and because it does not amplify inflammatory cytokine production.
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PMID:Differential contribution of R and S isomers in ketoprofen anti-inflammatory activity: role of cytokine modulation. 986 81

Interleukin-6 (IL-6) plays a major role in hematopoiesis, immune functioning, and the acute phase response. In umbilical cord blood, this cytokine was thought to be a marker of neonatal defense to stress and infection, however, neonatal IL-6 production is immature. We speculated that a maternal influence exists on neonatal IL-6, at least during uncomplicated deliveries. Of the 81 healthy parturients included in this study, 51 delivered vaginally, 20 with and 31 without epidural analgesia, and 30 underwent elective cesarean section, 20 with epidural and 10 with general anesthesia. Maternal blood was sampled on hospital admission and just after delivery. Neonatal blood was collected from the umbilical cord. A significant positive correlation was found between neonatal cord blood interleukin-6 levels and maternal serum IL-6 levels on admission (r = 0.57, p <0.001) and just after delivery (r = 0.79, p <0.001). This was not influenced by the type of delivery or anesthesia. Neonatal IL-6 levels were weakly negatively correlated with the duration of gestation and with the Apgar score 1 min after birth. A feto-maternal dependency of neonatal IL-6 on maternal serum IL-6 levels implies a priming or modulatory role of the maternal immune system on that of the neonate.
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PMID:The fetomaternal dependency of cord blood interleukin-6. 1043 93

The pediatric metabolic response to injury and operation is proportional to the degree of stress and causes an increase in the turnover of proteins, fats, and carbohydrates. Thereby, substrates are made readily available for the immune response and wound healing. Because this process requires energy, the resting energy expenditure of ill patients increases. Whole-body protein degradation rates are elevated out of proportion to synthetic rates, and negative protein balance also ensues. Neonates and children are particularly susceptible to the loss of lean body mass and its attendant increased morbidity and mortality caused by an intrinsic lack of endogenous stores and greater baseline requirements. An appropriately designed mixed fuel system of nutritional support replete in protein does not quell this metabolic response but can result in anabolism and continued growth in ill children. In addition, the use of adequate analgesia and anesthesia is a readily available and proven means of reducing the magnitude of the catabolism associated with operation and injury. Finally, as hormonal- and cytokine-mediated metabolic alterations are better understood, therapeutic interventions may become available to directly modulate the metabolic response to illness, thus potentially further improving clinical outcome in pediatric surgical patients.
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PMID:The metabolic needs of critically ill children and neonates. 1046 26

The acid metabolites of THC were discovered almost 30 years ago and were later shown to posses modest analgesic and anti-inflammatory activity in a variety of models. Ajulemic acid (CT3) is a more potent analog of THC-11-oic acid in which a dimethylheptyl side chain is substituted for the pentyl side chain of the naturally occurring metabolite. It produces analgesia in the mouse hot plate, the PPQ writhing, the formalin and the tail clip assays. In the latter, it was equipotent to morphine; however, it showed a much greater duration of action. In the paw edema, subcutaneous air pouch and rat adjuvant-induced arthritis models of inflammation; it showed significant therapeutic activity at a dose of 0.2 mg/kg p.o. In the arthritis model it greatly reduced permanent damage to joints when compared to an indomethacin control as evidenced by an improved joint score over vehicle controls and by histopathological examination. In contrast to the NSAIDs, it was totally nonulcerogenic at therapeutically relevant doses. Moreover, it does not depress respiration, exhibit dependence, induce body weight loss or cause mutagenesis. It shows none of the typical actions in models of the psychotropic actions of cannabinoids suggesting that a good separation of desirable from undesirable effects was achieved. Studies on its mechanism of action are currently underway. The data thus far suggest the existence of a novel receptor for ajulemic acid with possible downstream effects on eicosanoid production, cytokine synthesis and metalloprotease activity. There is also circumstantial evidence for a putative endogenous ajulemic acid, namely, arachidonylglycine.
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PMID:Ajulemic acid (CT3): a potent analog of the acid metabolites of THC. 1090 96

Postoperative pain, arising due to surgical tissue injury, is most frequent type of pain found in clinical practice. In postoperative analgesia opioids still constitute the fundamental form of pain treatment, but the development of neurophysiology and neuropharmacology has allowed for the optimization of postoperative analgesia. Therefore, in order to potentialize the pain relief effect of opioids and/or inhibit the nociception process and its consequences, diverse drugs and therapies are used. The procedure is called multimodal analgesia and consists in the administration of opioids in conjunction with NMDA antagonists, COX inhibitors, cholecystokinin antagonists, agonists of muscarine receptors, agonists of alpha-2 receptors or cytokine inhibitors. An alternative or supplementary therapy in the postoperative period relies on local anaesthetic techniques or TENS. There also exists pre-emptive analgesia, whose aim is to safeguard the central nervous system from increased afferent nociceptive stimulation during the operation.
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PMID:[Postoperative pain treatment]. 1096 35

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


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