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

Many of the nonsteroidal anti-inflammatory drugs (NSAIDs) are marketed as racemic mixtures, composed of (R)- and (S)- enantiomers. Racemic NSAIDs are potent cyclooxygenase (COX) inhibitors only through the action of the (S)- enantiomers, as the (R)- enantiomers do not exhibit COX inhibition. However, the (R)- enantiomer of ketoprofen exhibits potent analgesic activity and minimal ulcerogenic potential. To extend these observations, we examined the (R)- and (S)- enantiomers of RS- ketorolac, (S)- ketorolac exhibited potent COX1 and COX2 enzyme inhibition, whereas (R)- ketorolac was > 100-fold less active on both COX subtypes. Both enantiomers did not affect norepinephrine or serotonin uptake sites, and nitric oxidase or lipoxygenase activities, nor did they demonstrate any affinity for opioid receptors (mu, delta, or kappa). In experimental models, (S)- ketorolac exhibited about 10-fold greater activity than (R)- ketorolac in the murine phenylquinone writhing model. In this model, morphine sulfate was effective at much lower doses, however, and neither (R)- nor (S)- ketorolac showed any morphine-sparing effect. In the rat gait test for analgesia in the foot paw after injection of brewers yeast suspension, neither (R)- nor (S)- ketorolac affected paw volume. However, both provoked changes in gait scores, the (S)- enantiomer being 30-fold more potent than the (R)- enantiomer. A similar reduction was observed with respect to ulcerogenic potential, measured by direct microscopic changes after test conclusion. These findings suggest that (R)- ketorolac may possess analgesic activity that is independent of COX inhibition and may be associated with reduced ulcerogenic potential compared to effects exhibited by (S)- ketorolac.
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PMID:Preclinical enantioselective pharmacology of (R)- and (S)- ketorolac. 954 56

Analgesia is an intrinsic part of anesthesia, and the use of opioids for premedication, supplementation of anesthesia, and postoperative analgesia is not new. Development of new potent and less toxic NSAIDs has now resulted in this type of analgesic, also playing a major role in perioperative analgesia. Weak cyclo-oxygenase inhibitors, and NSAIDs with high COX2 activity, are proving successful in the provision of analgesia in dogs and cats. Some newer opioids developed for man have potential for use in dogs and cats, and buprenorphine, a partial agonist, deserves further evaluation. Some novel analgesics have potential for use in animals, but the specific analgesic role of old friends ketamine and the alpha 2 adrenoceptor agonists is worthy of closer scrutiny.
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PMID:Newer analgesics. Nonsteroid anti-inflammatory drugs, opioids, and combinations. 1033 19

Nowadays, postoperative pain control in infants and children is a big challenge. The only effective solution is a multidisciplinary work with accurate guidelines, starting from the preoperative period throughout the surgery and arriving at the postoperative period. The approach must be scientific, based on the recent studies and research. In recent years, there has been a renaissance in regional anesthesia in children, in part because of a greater concern about postoperative pain management in young patients, and in part because of technical advances in equipment to perform the blocks. In fact several techniques and routes can be used for pain treatment but all have side effects. We await data from the use of COX2 inhibitors, surely the future of NSAIDs, with valid anti-inflammatory action and fewer side effects in children. When possible/not controindicated, regional analgesia is often the best choice. Recently continuous peripheral infusion is successfully applied in infants and children, due to its safety, efficacy and well limited localisation of analgesia. All the variety of peripheral nerve blocks used in adults can be used in pediatrics. The indications to place a catheter for a continouos peripheral nerve blocks are the followings: major orthopedic procedures; the procedure is scheduled to last more than two hours; congenital malformation of foot or hand; fracture reduction; traction of femur fracture; when postoperative pain therapy is necessary for several days; painful physical therapy. The commonly performed continuous peripheral blocks in children are the brachial plexus block (parascalene or axillary), the femoral nerve block, the fascia iliaca block, the sciatic nerve block with the lateral or with the popliteal approach. In these last two years also our group performed several continuous peripheral nerve blocks particularly axillary, femoral and sciatic for major orthopedic surgery and trauma. In our institution, we use a bolus dose of 0.5-1 ml/kg (depending on the nerve to be blocked) of ropivacaine 0.2% or levobupivacaine 0.25% with clonidine 2 microg/kg and then in infants older than 6 months and children we use a continuous infusion of 0.1-0.3 ml/kg/h of 0.2% ropivacaine or 0.25% levobupivacaine with clonidine 3 microg/kg/24h for 48-72 hours. For older children doses and concentrations are usually the same used in adults.
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PMID:Postoperative analgesia in infants and children: new developments. 1518 22

Electroacupuncture (EA) is considered to be a promising alternative therapy to relieve the menstrual pain for primary dysmenorrhea (PD), but the conclusion is controversial. Here, we conducted a systematic review and meta-analysis specifically to evaluate the clinical efficacy from randomized controlled trials (RCTs) on the use of EA in patients with PD. PubMed, Embase, ISI Web of Science, CENTRAL, CNKI, and Wanfang were searched to identify RCTs that evaluated the effectiveness of EA for PD. The outcome measurements included visual analogue scale (VAS), verbal rating scale (VRS), COX retrospective symptom scale (RSS), and the curative rate. Nine RCTs with high risk of bias were included for meta-analysis. The combined VAS 30 minutes after the completion of intervention favoured EA at SP6 when compared with EA at GB39, nonacupoints, and waiting-list groups. EA was superior to pharmacological treatment when the treatment duration lasted for three menstrual cycles, evidenced by significantly higher curative rate. No statistically significant differences between EA at SP6 and control groups were found regarding the VRS, RSS-COX1, and RSS-COX2. The findings of our study suggested that EA can provide considerable immediate analgesia effect for PD. Additional studies with rigorous design and larger sample sizes are needed.
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PMID:Electroacupuncture is Beneficial for Primary Dysmenorrhea: The Evidence from Meta-Analysis of Randomized Controlled Trials. 2935 60

Prevalence of prior stressful experience is linked to high incidence of chronic pain. Stress, particularly repeated stress, is known to induce maladaptive neuroplasticity along peripheral and central pain transmission pathways. These maladaptive neuroplastic events facilitate sensitization of nociceptive neurons and transition from acute to chronic pain. Pro-inflammatory and pain mediators are involved in inducing neuroplasticity. Pain mediators such as prostaglandin E2 (PGE2), EP4 receptor and transient receptor potential vanilloid-1 (TRPV1) contribute to the genesis of chronic pain. In this study, we examined the role of PGE2/EP4 signaling and TRPV1 signaling in repeated restraint stress-induced prolongation of sensitization pain, a model for transition from acute to chronic pain, in both in vivo and in vitro models. We found that pre-exposure to single restraint stress induced analgesia that masked sensitization pain evoked by subsequent PGE2 challenge. However, pre-exposure to 3d consecutive restraint stress not only prolonged sensitization pain, but also increased stress hormone corticosterone (CORT) in serum, COX2 levels in paw skin, and EP4 and TRPV1 levels in dorsal root ganglion (DRG) and paw skin. Pre-exposure to CORT for 3d, not 1d, also prolonged sensitization pain evoked by PGE2. Co-injection of glucocorticoid receptor (GR) antagonist RU486, COX2 inhibitor NS-398, EP4 receptor antagonist L161,982 or TRPV1 antagonist capsazepine prevented 3d restraint stress prolonged sensitization pain evoked by PGE2. In DRG cultures, CORT increased EP4 and TRPV1 protein levels through GR activation. These data suggest that PGE2/EP4 signaling and TRPV1 signaling in peripheral pain pathway contribute to repeated stress-predisposed transition from acute to chronic pain.
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PMID:PGE2/EP4 receptor and TRPV1 channel are involved in repeated restraint stress-induced prolongation of sensitization pain evoked by subsequent PGE2 challenge. 3130 96