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

Effective management of chronic pain has become an increasingly critical issue in health care. Opioid agonists are among the most effective analgesics available for reducing pain perception; however, their chronic use is controversial. This is primarily due to regulatory barriers, misunderstandings about pain management among primary caregivers, fear of adverse side effects, and misconceptions about the potential risks of addiction. Short-acting opioids provide effective analgesia for acute pain but should be avoided as primary analgesics for chronic pain management. Long-acting opioids have greater utility than short-acting opioids in treating chronic pain in patients with consistent pain levels. Results of studies show that improved quality of life is directly related to the use of long-acting opioids in patients with chronic pain of both cancer and noncancer etiology. Short-acting opioids may be used during the initial dose titration period of long-acting formulations and as rescue medication for episodes of breakthrough pain. Clinical experience reveals that selection of an effective pain regimen for the patient with chronic pain, combined with aggressive management of side effects, leads to improved overall functioning and quality of life.
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PMID:Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia. 1134 85

Children frequently received no treatment, or inadequate treatment, for pain and for painful procedures. The newborn and critically ill children are especially vulnerable to no treatment or under-treatment. Nerve pathways essential for the transmission and perception of pain are present and functioning by 24 weeks of gestation. The failure to provide analgesia for pain results in rewiring the nerve pathways responsible for pain transmission in the dorsal horn of the spinal cord and results in increased pain perception for future painful results. Many children would withdraw or deny their pain in an attempt to avoid yet another terrifying and painful experiences, such as the intramuscular injections. Societal fears of opioid addiction and lack of advocacy are also causal factors in the under-treatment of pediatric pain. False beliefs about addictions and proper use of acetaminophen and other analgesics resulted in the failure to provide analgesia to children. All children even the newborn and critically ill require analgesia for pain and painful procedures. Unbelieved pain interferes with sleep, leads to fatigue and a sense of helplessness, and may result in increased morbidity or mortality.
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PMID:Pain management in the critically ill child. 1156 53

The nucleus accumbens, as part of the mesolimbic dopaminergic reward pathway, mediates both addiction to and withdrawal from substances of abuse. In addition, activity of substances of abuse such as opioids in the nucleus accumbens has been implicated in pain modulation. Because nucleus accumbens nicotinic receptors are important in nicotine addiction and because nicotinic activity can interact with opioid action, we investigated the contribution of nucleus accumbens nicotinic receptors to opioid-mediated analgesia/antinociception. The response of the nociceptive jaw-opening reflex to opioids was studied in the rat, both before and during chronic nicotine exposure. In nicotine-naive rats, intra-accumbens injection of the nicotinic receptor antagonist mecamylamine blocked antinociception produced by either systemic morphine, intra-accumbens co-administration of a mu- and a delta-opioid receptor agonist, or noxious stimulation (i.e., subdermal capsaicin in the hindpaw); intra-accumbens mecamylamine alone had no effect. The antinociceptive effect of either morphine or noxious stimulation was unchanged during nicotine tolerance; however, intra-accumbens mecamylamine lost its ability to block antinociception produced by either treatment. Intra-accumbens mecamylamine by itself precipitated significant hyperalgesia in nicotine-tolerant rats which could be suppressed by noxious stimulation as well as by morphine. These results indicate that nucleus accumbens nicotinic receptors play an important role in both opioid- and noxious stimulus-induced antinociception in nicotine-naive rats. This role was attenuated in the nicotine-dependent state. The suppression of withdrawal hyperalgesia by noxious stimulation suggests that pain can ameliorate the symptoms of withdrawal, thus suggesting a possible mechanism for pain-seeking behavior.
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PMID:Nicotine withdrawal hyperalgesia and opioid-mediated analgesia depend on nicotine receptors in nucleus accumbens. 1156 23

Alvimopan (ADL 8-2698; Adolor Corporation, Exton, PA, USA) is a novel, peripherally restricted opioid antagonist. After oral administration, it has activity specific to the gastrointestinal (GI) tract. ADL 8-2698 has low systemic absorption and a high affinity for mu-opioid receptors. In healthy subjects, ADL 8-2698 antagonized loperamide-induced changes in GI transit and prevented morphine-induced delays in oral-cecal transit time without antagonizing centrally mediated opioid effects, such as analgesia or pupillary constriction. In the treatment of opioid naive patients who underwent surgery and received opioids for acute pain, oral ADL 8-2698 (6.0 mg) improved the management of postoperative ileus (POI) by shortening the time to achieve normal bowel function and, ultimately, hospital stay. Postoperative nausea and vomiting and the overall incidence of all GI side effects were reduced in patients treated with ADL 8-2698 for POI. Analgesia was not compromised, because there were no changes in median opioid consumption or Visual Analog Scale (VAS) pain scores in patients treated with ADL 8-2698 versus patients treated with placebo. No drug-related side effects were observed in acute pain postsurgical patients in the initial POI study. In patients treated with opioids for chronic pain or opioid addiction, lower doses of oral ADL 8-2698 (0.5 to 3.0 mg) reversed opioid bowel dysfunction (OBD) and normalized GI activity. These effects were evident without compromising opioid analgesia or inducing central nervous system symptoms of withdrawal. Some chronic opioid patients receiving apparently supramaximal doses of ADL 8-2698 (> or = 3.0 mg) reported localized GI side effects, possibly indicative of a localized GI withdrawal response. The most common side effects of ADL 8-2698 in chronic pain patients with OBD were abdominal pain, flatulence, and diarrhea. These effects were not observed in most OBD patients receiving lower doses of ADL 8-2698. Overall, ADL 8-2698 was well tolerated in clinical trials. Further studies to evaluate the efficacy and safety of ADL 8-2698 in clinical practice are in progress.
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PMID:Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist. 1175 94

The mu opioid receptor (MOR) is thought to mediate a variety of morphine's effects, including analgesia and addiction. The expression of opioid receptors can be up and down regulated, but little is known about molecular processes that regulate expression of the MOR gene. To study the regulatory elements that control expression of the human MOR (hMOR) gene, 2325 bp of the 5'-regulatory sequence of the hMOR gene were cloned and sequenced. A transcription initiation site (TIS) was mapped 252 (-252) nucleotides upstream from the translation start site (+1) by primer extension experiments using human thalamus poly(A)+ mRNA. In addition, several putative distal TISs were also identified; the most distal site was mapped 663 bp upstream of the translation start site. A series of 5'-deleted hMOR promoter-luciferase constructs were made and transiently transfected into a MOR expressing neuroblastoma cell line, SK-N-SH, and a non-expressing cell line, HeLa. These transient transfection studies indicated that the region from -563 to -292 contained a strong enhancer element(s), while the region from -776 to -564 possessed a repressor element(s). A similar transfection pattern was observed with SK-N-SH and HeLa cells, suggesting that there is not a tissue-specific element in the region from -2325 to -252.
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PMID:Functional characterization of the promoter region of the human mu opioid receptor (hMOR) gene: identification of activating and inhibitory regions. 1193 71

The endogenous opioid system consists of three opioid peptide precursor genes encoding enkephalins (preproenkephalin, Penk), dynorphins (preprodynorphin, Pdyn) and beta-endorphin (betaend), proopiomelanocortin (POMC) and three receptor genes encoding mu-opiod receptor (MOR), delta-opiod receptor (DOR) and kappa-opiod receptor (KOR). In the past years, all six genes have been inactivated in mice by homologous recombination. The analysis of spontaneous behavior in mutant mice has demonstrated significant and distinct roles of each gene in modulating locomotion, pain perception and emotional behaviors. The observation of opposing phenotypes of MOR- and DOR-deficient mice in several behaviors highlights unexpected roles for DOR to be further explored genetically and using more specific delta compounds. The analysis of responses of mutant mice to exogenous opiates has definitely clarified the essential role of MOR in both morphine analgesia and addiction, and demonstrated that DOR and KOR remain promising targets for pain treatment. These studies also show that prototypic DOR agonists partially require MOR for their biological activity and provide some support for the postulated mu-delta interactions in vivo. Finally, data confirm and define a role for several genes of the opioid system in responses to other drugs of abuse, and the triple opioid receptor knockout mutant allows exploring non-classical opioid pharmacology. In summary, the study of null mutant mice has extended our previous knowledge of the opioid system by identifying the molecular players in opioid pharmacology and physiology. Future studies should involve parallel behavioral analysis of mice lacking receptors and peptides and will benefit from more sophisticated gene targeting approaches, including site-directed and anatomically-restricted mutations.
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PMID:Exploring the opioid system by gene knockout. 1201 97

Administration of opioids to alleviate moderate to severe acute pain and chronic cancer pain is an established management process. However, advancements in clinical pharmacologic research have shown that opioids are also effective in chronic noncancerous pain. Many patients properly treated for prolonged periods with opioids develop tolerance and subsequently, physical dependence. This process is not necessarily harmful to the patient and will not cause the patient to develop an addiction (properly defined as psychologic dependence). For many patients who have been on opioid therapy for months or years, analgesic effectiveness tragically becomes less. In addition, opioid-induced constipation can be severe and cause pain; patients do not develop tolerance to this adverse reaction. Therefore, such issues become a management problem and require additional intervention. Currently, many different classes of drugs can serve as effective adjuncts to opioids for treatment of pain. Adding adjunctive medication to opioid therapy improves pain management primarily by nonopioid mechanisms of action. Clinical outcomes of such combinations include greater analgesia and attenuation of opioid-induced adverse reactions such as nausea and vomiting, constipation, sedation, and respiratory depression. Adjuncts include acetaminophen, antiarrhythmics, anticonvulsants, antidepressants, antipsychotics, baclofen, benzodiazepines, capsaicin, calcium channel blockers, clonidine hydrochloride, central nervous system stimulants, corticosteroids, local anesthetics, N-methyl-D-aspartate receptor antagonists, nonsteroidal antiinflammatory drugs, pentoxifylline, and scopolamine. Some adjuncts (eg, acetaminophen) are routinely used today, whereas others (eg, nifedipine [calcium channel blocker]) are used on a limited basis but have great potential for more widespread application. All professionals (eg, nurses, pharmacists, physicians, physicians' assistants, social workers, members of the clergy) involved in treating patients with unresolved pain recognize this to be an extraordinary and delicate time. It is when patients are likely to request physicians to provide some method to accelerate their death. Thus, inadequate analgesia can become a suicidogen, ie, any factor that causes a patient to want to commit suicide. Incorporation of adjuncts to opioid therapy can serve to lessen pain and improve quality of life for a suffering patient.
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PMID:Adjuncts to opioid therapy. 1235 36

In contrast to other opioids, fentanyl and buprenorphine share a number of physicochemical properties that render both agents potentially suitable for transdermal delivery. However, there are significant differences between them in terms of their pharmacological profiles, as fentanyl is a full mu opioid receptor agonist capable of exerting a maximal response in certain tissues, while buprenorphine is a partial agonist unable to exert this maximum effect even at high doses. This review examines the hypothesis that partial opioid agonists would confer a number of benefits over full agonists, namely effective analgesia with a better tolerability and a lower propensity for addiction, with respect to fentanyl and buprenorphine. An attempt is also made to correlate clinical differences between these drugs with their respective agonist profiles and other differential pharmacokinetic/pharmacodynamic properties. Despite a dearth of directly comparative trials, the pharmacology of fentanyl and buprenorphine is well documented. Considerable data concerning buprenorphine suggest that the advantages initially espoused for partial opioid agonists are not borne out in clinical practice. Indeed, it may be postulated that full mu opioid agonists, particularly those with high selectivity and potency such as fentanyl, have a superior clinical profile and fulfill the above criteria more closely. Relative receptor binding, selectivity, potency and intrinsic efficacy of the opioids appear to be key determinants of their individual pharmacological profiles, contributing significantly to the heterogeneity of this class of analgesics.
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PMID:Partial versus full agonists for opioid-mediated analgesia--focus on fentanyl and buprenorphine. 1246 29

The identification of the disease of addiction is important to safe and effective clinical management of pain in persons with addictive disorders. The disease of addiction affects approximately 10% of the general population, and its prevalence may be higher in subpopulations of patients with pain. The presence of active addiction may facilitate the experience of pain. Both active and recovering addiction may complicate the use of medications, such as opioids, important to the management of pain. There is, further, persistent misunderstanding among health care providers, regulators, and the general population regarding the nature and manifestations of addiction that may result in undertreatment of pain and stigmatization of patients using opioids for pain control. The author seeks to clarify understanding of addiction, to underscore the importance of identifying addiction in the context of pain treatment, and to provide a rational approach to assessment for addiction in patients with pain. Current scientific understanding of addiction as a chronic illness is briefly reviewed. Recent definitions related to addiction are presented. The impact of addictive disorders on pain and pain treatment are explored. The roles of medical interview, physical examination, laboratory studies, and standard addiction screening tools in assessing for addiction are outlined. Differential considerations in distinguishing therapeutic use of opioids for analgesia from addictive or other nontherapeutic use of opioids are discussed. In summary, the article provides salient background and a detailed approach to assessment for addictive disorders in the context of pain treatment.
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PMID:Assessment for addiction in pain-treatment settings. 1247 52

Dihydroetorphine (DHE) is one of the strongest analgesic opioid alkaloids known; it is 1000 to 12000 times more potent than morphine. Several in vitro and in vivo studies have shown that DHE is a selective mu-opioid receptor (OP(3)) agonist that also binds and activates all human recombinant mu-, delta-, and kappa-opioid receptors (OP(3), OP(1), and OP(2)). The onset of the analgesic effect of DHE in rodents is rapid, 5 to 15 min after parenteral administration; the duration of action is short, the analgesic effect disappears within 120 min after administration. By oral administration much higher doses of DHE are required to produce analgesic effects. These characteristics are accounted for by the pharmacokinetic properties of DHE in the rat, namely, by rapid distribution of DHE from the injection site to the brain and rapid metabolism by glucuronidation in the gut and liver followed by elimination into the bile. Continuous infusion and repeated administration of DHE lead to the development of tolerance to analgesia, physical dependence, and a rewarding effect in normal rats but not in animals with formalin-induced inflammation. Although formalin-induced inflammation is only one type of pain stimulus, these findings suggest that DHE addiction would be observed only in the case of pain-free conditions. Clinical reports in China show that sublingual doses of DHE, 20 to 180 microg, produce a potent analgesic effect with only mild side effects, including dizziness, somnolence, nausea, vomiting, constipation, and shortness of breath. To improve the short-lasting effect following sublingual administration, transdermal delivery of DHE via a patch has been investigated. The patch formulation of DHE produces continuous analgesic effect with minimal physical dependence and rewarding effect in rats suffering from chronic pain. This patch formulation, which is very suitable for DHE, may be viable for the treatment of severe pain and is likely to improve patients' quality of life.
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PMID:Dihydroetorphine: a potent analgesic: pharmacology, toxicology, pharmacokinetics, and clinical effects. 1248 Nov 94


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