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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opiates are the primary treatment for pain management in cancer patients reporting moderate to severe pain, and are being increasingly used for non-cancer chronic pain. However, prolonged administration of opiates is associated with significant problems including the development of antinociceptive tolerance, wherein higher doses of the drug are required over time to elicit the same amount of analgesia. High doses of opiates result in serious side effects such as constipation, nausea, vomiting, dizziness, somnolence, and impairment of mental alertness. In addition, sustained exposure to morphine has been shown to result in paradoxical pain in regions unaffected by the initial pain complaint, and which may also result in dose escalation, i.e. 'analgesic tolerance'. A concept that has been gaining considerable experimental validation is that prolonged use of opioids elicits paradoxical, abnormal pain. This enhanced pain state requires additional opioids to maintain a constant level of antinociception, and consequently may be interpreted as antinociceptive tolerance. Many substances have been shown to block or reverse antinociceptive tolerance. A non-inclusive list of examples of substances reported to block or reverse opioid antinociceptive tolerance include: substance P receptor (NK-1) antagonists, calcitonin gene-related peptide (CGRP) receptor antagonists, nitric oxide (NO) synthase inhibitors, calcium channel blockers, cyclooxygenase (COX) inhibitors, protein kinase C inhibitors, competitive and non-competitive antagonists of the NMDA (N-methyl-D-aspartate) receptor, AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) antagonists, anti-dynorphin antiserum, and cholecystokinin (CCK) receptor antagonists. Without exception, these substances are also antagonists of pain-enhancing agents. Prolonged opiate administration indeed induces upregulation of substance P (SP) and calcitonin gene-related peptide (CGRP) within sensory fibers in vivo, and this is accompanied by an enhanced release of excitatory neurotransmitters and neuropeptides from primary afferent fibers upon stimulation. The enhanced evoked release of neuropeptides is correlated with the onset of abnormal pain states and opioid antinociceptive tolerance. Importantly, the descending pain modulatory pathway from the brainstem rostral ventromedial medulla (RVM) via the dorsolateral funiculus (DLF) is critical for maintaining the changes observed in the spinal cord, abnormal pain states and antinociceptive tolerance, because animals with lesion of the DLF did not show enhanced evoked neuropeptide release, or develop abnormal pain or antinociceptive tolerance upon sustained exposure to opiates. Microinjection of either lidocaine or a CCK antagonist into the RVM blocked both thermal and touch hypersensitivity as well as antinociceptive tolerance. Thus, prolonged opioid exposure enhances a descending pain facilitatory pathway from the RVM that is mediated at least in part by CCK activity and is essential for the maintenance of antinociceptive tolerance.
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PMID:Is paradoxical pain induced by sustained opioid exposure an underlying mechanism of opioid antinociceptive tolerance? 1621 2

Total rectal prolapse is a disabling disease. The aim of this study was to evaluate pain management, hospital stays, constipation, and continence status among military personnel who underwent laparoscopic surgery. Forty patients (mostly men) underwent laparoscopic rectopexy (LR) or laparoscopic resection rectopexy (LRR). Colonic transit time, postoperative pain scores, preoperative and postoperative anal function, and changes in constipation were assessed. The median operation times for LR and LRR were 126 and 223 minutes, respectively. The median postoperative hospital stays were 3 and approximately 6 days for LR and LRR, respectively. Patients needed fewer analgesics in a short postoperative period. However, there was no difference between the two groups in analgesic requirements. Continence improved for approximately 71% of patients, but constipation was treated for 50% of affected patients. No recurrences were noted in the follow-up periods, which were 13 and 22 months for the LRR and LR groups, respectively. The quality of life for the patients who underwent LR was not as good as that for the patients who underwent LRR, at the end of 1 year. We eliminated total rectal prolapse and almost cured incontinence by using laparoscopy, although the disadvantageous aspects were long operation times and suboptimal healing with respect to constipation and related symptoms. LRR is the more feasible procedure, with the emphasis on elimination of incontinence and constipation, producing a better quality of life for patients, in addition to short hospitalizations, necessity for analgesia for a short time, and return to hard training field activities in a short time among military personnel.
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PMID:The impact of laparoscopic resection rectopexy in patients with total rectal prolapse. 1626 77

Given the expanding role of ambulatory surgery and the need to facilitate an earlier hospital discharge, improving postoperative pain control has become an increasingly important issue for all anesthesiologists. As a result of the shift from inpatient to outpatient surgery, the use of IV patient-controlled analgesia and continuous epidural infusions has steadily declined. To manage the pain associated with increasingly complex surgical procedures on an ambulatory or short-stay basis, anesthesiologists and surgeons should prescribe multimodal analgesic regimens that use non-opioid analgesics (e.g., local anesthetics, nonsteroidal antiinflammatory drugs, cyclooxygenase inhibitors, acetaminophen, ketamine, alpha 2-agonists) to supplement opioid analgesics. The opioid-sparing effects of these compounds may lead to reduced nausea, vomiting, constipation, urinary retention, respiratory depression and sedation. Therefore, use of non-opioid analgesic techniques can lead to an improved quality of recovery for surgical patients.
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PMID:The changing role of non-opioid analgesic techniques in the management of postoperative pain. 1633 89

Opiate drugs such as morphine are well known for their ability to produce potent analgesia as well as such unwanted side effects as tolerance, physical dependence, respiratory suppression and constipation. Opiates act at opioid receptors, which belong to the family of G protein-coupled receptors. The mechanisms governing mu opioid receptor (muOR) regulation are of particular interest since morphine and other clinically important analgesics produce their pharmacological effects through this receptor. Here we review recent advances in understanding how opioid receptor regulation can impart differential agonist efficacy produced in vivo.
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PMID:Mu opioid receptor regulation and opiate responsiveness. 1635 37

In pediatric oncology, optimal pain control is still a challenge. A structured pain history and the regular scoring of pain intensity using age-adapted measuring tools are hallmarks of optimal pain control. Psychological measures are as important as drug therapy in the prophylaxis or control of pain, especially when performing invasive procedures. Pain control is oriented toward the WHO multistep therapeutic schedule. On no account should the pediatric patient have to climb up the "analgesic ladder" - strong pain requires the primary use of strong opioids. Give opioids preferably by the oral route and by the clock - short-acting opioids should be used to treat breakthrough pain. Alternatives are i.v. infusion, patient-controlled analgesia, and transdermal applications. Constipation is the adverse effect most often seen with (oral) opioid therapy. Adverse effects should be anticipated, and prophylactic treatment should be given consistently. The assistance of pediatric nurses is of the utmost importance in pediatric pain control. Nurses deliver the basis for rational and effective pain control by scoring pain intensity and documenting drug administration as well as adverse effects. The nurses' task is also to prepare the patient for and monitor the patient during painful procedures. It is the responsibility of both nurse and doctor to guarantee emergency intervention during sedation whenever needed. In our guideline we comment on drug selection and dosage, pain measurement tools, and documentation tools for the purpose of pain control. Those tools may be easily integrated into daily routine.
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PMID:[Practical pain control in pediatric oncology. Recommendations of the German Society of Pediatric Oncology and Hematology, the German Association for the Study of Pain, the German Society of Palliative Care, and the Vodafone Institute of Children's Pain Therapy and Palliative Care]. 1642 8

Mood and quality of life (QOL) outcomes vary widely in neuropathic pain trials. This may be a result of variable analgesia and other treatment effects. We evaluated the relationship between pain reduction and mood/QOL in neuropathic pain. Pain, side effects, QOL, and mood from a trial of morphine, gabapentin, and a morphine-gabapentin combination were examined. Baseline QOL was impaired according to Short Form Health Survey (SF-36) scores. Baseline mood, according to Profile of Mood States scores, was comparable to that of a nondepressed population. Pain reduction with all three active trial treatments correlated with improved QOL. Pain reduction with morphine and with gabapentin correlated with improved mood. Pain reduction with a morphine-gabapentin combination correlated with improvement in only one of several domains of the Profile of Mood States. Severity of sedation, constipation, and dry mouth during any treatment did not correlate with mood/QOL changes. These results can be interpreted to imply that larger analgesic treatment effect sizes lead to more substantial improvements in QOL and/or mood. However, other beneficial or adverse treatment-related side effects may also affect mood/QOL. Therefore, future studies are needed to also evaluate the impact of treatment-related side effects on mood/QOL in analgesic trials.
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PMID:The impact of therapy on quality of life and mood in neuropathic pain: what is the effect of pain reduction? 1663 29

Persistent pain represents a major quality-of-life burden for patients and a challenge for their physician. Chronic pain often arises from multiple tissue sources and involves multiple chemical mediators and pain transmission pathways. Successful long-term pain management requires analgesic regimens that can treat pains of multiple origin and type. Safety and tolerability are also a high priority when prescribing chronic therapy. Recent publications and regulatory developments affecting anti-inflammatory drugs have limited the options available for the management of chronic pain. Major concerns in long-term use of anti-inflammatory drugs include renal toxicity, gastrointestinal ulceration and bleeding and cardiovascular events, which can be of particular concern for elderly patients. Opioid agents avoid the end-organ toxicity seen with anti-inflammatory drugs, but their use may be limited, especially in the long term, by side effects such as constipation or sedation and by concerns about the potential for physical or psychological dependence. Paracetamol (acetaminophen) has a favourable safety and tolerability profile, although exceeding the recommended dose (up to 4 g/day) carries a risk of liver damage. It exerts simultaneous anti-nociception at both spinal and supra-spinal sites, and has shown self-synergy between these two routes of activity. Tramadol, an atypical weak opioid with a multi-modal mechanism of action, inhibits re-uptake of multiple neurotransmitters and has an improved safety and tolerability profile compared with traditional opioids. Rational combinations of analgesic drugs offer a viable approach to managing persistent pain that involves multiple sites or pathways. The combination of paracetamol plus tramadol brings together two well-known analgesics that have different but complementary mechanisms of analgesic action. Laboratory studies have demonstrated that these agents interact to produce synergistic analgesia with a desirable safety/efficacy profile.
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PMID:Pharmacological aspects of successful long-term analgesia. 1674 85

Development of analgesic tolerance and constipation remain a major clinical concern during long-term administration of morphine in pain management. Central endothelin mechanisms are involved in morphine analgesia and tolerance. The present study was conducted to investigate the effect of intracerebroventricular (i.c.v.) and peripheral administration of endothelin ET(A) receptor antagonist, BMS182874, and endothelin ET(B) receptor agonist, IRL1620, on morphine analgesia and changes in gastrointestinal transit in male Swiss Webster mice. Results indicate that morphine (6 mg/kg, s.c.) produced a significant increase in tail flick latency compared to control group. Pretreatment with BMS182874 (50 microg, i.c.v.) significantly enhanced morphine-induced analgesia, while IRL1620 (30 microg, i.c.v.) pretreatment did not affect tail-flick latency values. Changes in gastrointestinal transit were measured by percent of distance traveled by charcoal in the small intestine of gastrointestinal tract. Percent distance traveled in morphine (6 mg/kg, s.c.) treated mice (48.45+/-5.65%) was significantly lower (P<0.05) compared to control group (85.07+/-1.82%). Administration of BMS182874 centrally (50 mug, i.c.v.) or peripherally (10 mg/kg, i.p.) did not affect morphine-induced inhibition of gastrointestinal transit. Pretreatment with IRL1620 (30 microg, i.c.v., or 10 mg/kg, i.v.) also did not affect morphine-induced inhibition of gastrointestinal transit. This study demonstrates that endothelin ET(A) receptor antagonists delivered to the CNS enhance morphine analgesia without affecting gastrointestinal transit.
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PMID:Endothelin ETA receptor blockade potentiates morphine analgesia but does not affect gastrointestinal transit in mice. 1681 78

Opiate drugs, such as morphine, are renowned for their analgesic properties. To date, opioid narcotics represent the largest and most potent class of pain relievers available to treat both acute and chronic pain conditions. The use of opiates, however, is severely limited by several adverse side effects. Upon chronic use, opiates can produce tolerance, physical dependence and addiction. Although these conditions warrant consideration, there are acute effects that present more immediate concerns when choosing opiate narcotics for pain therapy. One of the most prevalent side effects, which continues for as long as the opiate is used for pain control, is constipation. This can impact patient compliance, as it is often one of the top reasons why patients discontinue opiate treatment. The challenge, therefore, is to develop pain therapies that preserve potent analgesia while preventing constipation.
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PMID:Opioid receptor signaling: relevance for gastrointestinal therapy. 1693 60

Opioid analgesics are the mainstay in the treatment of moderate-to-severe pain, yet their use is frequently associated with adverse effects, the most common and debilitating being constipation. Opioid-induced motor stasis results from blockade of gastrointestinal peristalsis and fluid secretion, and reflects the action of the endogenous opioid system in the gut. Methylnaltrexone and alvimopan are new investigational drugs that selectively target peripheral mu-opioid receptors because they are poorly absorbed in the intestine and do not enter the brain. Clinical studies have proved the concept that these drugs prevent opioid-induced bowel dysfunction without interfering with analgesia. As reviewed in this article, opioid receptor antagonists with a peripherally restricted site of action also hold therapeutic promise in postoperative ileus and chronic constipation due to the fact that they have been found to stimulate intestinal transit.
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PMID:Treatment of opioid-induced gut dysfunction. 1724 38


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