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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer pain remains a worldwide problem and some patients continue to be undermedicated because of concerns about tolerance and drug dependence. The aim of this study was to document the morphine intake of patients with chronic cancer pain in an inpatient palliative care unit and to describe the long-term pattern of morphine use and pain intensity in this patient population. With IRB approval and written informed consent, patients admitted over a 64-week period to the palliative care unit at the Royal Victoria Hospital, Montreal, were candidates for this study. Cancer patients receiving morphine for 30 days or longer who were able to complete the pain scale were included. Excluded were patients with a confused or clouded sensorium. Daily pain intensity was recorded by the PPI (0-5 scale) of the McGill pain questionnaire. The daily morphine consumption was recorded and the occurrence and intensity of breakthrough pain were also recorded. Of the 35 potential candidates for study, 17 patients with a mean age of 59 (14) years completed the study. Patients were followed up for a mean of 82 (52) days. The mean (S.D.) daily morphine dosage at study entry was 135 (127) mg, and the daily morphine dose at study completion was 244 (240) mg. There was no evidence that any patient rapidly developed tolerance to morphine. Pain was well controlled for most patients. For 10 of 17 patients, 93% reported PPI scores of either 0 or 1. Occasional breakthrough pain was experienced by 4 of these 10 patients. Four other patients reported 79% of their PPI scores as either 0 or 1, and 18% of the PPI scores as either 2 (discomforting) or 3 (disturbing), Thus 82% of patients had good to excellent pain control. Three of 17 patients spent more than four months in the unit and had less than good pain control. All of these patients had neuropathic cancer pain. These results support the conclusion that pain was well controlled for most cancer patients, and that increases in daily morphine dose, when it occurred, generally developed over a period of weeks to months, and a pattern of rapid escalation in morphine dose did not occur.
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PMID:Long-term patterns of morphine dosage and pain intensity among cancer patients. 1062 31

The role of the opioid system in controlling pain, reward and addiction is well established, but its role in regulating other emotional responses is poorly documented in pharmacology. The mu-, delta- and kappa- opioid receptors (encoded by Oprm, Oprd1 and Oprk1, respectively) mediate the biological activity of opioids. We have generated Oprd1-deficient mice and compared the behavioural responses of mice lacking Oprd1, Oprm (ref. 6) and Oprk1 (ref. 7) in several models of anxiety and depression. Our data show no detectable phenotype in Oprk1-/- mutants, suggesting that kappa-receptors do not have a role in this aspect of opioid function; opposing phenotypes in Oprm-/- and Oprd1-/- mutants which contrasts with the classical notion of similar activities of mu- and delta-receptors; and consistent anxiogenic- and depressive-like responses in Oprd1-/- mice, indicating that delta-receptor activity contributes to improvement of mood states. We conclude that the Oprd1-encoded receptor, which has been proposed to be a promising target for the clinical management of pain, should also be considered in the treatment of drug addiction and other mood-related disorders.
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PMID:Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. 1083 36

Pentazocine and cyclazocine are two benzomorphans that were synthesized by the late Sydney Archer in 1962. These benzomorphans were synthesized as part of an effort to develop analgesics with little or no abuse potential. Pentazocine is used as an analgesic, often in individuals who have sever pain or in those who have drug-abuse problems. Cyclazocine is a low-liability analgesic and potential therapeutic for the treatment of drug abuse. The risk of drug dependence is lower with the benzomorphans, which usually act as partial agonists at the mu opioid receptor and as kappa agonists. In an attempt to synthesize analogs of cyclazocine with increased bioavailability and varying kappa agonist and partial mu agonist properties, a series of 8-amino derivatives of cyclazocine were synthesized. These compounds were characterized in radioligand binding assays for their affinity and selectivity for the mu, delta, and kappa opioid receptors. Mouse antinociceptive tests were used to characterize the agonist and antagonist properties of each compound at the mu, delta and kappa receptors.
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PMID:Partial opioids. Medications for the treatment of pain and drug abuse. 1091 20

Long-term administration of morphine for chronic non-malignant pain continues to be controversial, mainly because of the fear of opioid addiction and abuse. It is important to distinguish three phenomena: tolerance of the analgesic and side-effects of the drug, physical dependence (which is a pure pharmacological event) and addiction (defined as a compulsive drug-related behaviour). Animal studies suggest that similar mechanisms underlie tolerance and physical dependence. These may result from an imbalance between anti- and pro-nociceptive mechanisms. By contrast, the occurrence of an addictive behaviour depends on both different endogenous mechanisms and environmental factors. Clinical data suggest that the use of stable doses of morphine (or other opiates) is common in patients suffering from chronic non-malignant pain. However, drug addiction might develop in 'at-risk patients' and therefore the decision to start long-term treatment with an opiate should be undertaken very cautiously, and ongoing assessment of aberrant drug-related behaviours should be undertaken repeatedly.
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PMID:[Tolerance and dependence on opioid analgesics: experimental and clinical aspects]. 1096 10

The World Health Organization (WHO) developed practical guidelines for pain relief in cancer patients in 1986. Although morphine is a standard opioid analgesic with sufficient analgesic potency, it also has undesirable effects such as drug dependence. Considering the significant of the management of patients with chronic cancer pain, it is no exaggeration to say that the investigation of morphine dependence is now most required research for pain relief. Various studies provide arguments to support substantial roles for mu-opioid receptors associated with the mesolimbic dopaminergic pathway and the possible involvement of delta-opioid receptors in the rewarding effect by morphine in animals. By contrast, the activation of kappa-opioid receptors leads to the suppression of this effect of morphine. It is noteworthy that chronic inflammatory nociception enhances endogenous kappa-opioidergic system, leading to the suppression of rewarding effects of morphine. These results obtained from the basic research strongly reflect the clinical results that psychological dependence on morphine is not a major concern when morphine is used to control pain for cancer patients. Another limiting factor in the clinical utilization of opioids is that repeated administration leads to the development of tolerance to opioids. At the cellular level, phosphorylation of opioid receptors by protein kinases, especially G-protein-coupled receptor kinase (GRK) and protein kinase C (PKC), is likely to play a major role in these tolerant and dependent states. We recently found that repeated administration of mu-agonist causes a down regulation of mu-receptor-mediated G-protein activation, which is associated with a specific upregulation of PKC gamma isoform. We therefore propose that PKC gamma may play a critical role in the development of morphine tolerance.
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PMID:[A new turn of research for morphine dependence]. 1114 49

Acupuncture, a therapeutic Chinese practice, may reduce fever, activate the immune system, and stimulate white blood cells. Scientists feel acupuncture encourages the production of natural hormones, called endorphins, which reduce pain, promote sleep and regulate body systems. Endorphins can be produced by massages, acupuncture and the body's natural activity. Medicinal plants, herbs, vitamins and minerals help the body maintain a healthy balance. Acupuncture is done with tiny sterile needles, placed painlessly in the skin and left there from several seconds to almost an hour. AIDS patients who experience pain, coughing, weight loss, or gland inflammation respond well to acupuncture and herbal medications. The Chinese believe that people with sleeping problems or depression have a lack of equilibrium of the heart. An acupuncturist would treat the heart with points near the wrist and ear. This treatment also assists alcohol and drug addiction, improving health and reducing the desire for the drug.
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PMID:[Chinese medicine and acupuncture in the treatment of AIDS]. 1136 71

Activity-dependent changes in gene expression involving the transcription factor cAMP-response element-binding protein (CREB) occur in learning and memory, pain, and drug addiction. This mechanism may also be important for cytomegaloviral infections of the brain. The human cytomegalovirus major immediate-early promoter/enhancer (hCMV promoter), rate-limiting for productive cytomegalovirus infection, contains five cAMP-response elements (CREs). Indirect evidence suggests that this promoter does not function in unstimulated neurons. Here we test the hypothesis that expression from the hCMV promoter in neurons is induced by membrane depolarization. For these experiments, we infected cultured sympathetic and hippocampal neurons with hCMV-green fluorescent protein (GFP) promoter/reporter constructs using adenoviral gene transfer techniques and measured transgene expression by quantifying GFP fluorescence and GFP mRNA levels. We found that depolarization up-regulates promoter activity by >90-fold. Moreover, our results from pharmacological experiments suggest that this induction occurred through a CREB-dependent pathway. Importantly, site-directed mutagenesis of all five CREs in the promoter blocked this up-regulation almost completely, whereas mutating four of them had no effect. We conclude that the hCMV promoter acts as a molecular switch in neurons and is strongly induced by membrane depolarization, neuronal activity, or other stimuli that activate CREB. These results may provide insight into molecular mechanisms of cytomegalovirus-related diseases of the brain.
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PMID:Depolarization strongly induces human cytomegalovirus major immediate-early promoter/enhancer activity in neurons. 1139 4

The recent cloning of two GABA(B) receptor subunits, GABA(B1) and GABA(B2), has raised the possibility that differences in GABA(B) receptor subunit composition may give rise to pharmacologically or functionally distinct receptors. If present, such molecular diversity could permit the selective targeting of GABA(B) receptor subtypes specifically involved in pathologies such as drug addiction, spasticity, pain, and epilepsy. To address these issues we have developed a GABA(B1) subunit knockout mouse using gene targeting techniques. In the brains of GABA(B1) null mice, all pre- and postsynaptic GABA(B) receptor function was absent demonstrating that the GABA(B1) subunit is essential for all GABA(B) receptor-mediated mechanisms. Despite this, GABA(B1) null mice appeared normal at birth, although by postnatal week four their growth was retarded and they developed a generalized epilepsy that resulted in premature death. In addition, GABA(B1) heterozygote animals showed enhanced prepulse inhibition responses compared to littermate controls, suggesting that GABA(B1) deficient mice exhibit increased sensorimotor gating mechanisms. These data suggest that GABA(B) receptor antagonists may be of benefit in the treatment of psychiatric and neurological disorders in which attentional processing is impaired.
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PMID:Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. 1141 94

A CHALLENGING SITUATION: A number of patients experiencing chronic noncancer pain are unsatisfied with standard treatment modalities. This raises the question of whether there may be a place for strong opioids in the management of these patients. Randomised placebo-controlled trials of strong opioids generated rather disappointing results in this type of pain. Observational studies have indicated that strong opioids may improve comfort and function in some patients with intractable nociceptive or neuropathic pain. However, opioids may be ineffective in others and intolerable side effects, heightened pain and functional impairment as well as drug addiction may also occur. A PROMISING SOLUTION: Finally, strong opioids do not appear to be the issue to all intractable chronic nonmalignant pain states, but they may be a possible issue to a subset of selected and informed patients who agree on the goals of the treatment and accept regular monitoring.
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PMID:[Strong opioids for chronic non-cancer pain]. 1143 25

Nociceptin, a neuropeptide 17 amino acid residues in length, is the first novel bioactive substance to have been discovered by functional genomics. Nociceptin was isolated from a rat brain extract as the endogenous ligand to an orphan receptor, ORL1 (Opioid Receptor-Like 1), structurally akin to opioid receptors, whose cDNA had been cloned from a human brain stem library. The peptide is processed from a larger precursor polypeptide, prepro-nociceptin, which is widely distributed in the nervous system. Nociceptin is primarily an inhibitory neuropeptide that acts on neurons to depress synaptic transmission. Nociceptin's wide spectrum of pharmacological actions hints at several potential therapeutic applications for ORL1 receptor agonists and/or antagonists, particularly for treating pain states, stress and anxiety, cognitive defects, and drug addiction. A major challenge is now the discovery and pharmacological in vivo profiling of ORL1 receptor ligands that are active by medically practical routes of administration.
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PMID:[Fom orphan receptor to novel neuropeptide: an example of reverse pharmacology]. 1147 99


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