Medications which bind to opioid receptors are increasingly being prescribed for the treatment of multiple and diverse chronic painful conditions. Their use for acute pain or terminal pain is well accepted. Their role in the long-term treatment of chronic noncancer pain is, however, controversial for many reasons. One of the primary reasons is the well-known phenomenon of psychological addiction that can occur with the use of these medications. Abuse and diversion of these medications is a growing problem as the availability of these medications increases and this public health issue confounds their clinical utility. Also, the extent of their efficacy in the treatment of pain when utilized on a chronic basis has not been definitively proven. Lastly, the role of opioids in the treatment of chronic pain is also influenced by the fact that these potent analgesics are associated with a significant number of side effects and complications. It is these phenomena that are the focus of this review. Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and in turn inadequate pain management. Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. The most common side effects of opioid usage are constipation (which has a very high incidence) and nausea. These 2 side effects can be difficult to manage and frequently tolerance to them does not develop; this is especially true for constipation. They may be severe enough to require opioid discontinuation, and contribute to under-dosing and inadequate analgesia. Several clinical trials are underway to identify adjunct therapies that may mitigate these side effects. Switching opioids and/or routes of administration may also provide benefits for patients. Proper patient screening, education, and preemptive treatment of potential side effects may aid in maximizing effectiveness while reducing the severity of side effects and adverse events. Opioids can be considered broad spectrum analgesic agents, affecting a wide number of organ systems and influencing a large number of body functions.

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Opioid complications and side effects.

Conditioned place preference (CPP) continues to be one of the most popular models to study the motivational effects of drugs and non-drug treatments in experimental animals. This is obvious from a steady year-to-year increase in the number of publications reporting the use this model. Since the compilation of the preceding review in 1998, more than 1000 new studies using place conditioning have been published, and the aim of the present review is to provide an overview of these recent publications. There are a number of trends and developments that are obvious in the literature of the last decade. First, as more and more knockout and transgenic animals become available, place conditioning is increasingly used to assess the motivational effects of drugs or non-drug rewards in genetically modified animals. Second, there is a still small but growing literature on the use of place conditioning to study the motivational aspects of pain, a field of pre-clinical research that has so far received little attention, because of the lack of appropriate animal models. Third, place conditioning continues to be widely used to study tolerance and sensitization to the rewarding effects of drugs induced by pre-treatment regimens. Fourth, extinction/reinstatement procedures in place conditioning are becoming increasingly popular. This interesting approach is thought to model certain aspects of relapse to addictive behavior and has previously almost exclusively been studied in drug self-administration paradigms. It has now also become established in the place conditioning literature and provides an additional and technically easy approach to this important phenomenon. The enormous number of studies to be covered in this review prevented in-depth discussion of many methodological, pharmacological or neurobiological aspects; to a large extent, the presentation of data had to be limited to a short and condensed summary of the most relevant findings.

Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade.

State-Trait Anxiety Inventoryによるペインクリニック外来患者の不安の評価

Fundamental statistics in psychology and education.

Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.

Opioids in chronic non-cancer pain: systematic review of efficacy and safety

Intrathecal administration of opioids is a very efficient tool in the long-term control of intractable nonmalignant pain However, despite the well known role of opioids in endocrine regulation, few data are available about possible effects on hypothalamic-pituitary function during this treatment Seventy-three patients (29 men and 44 women; mean age, 492 ± 117 yr) receiving opioids intrathecally for nonmalignant pain were enrolled for extensive endocrine investigation At the time of hormonal determination, the mean duration of opioid treatment was 266 ± 163 months; the mean daily dose of morphine was 48 ± 32 mg The control group consisted of 20 patients (11 men and 9 women; mean age, 542 ± 140 yr) with a comparable pain syndrome but not treated with opioids Decreased libido or impotency was present in 23 of 24 men receiving opioids The serum testosterone level was below 9 nmol/L in 25 of 29 men and was significantly lower than that in the control group (P < 0001) The free androgen index was

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Endocrine consequences of long-term intrathecal administration of opioids.

In a double-blind, placebo controlled crossover study, the effect of morphine on the affective and sensory pain ratings in different forms of chronic pain was investigated. Six patients suffering from central neurogenic pain, 8 from peripheral neurogenic pain and 6 from idiopathic pain participated in the study. Morphine (0.3 mg/kg bodyweight) and placebo (saline) were administered intravenously. Both the affective and sensory dimensions of pain sensation were assessed by means of the 101-point rating scale. From our results it appeared that morphine reduced the affective but not the sensory dimension of pain sensation in both groups of neurogenic pain patients. In the idiopathic pain group, neither the affective nor the sensory dimension of pain sensation were affected. The observed differences in opioid responsiveness were neither the result of differences in opioid consumption nor of differences in baseline pain levels.

Morphine differentially affects the sensory and affective pain ratings in neurogenic and idiopathic forms of pain.

The Dutch version of the McGill Pain Questionnaire was composed mainly by following R. Melzack's methodological design. The recommendations of the Finnish research team were considered and integrated. In the first phase as wide an inventory of pain descriptions as possible was drawn up. In the second phase, these pain descriptions were categorized by pain experts and students according to quality aspects. In the third phase the pain descriptions were judged according to intensity aspect as well by pain experts, by students and by pain patients. Finally a fourth phase was set up to obtain insight into the reliability and validity of the McGill Pain Questionnaire - Dutch Version (MPQ-DV).

The McGill Pain Questionnaire constructed for the Dutch language (MPQ-DV). Preliminary data concerning reliability and validity

The still ever increasing demand for sedation and/or analgesia for diagnostic and therapeutic procedures puts high pressure on anaesthesia care providers all over Europe. Since the capacity to provide that service by anaesthetists is limited in most European countries, guidelines for non-anaesthetist doctors who want to sedate patients on a high-quality level and especially in a safe way are mandatory. This paper, produced by a working party of the European Board of Anaesthesiology of the European Union of Medical Specialists (EUMS/UEMS), gives direction to those practitioners who feel responsibilities in this area of medicine. Close cooperation with anaesthesiologists seems mandatory to achieve and sustain a high-quality standard for our patients undergoing medical or surgical procedures under sedation.

Guidelines for sedation and/or analgesia by non-anaesthesiology doctors

Noxious stimulation of the rat's face evokes intense face grooming with face wash strokes almost exclusively directed to the stimulated area (e.g. Clavelou et al., Neurosci. Lett., 14 (1989) 3263-3270). Similar asymmetric face grooming behavior has been observed after transection (Berridge and Fentress, J. Neurosci., 6 (1986) 325-330) and chronic constriction of the infraorbital nerve (Vos et al., J. Neurosci., 14 (1994) 2708-2723). In the present study, the relation between unilateral facial pain and asymmetric face grooming was experimentally studied in normal, intact rats: face grooming patterns evoked by non-painful sensory disturbances in the territory of the infraorbital nerve (i.c. unilateral vibrissae clipping, anesthetic infraorbital nerve blockade, application of mineral oil on vibrissae) were compared to those evoked by noxious facial stimulation (s.c. formalin injection in mystacial pad) and those observed in unstimulated control rats, using video-analysis. Only formalin-injected rats displayed significantly more face grooming activity directed to the affected infraorbital nerve territory than unstimulated control rats. Non-painful sensory disturbances (especially mineral oil application) induced an initial bout of directed face grooming; this response was transient and short-lasting. These observations suggest that directed face grooming can be used as a sign of unilateral facial pain in freely moving rodents; unilateral non-painful facial sensory disturbances do not lead to intense and persistent directed face grooming.

Behavioral assessment of facial pain in rats: face grooming patterns after painful and non-painful sensory disturbances in the territory of the rat's infraorbital nerve

Hugo Adriaensen

Papers

Endocrine consequences of long-term intrathecal administration of opioids.

Morphine differentially affects the sensory and affective pain ratings in neurogenic and idiopathic forms of pain.

The McGill Pain Questionnaire constructed for the Dutch language (MPQ-DV). Preliminary data concerning reliability and validity

Guidelines for sedation and/or analgesia by non-anaesthesiology doctors

Behavioral assessment of facial pain in rats: face grooming patterns after painful and non-painful sensory disturbances in the territory of the rat's infraorbital nerve