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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of chronic treatment with CI988, a recently developed selective antagonist of cholecystokinin type-B receptors (CCKB receptors) on the tolerance to morphine analgesia was studied in rats with the hot plate test. 2. Morphine tolerance was induced with the use of two paradigms. Morphine was injected i.p. either in a schedule of increasing doses (1-32 mg kg-1) twice daily for 6 days or at a fixed dose (3 mg kg-1) daily for 29 days. 3. In both series of experiments, tolerance to the analgesic effect of morphine was prevented by simultaneous treatment with i.p. CI988. Chronic treatment with only CI988 daily for up to 29 days did not reduce the analgesic effect of a weekly injection of morphine. 4. CI988 did not diminish the physical dependence to morphine, as examined with naloxone precipitated withdrawal. 5. The present results provide evidence that chronic treatment with a selective CCKB receptor antagonist could prevent tolerance to the analgesic effect of morphine without affecting morphine-induced physical dependence. Application of CCK antagonists may be clinically important in treating chronic pain patients by preventing morphine tolerance and by eliminating the need to increase morphine doses to unacceptable levels.
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PMID:CI988, a selective antagonist of cholecystokininB receptors, prevents morphine tolerance in the rat. 162 46

Spinal cord injury (SCI) can cause paralysis; sensory impairment; autonomic nervous system dysfunction; and bowel, bladder, and sexual dysfunction. These impairments may lead to immobility, physical dependence, and alterations in lifestyle and self-esteem. The addition of chronic, intractable pain to these impairments can be truly devastating. Chronic pain superimposed on spinal cord injury can virtually drain the individual of strength, motivation, and will. For the spinal cord injury survivor who already faces functional loss, severe pain can further restrict even the diversional activities that are available. Thus, it may become impossible for the individual to escape his or her pain even temporarily. The various medical, physical, and surgical treatments considered to be efficacious in treating this pain are reviewed. However, although chronic pain in SCI may be managed by these therapies, a permanent cure may not result.
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PMID:Clinical management of chronic pain in spinal cord injury. 163 73

Inadequately treated acute and chronic pain remains a major cause of suffering, in spite of enormous advances in pharmacology and technology. Opioids provide a powerful, versatile, widely available means of managing this pain, but their use is too often restrained by ignorance and mistaken fears of addiction. The management of postoperative pain (perhaps the most common form of acute pain) is traditionally attempted with fixed dosages of analgesics by relatively unpredictable routes (e.g. oral, rectal and intramuscular). Intravenous opioid infusions (an improvement) risk respiratory depression and require close monitoring and titration. Patient-controlled analgesia (PCA), by contrast, permits the most efficacious medication (pure opioid agonist) by the optimal route (intravenous) under direct control of the patient, and provides high levels of satisfaction and safety. Ideally, any opioid use should be integrated with a wide spectrum of other analgesic modalities in an anaesthesiology-based 'acute pain service'. The use of opioids for chronic pain of nonmalignant origin remains controversial. There is a perceived conflict between patients' interests and those of society. However, problems (such as tolerance, physical dependence, addiction and chronic toxicity), anticipated from experience with animal experiments and pain-free abusers, seldom cause difficulties when opioids are used appropriately to treat pain (so-called 'dual pharmacology'). With sensible guidelines, and in the context of a multidisciplinary pain clinic, opioids may provide the only hope of relief to many sufferers of chronic pain.
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PMID:Treatment principles for the use of opioids in pain of nonmalignant origin. 171 22

Nalbuphine is a potent analgesic with a low side effect and dependence profile in animals and man. Nalbuphine is distinguished from other agonist/antagonist analgesics in having greater antagonist activity and fewer behavioral effects at analgesic doses than pentazocine, butorphanol or buprenorphine. At equi-analgesic doses, nalbuphine is quantitatively similar to nalorphine in regard to its large ratio of antagonist to analgetic activity. Clinical studies have confirmed this balance of strong antagonist to analgesic activity. Nalbuphine has been shown to effectively antagonize the respiratory depressant activity of narcotic analgesics while concomitantly adding to their analgetic responses. Unlike nalorphine or pentazocine, nalbuphine produces few overt behavioral or autonomic effects in animals at doses over 300 times its analgesic range. These findings are confirmed by clinical results which show that nalbuphine produces few psychotomimetic effects, even at elevated dose levels, in contrast to nalorphine or pentazocine. Nalbuphine produces limited respiratory depression in animals and in man. Significant cardiovascular effects have not been found. Nalbuphine was found to produce significantly less inhibition of gastrointestinal activity than any of the clinically useful narcotic or agonist/antagonist analgesics tested in animals. Nalbuphine's analgetic effects are reversed by naloxone doses similar to those which reverse nalorphine's agonist effects. Results in this and other tests suggest that nalbuphine is primarily a kappa-agonist/mu-antagonist analgesic. Unlike pentazocine or buprenorphine, nalbuphine does not suppress the narcotic abstinence syndrome in partly-withdrawn morphine-dependent animals or man. Rather, due to nalbuphine's strong antagonist activity, analgesic-range doses of nalbuphine severely exacerbate the withdrawal syndrome in partly-withdrawn mice, monkeys and humans. Nalbuphine also precipitates a strong abstinence response in non-withdrawn morphine-dependent animals and man. In post-addict humans, analgesic-range doses of nalbuphine are perceived as minimally morphine-like, but higher doses are judged to be progressively more nalorphine-like (i.e. dysphoric), which further limits nalbuphine's abuse potential in drug-seeking individuals. Primary dependence studies have demonstrated that physical dependence is possible at high dose levels that produce marked side effects. Other studies show that dependence is unlikely to be of significance within nalbuphine's usual analgesic range. Six-month studies in patients with chronic pain have confirmed that analgesic tolerance or physical dependence is uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nalbuphine. 298 29

Buprenorphine was administered as sublingual tablets to 70 patients suffering from chronic pain of malignant or non-malignant origin. Daily doses ranging from 0.4 mg to 3.2 mg were administered and good analgesia was reported by the majority of patients. The most common unwanted effects were drowsiness/sleepiness, nausea and/or vomiting and sweating which appeared to be dose related but the incidence of dizziness was not related to daily dose. The incidence of all these unwanted effects except drowsiness/sleepiness decreased after the first week's treatment. No buprenorphine related changes in vital signs or laboratory values were observed and no signs of tolerance or physical dependence were seen in the short term period after discontinuation of treatment. A significant positive correlation between buprenorphine plasma concentration and daily dose was observed but there was no correlation between plasma levels and pain relief.
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PMID:A long-term open, clinical and pharmacokinetic assessment of sublingual buprenorphine in patients suffering from chronic pain. 401 31

Ninety-eight patients completed a double-blind, multidose, randomized parallel study in which buprenorphine (Temgesic) was compared to morphine. Drugs were administered at approximately equipotent intramuscular doses for a maximum of three days for the relief of moderate to severe postoperative pain. The two drugs exhibited similar profiles with pain relief evident at 1/2 hour, peaking at 1 hour, and decreasing to slight relief at 4-5 hours, with no significant differences for time to remedication. The most frequent side effect was somnolence. One patient suffered sudden chest pain shortly after an injection of morphine, and one patient had moderate hypoventilation after buprenorphine; both patients recovered uneventfully. Overall, both drugs provided good or excellent analgesia in 80 per cent of the patients in this unique multidose/observational study. Thus, these data and the reported lack of withdrawal symptoms and the absence of physical dependence liability suggest that buprenorphine may have a role in the management of chronic pain.
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PMID:Multidose/observational, comparative clinical analgetic evaluation of buprenorphine. 726 31

Flupirtine is a novel non-opiate centrally acting analgesic agent with muscle relaxant properties, advocated for use in a number of pain states. Preliminary evidence suggests that flupirtine 100 to 200mg orally or 150mg rectally 3 to 4 times daily (maximum daily dose 600mg) is more effective than placebo in relieving moderate acute pain of various types. For the relief of pain due to surgery, traumatic injury, dental procedures, headache/migraine and abdominal spasms, flupirtine has proved at least as effective as the opiate analgesics codeine, dihydrocodeine and pentazocine, the nonsteroidal anti-inflammatory agents suprofen, diclofenac and ketoprofen, as well as dipyrone and paracetamol (acetaminophen). Although evidence to support a role in the treatment of chronic pain is limited, flupirtine has been found as effective as pentazocine in short term trials of patients with muscular or neuralgiform pain, dysmenorrhoea, soft tissue rheumatism or cancer pain. The safety profile of flupirtine has not yet been fully established, although initial evidence suggests that adverse reactions, while frequent, are usually minor in nature. The most common reactions are drowsiness, dizziness, dry mouth and various gastrointestinal complaints. In comparison with opiate drugs, flupirtine appears to produce fewer central nervous system effects, no respiratory or cardiovascular depression, and no overt tolerance or physical dependence on prolonged administration. If these initially favourable results are confirmed in larger long term trials, then flupirtine would appear to represent an effective analgesic for the relief of moderate pain, particularly that of musculoskeletal origin.
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PMID:Flupirtine. A review of its pharmacological properties, and therapeutic efficacy in pain states. 768 75

Addiction medicine specialists, besieged with the adverse consequences of opioids, not unreasonably develop reservations about their use. Opioid prohibition may be appropriate when working with addicts, but drug abstinence is not always the most appropriate nor optimal treatment of pain patients. Consultation concerning the management of chronic pain patients may require an attitude adjustment of challenging proportions for the addiction medicine specialist; it is a role substantially different from that usually assumed in treating alcohol- and drug-dependent patients. Rather than relentlessly pursuing psychotropic drug abstinence as the treatment goal, restoration of function should be the primary treatment goal for the chronic pain patient. Unlike the chemically dependent patient whose level of function is impaired by substance use, the chronic pain patient's level of function may improve with adequate, judicious use of medications, which may include opioids. Evaluating for addiction in a patient who is prescribed long-term opioids for pain control is often problematic. While the concept of addiction may include the symptoms of physical dependence and tolerance, physical dependence and/or tolerance alone does not equate with addiction. In the chronic pain patient taking long-term opioids, physical dependence and tolerance should be expected, but the maladaptive behavior changes associated with addiction are not expected. Thus, it is the presence of these behaviors in the chronic pain patient that is far more important in diagnosing addiction.
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PMID:Opioid use in the treatment of chronic pain: assessment of addiction. 802 37

Presents a clinician's viewpoint on the tolerance of and dependence on opiates and opioids in total anesthesia and management of acute (postoperative) and chronic (cancer) pain. Clinical observations are assessed with due consideration for the theoretical (pharmacological) studies. The author analyzes prolonged therapy with different opiates and opioids and the short-term use in massive doses at different stages of surgery. Tolerance to morphine rapidly forms during therapy of chronic pain, and the narcotic doses have to be progressively increased. Tolerance to opioids, such as tramal and buprenorphine, is less expressed. These agents are less hazardous as regards drug dependence, which was proven for tramal by the naloxone test. Clinical manifestations of physical dependence on opiates at different stages of surgical treatment are discussed for the first time. The main last-generation opiates are characterized (tramal, buprenorphine, nalbufin, butorphanol, prosidol) by their capacity to cause physical and mental dependence. The author emphasizes the importance of a proper selection of opiates, opioids, and combinations thereof with the optimal nonopiate components in general anesthesia, postoperative analgesia, and treatment of chronic pain in order to improve the efficacy and narcological safety of analgesia.
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PMID:[The problem of opioid tolerance and dependence during clinical use thereof]. 897 62

Chronic pain represents a challenge to patients, families, employers, and the physicians who care for these individuals. Opioids remain the mainstay of the analgesic medications for the treatment of both acute and chronic pain. Controlled release preparations of morphine, oxycodone, fentanyl and long acting opioid agents such as methadone and levorphanol have been medically and ethically accepted in managing chronic cancer pain. However, the continued use of these medications for patients with chronic noncancer pain has been fiercely debated. This article attempts to reconcile the medical and ethical dilemma of using opioid medications for chronic noncancer pain. Growing clinical experience in the field of pain medicine has helped to clarify: (1) the misunderstanding of addiction, physical dependence and analgesic tolerance, (2) the misconception that chronic opioid therapy inevitably causes personality changes, depression, and impairment of cognitive and physical function, (3) the lack of information on the correct use of opioid analgesics with regard to titration and management of related side effects. The behavioral management of pain patients undergoing chronic opioid therapy is also discussed. A protocol for optimal patient management is proposed. Particular emphasis is given to the consent form, behavioral contracting, and the consequences of noncompliance. The importance of psychologic evaluation before a long-term opioid trial, to minimize future complications, is stressed. Although most patients on the opioid regimen do well, special attention must be given to patients with current addiction, a past history of addiction, or current misuse of opioid medications. Pharmacologic and conservative interventions are often warranted in those patients with significant behavioral problems. If such strategies fail, and chronic opioid therapy is deemed necessary, some treatment guidelines are offered.
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PMID:Ethical issues in the management of chronic nonmalignant pain. 931 Oct 61


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