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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For years enhancement of a patient's level of physical fitness has been an important goal in rehabilitation treatment in chronic low back pain (CLBP), based on the hypothesis that physical deconditioning contributes to the chronicity of low back pain. However, whether this hypothesis in CLBP holds is not clear. In this paper, possible mechanisms that contribute to the development of physical deconditioning in CLBP, such as avoidance behaviour and suppressive behaviour, are discussed. The presence of both deconditioning-related physiological changes, such as muscle atrophy, changes in metabolism, osteoporosis and obesity as well as deconditioning related functional changes, such as a decrease in cardiovascular capacity, a decrease in muscle strength and impaired motor control in patients with CLBP are discussed. Results of studies on the level of physical activities in daily life (PAL) and the level of physical fitness in patients with CLBP compared to healthy controls were reviewed. In studies on PAL results that were either lower or comparable to healthy subjects were found. The presence of disuse (i.e., a decrease in the level of physical activities in daily life) in patients with CLBP was not confirmed. The inconclusive findings in the papers reviewed may partly be explained by different measurement methods used in research on PAL in chronic pain. The level of physical fitness of CLBP patients also appeared to be lower or comparable to the fitness level of healthy persons. A discriminating factor between fit and unfit patients with back pain may be the fact that fit persons more frequently are still employed, and as such may be involved more in physical activity. Lastly some suggestions are made for further research in the field of disuse and deconditioning in CLBP.
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PMID:Disuse and deconditioning in chronic low back pain: concepts and hypotheses on contributing mechanisms. 1252 13

5-HT(2) family serotonin receptors, principal sites of action of serotonin in the brain, represent major molecular targets for drugs used in treating a variety of diseases including schizophrenia, depression, anxiety, eating disorders, obsessive-compulsive disorder, chronic pain conditions and obesity. The 5-HT(2) family of receptors has three members: 5-HT(2A), 5-HT(2B) and 5-HT(2C). Therefore, it is likely that subtype-selective compounds will be needed to avoid serious side effects and to enhance therapeutic indices. Unfortunately, recent insights into the structure and function of 5-HT(2A) receptors have revealed that structurally-diverse agonists and antagonists have distinct modes of interacting with 5-HT(2A) receptors, complicating efforts at structure-based drug-design. These distinct binding modes would not have been predicted based on conventional structure-activity relationships or static docking models. Fortunately, these complicated binding modes can be predicted and simulated using molecular dynamics, allowing for the possibility of structure-based drug design. Thus, provided appropriately sophisticated drug design strategies are employed, it is likely that uniquely valuable medications will result which could have great potential for treating a variety of mental and physical illnesses.
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PMID:Insights into the structure and function of 5-HT(2) family serotonin receptors reveal novel strategies for therapeutic target development. 1254 Feb 78

Misuse of opioids is associated with abnormalities of pituitary function. Patients with chronic pain frequently complain of fatigue and undergo endocrine testing. To test whether oral opioid treatment causes abnormal pituitary function we prospectively assessed pituitary function in 37 patients with chronic pain who were receiving either oral opioid analgesia or non-opioid analgesia. Oral opioid treatment was not associated with abnormal pituitary function although a few patients had abnormal results mainly related to obesity. Our results suggest that patients with chronic pain who have abnormal endocrine results should have a complete assessment, since abnormal test results cannot be attributed to their analgesia.
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PMID:Patients with chronic pain and abnormal pituitary function require investigation. 1284 75

The following conclusions can be made based on review of the evidence: There is limited but positive evidence that select physical modalities are effective in managing chronic pain associated with specific conditions experienced by adults and older individuals. Overall, studies have provided the most support for the modality of therapeutic exercise. Different physical modalities have similar magnitudes of effects on chronic pain. Therefore, selection of the most appropriate physical modality may depend on the desired functional outcome for the patient, the underlying impairment, and the patient's preference or prior experience with the modality. Certain patient characteristics may decrease the effectiveness of physical modalities, as has been seen with TENS. These characteristics include depression, high trait anxiety, a powerful others locus of control, obesity, narcotic use, and neuroticism. The effect on pain by various modalities is generally strongest in the short-term period immediately after the intervention series, but effects can last as long as 1 year after treatment (e.g., with massage). Most research has tested the effect of physical modalities on chronic low back pain and knee OA. The effectiveness of physical modalities for other chronic pain conditions needs to be evaluated more completely. Older and younger adults often experience similar effects on their perception of pain from treatment with physical modalities. Therefore, use of these modalities for chronic pain in older adults is appropriate, but special precautions need to be taken. Practitioners applying physical modalities need formal training that includes the risks and precautions for these modalities. If practitioners lack formal training in the use of physical modalities, or if modality use is not within their scope of practice, it is important to consult with and refer patients to members of the team who have this specialized training. Use of a multidisciplinary approach to chronic pain management is of value for all adults and older individuals in particular [79-81]. Historically, physical therapists have been trained to evaluate and treat patients with the range of physical modalities discussed in this article. Although members of the nursing staff traditionally have used some of these modalities (e.g. some forms of heat or cold and massage), increasing numbers of nurses now are being trained to apply more specialized procedures (e.g., TENS). Healthcare professionals must be knowledgeable about the strength of evidence underlying the use of physical modalities for the management of chronic pain. Based on the limited research evidence available (especially related to assistive devices, orthotics, and thermal modalities), it often is difficult to accept or exclude select modalities as having a potential role in chronic pain management for adults and older individuals. Improved research methodologies are needed to address physical modality effectiveness better.
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PMID:Physical modalities in chronic pain management. 1456 4

Extensive research into the functions of glutamate and glutamate receptors in the central nervous system (CNS) has shown an essential role of metabotropic glutamate (mGlu) receptors in normal brain functions, but also in neurological and psychiatric disorders. The precise functions of these receptors remain undefined, and progress toward understanding their functions has been hampered by the lack of selective ligands with appropriate pharmacokinetic properties. The Group I mGlu receptor, mGlu5, is well positioned to regulate and fine-tune neuronal excitability and synaptic transmission through its modulation of various signal transduction pathways and interactions with other transmitter systems. Therefore, the mGlu5 receptor may be an important therapeutic target for the treatment of disorders of the central nervous system. The discovery of MPEP 3, a non-competitive mGlu5 receptor antagonist, provided a potent, selective, systemically active tool compound for proof of concept studies in animal models of various disease states. These studies have led to greater understanding of possible therapeutic applications of mGlu5 receptor antagonists in recent years, suggesting their use in a number of disease states, including chronic pain, various psychiatric and neurological disorders, substance abuse and withdrawal, obesity and gastroesophageal reflux disease (GERD). Together, these findings have intensified efforts to find other non-competitive mGlu5 receptor antagonists and have led to the discovery of several second-generation compounds, a few of which are in preclinical evaluations. There have been several recent reviews on mGlu receptor. This article highlights recent efforts on the design, synthesis and development of novel, non-competitive mGlu5 receptor antagonists and studies to understand their in vitro mechanisms of action and in vivo pharmacological profiles. Emphasis is also given to recent advances in the potential therapeutic applications of non-competitive mGlu5 receptor antagonists.
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PMID:Recent advances in non-competitive mGlu5 receptor antagonists and their potential therapeutic applications. 1617 34

Since the discovery of an endogenous cannabinoid system, research into the pharmacology and therapeutic potential of cannabinoids has steadily increased. Two subtypes of G-protein coupled cannabinoid receptors, CB(1) and CB(1), have been cloned and several putative endogenous ligands (endocannabinoids) have been detected during the past 15 years. The main endocannabinoids are arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG), derivatives of arachidonic acid, that are produced "on demand" by cleavage of membrane lipid precursors. Besides phytocannabinoids of the cannabis plant, modulators of the cannabinoid system comprise synthetic agonists and antagonists at the CB receptors and inhibitors of endocannabinoid degradation. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues, including immune system, reproductive and gastrointestinal tracts, sympathetic ganglia, endocrine glands, arteries, lung and heart. There is evidence for some non-receptor dependent mechanisms of cannabinoids and for endocannabinoid effects mediated by vanilloid receptors. Properties of CB receptor agonists that are of therapeutic interest include analgesia, muscle relaxation, immunosuppression, anti-inflammation, antiallergic effects, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects. The current main focus of clinical research is their efficacy in chronic pain and neurological disorders. CB receptor antagonists are under investigation for medical use in obesity and nicotine addiction. Additional potential was proposed for the treatment of alcohol and heroine dependency, schizophrenia, conditions with lowered blood pressure, Parkinson's disease and memory impairment in Alzheimer's disease.
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PMID:Cannabinoids. 1626 85

Clinical trial data are beginning to emerge with respect to the therapeutic efficacy of cannabis extracts for the treatment of chronic pain. Although there is some evidence of efficacy, a major issue concerns the narrow margin between doses producing therapeutic effects and those producing the "highs" associated with cannabis misuse. In addition, long-term use is associated with an increased risk of psychiatric illness. These negative aspects constrain the doses of cannabis extracts and psychoactive cannabinoids that can be given to patients, and raise the risk that properly conducted clinical trials with too low dosages will impact negatively on subsequent drug development in this field. However, recent research has opened up a number of avenues whereby compounds acting directly upon cannabinoid (CB) receptors may have therapeutic potential. In this review, two such areas are discussed, namely a) the possible use of peripherally acting CB agonists and CB2 receptor-selective agonists for the treatment of pain, and b) the possible utility of CB2 receptor agonists for the prevention of stress-induced exacerbations of skin disorders such as psoriasis. A second area of drug development at present is that of CB1 receptor antagonists/inverse agonists, spearheaded by rimonabant, for the treatment of obesity and as an aid for smoking cessation. An important aspect of these compounds is their efficacy and selectivity, and this is discussed in detail in the present review.
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PMID:Pharmacological properties and therapeutic possibilities for drugs acting upon endocannabinoid receptors. 1637 86

There is convincing evidence that acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting, as well as postoperative dental pain. Less convincing data support AP's efficacy for chronic pain conditions, including headache, fibromyalgia and low back pain. There is no evidence that AP is effective in treating addiction, insomnia, obesity, asthma or stroke deficits. AP seems to be efficacious for alleviating experimental pain by increasing pain thresholds in human subjects and it appears to activate analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes some time to develop and to resolve. Furthermore, repetitive use of AP analgesia can result in tolerance that demonstrates cross-tolerance with morphine. However, it appears that not all forms of AP are equally effective for providing analgesia. In particular, electro-AP seems to best deliver stimuli that activate powerful opioid and nonopioid analgesic mechanisms. Thus, future carefully controlled clinical trials using adequate electro-AP may be able to provide the necessary evidence for relevant analgesia in chronic pain conditions, such as headache, fibromyalgia, irritable bowel syndrome and low back pain.
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PMID:Mechanisms of acupuncture analgesia for clinical and experimental pain. 1673 14

Glucocorticoids contribute fundamentally to the maintenance of basal and stress-related homeostasis in all higher organisms. These hormones influence a large percentage of the expressed human genome and their effects spare almost no organs or tissues. Glucocorticoids influence many functions of the central nervous system, such as arousal, cognition, mood and sleep, the activity and direction of intermediary metabolism, the maintenance of a normal cardiovascular tone, the activity and quality of the immune and inflammatory reaction, including the manifestations of the sickness syndrome, as well as growth and reproduction. The numerous actions of glucocorticoids are mediated by a set of at least 16 glucocorticoid receptor (GR) isoforms forming homo- or hetero-dimers. The GRs consist of multifunctional domain proteins operating as ligand-dependent transcription factors that interact with many other cell signaling systems. The presence of multiple GR monomers and dimers expressed in a cell-specific fashion at different quantities with quantitatively and qualitatively different transcriptional activities suggests that the glucocorticoid signaling system is highly stochastic. Based on ample evidence, we present our conception that glucocorticoids are heavily involved in human pathophysiology and influence life expectancy. Common psychiatric and/or somatic complex disorders, such as anxiety, depression, insomnia, chronic pain and fatigue syndromes, obesity, the metabolic syndrome, essential hypertension, diabetes type 2, atherosclerosis with its cardiovascular sequelae, and osteoporosis, as well as autoimmune inflammatory and allergic disorders, all appear to have a glucocorticoid component.
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PMID:Glucocorticoid action networks and complex psychiatric and/or somatic disorders. 1751 90

The CB1 cannabinoid receptor is a G-protein coupled receptor that has important physiological roles in synaptic plasticity, analgesia, appetite, and neuroprotection. We report the discovery of two structurally related CB1 cannabinoid receptor interacting proteins (CRIP1a and CRIP1b) that bind to the distal C-terminal tail of CB1. CRIP1a and CRIP1b are generated by alternative splicing of a gene located on chromosome 2 in humans, and orthologs of CRIP1a occur throughout the vertebrates, whereas CRIP1b seems to be unique to primates. CRIP1a coimmunoprecipitates with CB1 receptors derived from rat brain homogenates, indicating that CRIP1a and CB1 interact in vivo. Furthermore, in superior cervical ganglion neurons coinjected with CB1 and CRIP1a or CRIP1b cDNA, CRIP1a, but not CRIP1b, suppresses CB1-mediated tonic inhibition of voltage-gated Ca2+ channels. Discovery of CRIP1a provides the basis for a new avenue of research on mechanisms of CB1 regulation in the nervous system and may lead to development of novel drugs to treat disorders where modulation of CB1 activity has therapeutic potential (e.g., chronic pain, obesity, and epilepsy).
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PMID:CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a. 1789 7


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