Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mu opioid receptor (MOR), the primary binding site for morphine, is an important target for treating pain and drug addiction. The MOR gene is tightly regulated at the level of transcription, and potential polymorphisms in its 5' regulatory region can cause individual variation in MOR gene expression, nociception, and opiate responses. To study the 5' regulatory region of the human MOR gene (hMOR), we further investigated our previous finding of two regulatory regions and have localized a 40-bp positive cis-acting element and a 35-bp negative cis-acting element that regulate hMOR transcription in SK-N-SH cells. Electromobility shift assays and methylation interference assay with the 40-bp probe suggested that protein contacts were made with the core recognition sequence GCC (-510 to -508). The 35-bp sequence (-694 to -660) was the hMOR homolog of the mMOR negative regulatory element, and it suppressed proximal promoter activity of the hMOR gene. Additionally, the presence of an hMOR distal promoter was confirmed using RT-PCR. However, the activity of the distal promoter construct (-2325 to -777) was weak compared with the activity of the proximal promoter construct (-776 to -212).
 ...
PMID:Transcriptional regulation of the human mu opioid receptor (hMOR) gene: evidence of positive and negative cis-acting elements in the proximal promoter and presence of a distal promoter. 1150 3

Pain is the main symptom and the major indication for surgery in a large proportion of patients with chronic pancreatitis. Since the characters of pain (including frequency, severity, duration and cause) differ among the patients with chronic pancreatitis, their management remains a difficult and challenging problem. Initial treatment is always conservative and may require a multidisciplinary approach involving gastroenterologist, anesthesiologist, psychologist for chemical addiction (alcohol and/or narcotics), and surgeon. When non-operative management fails to achieve pain relief and pain markedly alters quality of life, surgery should be considered. A thorough knowledge of the pathophysiology of pain offers the theoretical basis for both conservative and surgical treatment of chronic pancreatitis. The selection of the surgical procedure should be based on the structural changes of the pancreas.
 ...
PMID:Pathophysiology of pain in chronic pancreatitis: clinical implications from a surgical perspective. 1158 94

Chemical dependence constitutes a significant public health problem with immeasurable physical and psychological sequelae. Pain management is generally undertreated in this population because of the associated stigma and misconceptions about both pain and chemical dependence. The plan of care in the perioperative period is complicated by the increased incidence of related trauma, medical and psychiatric problems, and the risk for withdrawal. An overview of assessment, anesthetic considerations, pain management, postoperative care, and treatment modalities for chemical dependence is presented in this article. Perianesthesia nurses need to become competent and confident when caringfor this population by increasing their knowledge base and confronting long-held myths and biases. Adherence to established standards of care will help to promote clinician accountability and quality patient care.
 ...
PMID:Perioperative pain management in the chemically dependent patient. 1181 35

Stimulation of the brain CCK2 receptor by the C-terminal octapeptide CCK8 of cholecystokinin (CCK) negatively modulates opioid responses. This suggests the existence of physiologically relevant interactions between endogenous CCK and opioid peptides, opening new perspectives particularly in the treatment of pain or drug addiction. CCK2 receptor-deficient mice were used to analyze the incidence of this gene invalidation on opioid system. Compared with wild-type mice, mutants exhibited the following: (1) a hypersensitivity to the locomotor activity induced by inhibitors of enkephalin catabolism or by morphine; (2) a spontaneous hyperalgesia to thermal nociceptive stimulus, which was reversed by previous administration of the NMDA antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], and a large reduction in analgesic effects of endogenous or exogenous opioids; and (3) a more severe withdrawal syndrome after chronic morphine treatment. As expected, stimulation of mu, delta, and D2 receptors on brain tissue of wild-type animals induced a dose-dependent decrease in adenylate cyclase activity, whereas a striking mirror effect was observed in mutants. All of these results suggest that the absence, in knock-out mice, of the negative feedback control on the opioid system, normally performed out by CCK2 receptor stimulation, results in an upregulation of this system. These biochemical and pharmacological results demonstrate the critical role played by CCK2 receptors in opioid-dependent responses.
 ...
PMID:Deletion of CCK2 receptor in mice results in an upregulation of the endogenous opioid system. 1188 May 31

Opioid receptors (OR) are involved in many physiological and pathological immune functions. During recent years, the treatment of opiate addiction with methadone in HIV-positive and HIV-negative patients has become widely accepted. However, little is known on the occurrence and course of OR on lymphocytes of these individuals. The objective of the study was to detect and quantify OR on peripheral white blood cells (WBC) by fluorescence-activated cell sorting using polyclonal antibodies and reverse transcriptase polymerase chain reaction, and to assess the influence of HIV infection and methadone treatment. We compared OR levels in 80 HIV-positive homosexuals, 18 HIV-positive intravenous drug users (IVDU) treated with methadone, 18 HIV-negative IVDU receiving methadone and 25 healthy controls. HIV infection was shown to decrease the amount of OR on WBC, especially of the delta-subtype on lymphocytes and granulocytes. The decrease correlated with the duration of HIV-infection (P<0.01), and inversely with the HIV viral load (P<0.01). In contrast, chronic methadone administration led to a significant increase of OR exclusively in HIV-negative IVDU. In particular the delta-OR was increased by 31-, 62- and 42-fold on lymphocytes, monocytes and granulocytes of HIV-negative patients (each P<0.005), respectively, which was not observed in HIV-positive IVDU. Therefore, HIV seems to reduce OR particularly on lymphocytes and granulocytes regardless of the mode of HIV transmission. The quantification of OR on immune cells may help to elucidate the effects of opioid analogues in health and drug addiction.
Pain 2002 Jul
PMID:Opioid receptors on white blood cells: effect of HIV infection and methadone treatment. 1209 31

International requirements for central nervous system (CNS) safety pharmacology are reviewed. Procedures for initial CNS safety screening (core battery studies) can be conducted from the beginning of the drug discovery process, but at latest before first studies in man. They should include assessment of general behaviour, locomotor activity and motor coordination, but can also include studies of pain sensitivity, convulsive threshold and interaction with hypnotics. Follow-up studies, to be conducted later in the drug development process but before product approval, cover assessment of higher cognitive function, electroencephalogram (EEG) and drug dependence/abuse liability. Procedures for assessing cognitive function can include, in order of complexity, passive avoidance, Morris and radial mazes and operant behaviour tasks (delayed alternation, repeated acquisition). EEG can include the quantified EEG (QEEG) and studies of the sleep/wakefulness cycle. Drug dependence/abuse procedures can include precipitated and nonprecipitated withdrawal (drug dependence), and place preference, drug discrimination and self-administration (drug abuse). In contrast to core battery CNS procedures, conducted exclusively in rodents, follow-up studies can include higher species, in particular primates.
 ...
PMID:New perspectives in CNS safety pharmacology. 1216 67

Overall, it is apparent that opioids do affect host defense mechanisms. Heroin users present with an altered and functionally impaired immune system and have a higher prevalence of infectious diseases than do nonaddicts. Individuals exposed to opioid treatment for pain management during surgical procedures or maintained on oral methadone for treatment of drug addiction show either no effect or a suppressed immune system, depending on dosage and, in the case of methadone-maintained patients, duration of drug treatment. Confounding factors in these studies undermine definitive conclusions about the mechanisms by which opioids induce their immunomodulatory effects. Animal models have provided the means by which investigators can study the effects of opioids in a complex, biologic system that is easily manipulated and controlled. Findings from these studies have confirmed human data associating a pathogenic susceptibility with opioid use. Animal models have shown the complexity of this association. Interaction of the CNS, the autonomic nervous system, and the HPA axis is required for the varied effects of opioids on the immune system. By implication, exogenous opioids may be mimicking pathways by which endogenous opioids are involved in regulating immune defenses. To minimize the increased incidence of infectious diseases in heroin users and individuals clinically exposed to opioids, it will be important to determine the individual and collective effects of the opioid-induced activation of these pathways and the consequences of that activation to the immune system.
 ...
PMID:Opioids, immunology, and host defenses of intravenous drug abusers. 1237 Nov 15

Neuropeptide Y (NPY) is a 36-amino-acid peptide that exhibits a large number of physiological activities in the central and peripheral nervous systems. NPY mediates its effects through the activation of six G-protein-coupled receptor subtypes named Y(1), Y(2), Y(3), Y(4), Y(5), and y(6). Evidence suggests that NPY is involved in the pathophysiology of several disorders, such as the control of food intake, metabolic disorders, anxiety, seizures, memory, circadian rhythm, drug addiction, pain, cardiovascular diseases, rhinitis, and endothelial cell dysfunctions. The synthesis of agonists and antagonists for these receptors could be useful to treat several of these diseases.
 ...
PMID:Neuropeptide Y and its receptors as potential therapeutic drug targets. 1241 94

This position paper from the College on Problems of Drug Dependence addresses the issues related to non-medical use and abuse of prescription opioids. A central theme throughout is the need to strike a balance between risk management strategies to prevent and deter prescription opioid abuse and the need for physicians and patients to have appropriate access to opioid pharmaceuticals for the treatment of pain. The epidemiology of prescription opioid use and abuse is reviewed. Non-medical use and abuse of prescription opioids are on the rise in the United States, illicit use of several widely prescribed opioids has increased disproportionately more than illicit use, and the prevalence of prescription opioid abuse appears to be similar to that of heroin and cocaine abuse. There is a paucity of abuse liability testing of prescription opioids, and methods should be developed to fill critical gaps in our knowledge in this area. The role of regulatory agencies in preventing diversion of prescription opioids and identifying potential sources of diversion are discussed. More research is needed to identify those populations most at risk for abusing prescription opioids, and then to develop appropriately targeted prevention programs. Treatment options are discussed; these depend on whether or not an abuser is in pain. Prescription opioid abuse has harmful ramifications for the legitimate and appropriate use of opioids, including stigmatization, opiophobia, and undertreatment of pain. Recommended steps to take include further epidemiological research, laboratory testing of prescription opioids to determine abuse liability, and clinical trials to determine the efficacy of different approaches to the prevention and treatment of prescription opioid abuse.
 ...
PMID:College on Problems of Drug Dependence taskforce on prescription opioid non-medical use and abuse: position statement. 1263 8

Heroin treatment or abusive drug addiction influences many physiological functions, including the reactions of the immune system. Although suppression of various manifestations of the immune system after heroin (or morphine) administration has been reported, we show here that production of proinflammatory cytokines and nitric oxide (NO) was enhanced and allotransplantation reactions were accelerated significantly in heroin-treated recipients. Mice were treated by a subcutaneous administration of heroin (diacetylmorphine) given in one or repeated daily doses. The ability of spleen cells from treated mice to respond in vitro to alloantigens and to produce IL-2, IL-4, IL-10 and IFN-gamma, and the production of IL-1beta, IL-12 and NO by peritoneal macrophages, were tested. Within 2 h after heroin administration, proliferative responses to alloantigens and the production of IL-1beta, IFN-gamma, IL-12 and NO were enhanced significantly. In contrast, the production of anti-inflammatory cytokines IL-4 and IL-10 was at the same time rather decreased. As a consequence, skin allografts in heroin-treated mice were rejected more promptly than in untreated or vehicle-treated recipients. Similarly, the growth of allogeneic tumours induced by high doses of tumour cells was suppressed significantly in heroin-treated mice. The enhancing effects of heroin on the production of proinflammatory cytokines were antagonized by naltrexone, a specific inhibitor of classic opioid receptors. These results show that heroin treatment augments production of proinflammatory cytokines and accelerates allotransplantation reactions. The observations thus illustrate the complexity of the effects of heroin on the immune system and should be taken into account during medical treatment of opiate addicts and in the use of morphine to decrease pain in various clinical situations.
 ...
PMID:Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice. 1265 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>