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

The authors examine the pharmacological characteristics, distribution and clinical effects of natural (somatostatin) and synthetic (octreotide) growth hormone release inhibitors (GHRIH). They mainly discuss the analgesic effect of these substances using intraspinal, epidural and subarachnoid administration. The intraspinal use of somatostatin and its synthetic analog, octreotide, are not without risks: among these, it is worth recalling the neurotoxic and vasomotor effects. Further studies may more clearly define these and other secondary effects and also the real indications for these drugs in the context of analgesics for intraspinal use. It is hypothesised that somatostatin and octreotide, owing to their analgesic capacities, may replace the intraspinal administration of opioids in a number of clearly defined clinical conditions, such as severe pain in which opioids are contraindicated.
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PMID:[Analgesic effects of natural growth hormone release inhibitors and their synthetic analogs. Intraspinal administration]. 913 30

Epidemiologic studies continue to provide evidence that fibromyalgia is part of a spectrum of chronic widespread pain. The prevalence of chronic widespread pain is several times higher than fibromyalgia as defined by the 1990 American College of Rheumatology guidelines. There is now compelling evidence of a familial clustering of fibromyalgia cases in female sufferers; whether this clustering results from nature or nature remains to be elucidated. A wide spectrum of fibromyalgia-associated symptomatology and syndromes continues to be described. During the past year the association with interstitial cystitis has been explored, and neurally mediated hypotension has been documented in both fibromyalgia and chronic fatigue syndrome. Abnormalities of the growth hormone-insulin-like growth factor-1 axis have been also documented in both fibromyalgia and chronic fatigue syndrome. The commonly reported but anecdotal association of fibromyalgia with whiplash-type neck trauma was validated in a report from Israel. However, unlike North America, 100% of Israeli patients with posttraumatic fibromyalgia returned to work. Basic research in fibromyalgia continues to pinpoint abnormal sensory processing as being integral to understanding fibromyalgia pain. Drugs such as ketamine, which block N-methyl-D-aspartate receptors (which are often upregulated in central pain states) were shown to benefit fibromyalgia pain in an experimental setting. The combination of fluoxetine and amitriptyline was reported to be more beneficial than either drug alone in patients with fibromyalgia. A high prevalence of autoantibodies to cytoskeletal and nuclear envelope proteins was found in chronic fatigue syndrome, and an increased prevalence of antipolymer antibodies was found in symptomatic silicone breast implant recipients who often have fibromyalgia.
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PMID:Fibromyalgia, chronic fatigue syndrome, and myofascial pain. 956 2

Microencapsulated genetically engineered cells have the potential to treat a wide range of diseases. For example, in experimental animals, implanted microencapsulated cells have been used to secrete growth hormone to treat dwarfism, neurotrophic factors for amyotrophic lateral sclerosis, beta-endorphin to decrease pain, factor XI for hemophilia B, and nerve growth factors to protect axotomized neurons. For some applications, microencapsulated cells can even be given orally. They can be engineered to remove unwanted molecules from the body as they travel through the intestine, and are finally excreted in the stool without being retained in the body. This application has enormous potential for the removal of urea in kidney failure, ammonia in liver failure and amino acids such as phenylalanine in phenylketonuria and other inborn errors of metabolism.
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PMID:Therapeutic uses of microencapsulated genetically engineered cells. 961 2

The symptomatology characterizing fibromyalgia (FM) comprises three systems: the musculoskeletal system with widespread muscular pain, neuroendocrine disorders, and psychological distress including depression. Though the most prominent symptom of FM is pain in defined points of the musculoskeletal system, the numerous other somatoform and psychological disorders suppose a common primary disturbance which we consider to originate within higher levels of the central nervous system. Recent studies of the entire endocrine profile of FM patients following a simultaneous challenge of the hypophysis with corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone, growth hormone-releasing hormone, and luteinizing hormone-releasing hormone support the hypothesis that an elevated activity of CRH neurons determines not only many symptoms of FM but may also cause the deviations observed in the other hormonal axes. Hypothalamic CRH neurons thus may play a key role not only in "resetting" the various endocrine loops but possibly also nociceptive and psychological mechanisms as well.
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PMID:Hormonal pertubations in fibromyalgia syndrome. 1041 28

There is an abundance of cannabinoid (CB) receptors for derivatives of cannabis plants in the brain and throughout the body, and several naturally occurring arachidonic acid derivatives can activate these receptors. The specific objective of this study was to activate these CB receptors in castrated male calves through administration of several CB agonists and to measure immediate changes in concentrations of several serum hormones, respiration rate, and sensitivity to pain. The rationale for the study was that exogenous activation of CB receptors might reveal whether the endogenous CB system (consisting of receptors and endogenous ligands) plays a role in the stress response of animals and specifically whether the activated CB system might be part of a coping mechanism to combat stress. Intravenous administration of three CB agonists (anandamide, methanandamide and WIN 55212-2) to nine castrated male calves under non-stress conditions provoked immediate increases of serum cortisol and respiration rate as well as rapidly caused hypoalgesia to cutaneous pain and thermal stimuli. Although anandamide and methanandamide did not affect serum prolactin, administration of another CB agonist (WIN 55212-2) did increase serum prolactin abruptly. None of the CB agonists affected serum growth hormone. In summary, many of the changes following administration of CB agonists were similar to a stress response in this species, but there were some agonist-specific differences, notably regarding prolactin secretion, as well as differences between calves and observations made in other species. Although CB receptors in calves may be activated by endogenous ligands during exposure to some stressors, the present results are also consistent with this CB system being part of a coping mechanism that helps animals deal with imposed stressors.
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PMID:Endocrine and other responses to acute administration of cannabinoid compounds to non-stressed male calves. 1041 18

Thymic peptides, a heterogenous family of polypeptidic hormones synthesized within the thymus, not only exert important regulatory effects within both the immune and neuroendocrine systems but are also themselves subject to control by hormones derived from the hypothalamic-pituitary-adrenal axis (HPA) and other endocrine glands. Regarding thymic hormonal function, thymulin production is up-regulated by several hormones, including prolactin, growth hormone and thyroid hormones. Other aspects of the physiology of thymic epithelial cells can also be modulated by hormones and neuropeptides, particularly cytokeratin expression, cell growth and production of extracellular matrix proteins, thus characterizing the pleiotrophic action of these molecules on the thymic epithelium. Conversely, thymic-derived peptides also regulate hormone release from the HPA axis and may act directly on target endocrine glands of this axis, modulating gonadal tissues. In addition, it has recently been shown that thymulin can modulate some peripheral nervous sensory functions, including those related to sensitivity to pain. According to the dose given, thymulin induces or reduces hyperalgesia related to both mechanical and thermal nociceptors and thus represents an important interface between the immune, endocrine and nervous systems.
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PMID:Role of thymic peptides as transmitters between the neuroendocrine and immune systems. 1057 53

Patient compliance is of vital importance for the outcome of any medical therapy. Compliance is especially a problem in long-term treatment of non-life threatening diseases, such as growth retardation in children. Until recently, all human growth hormone (hGH) products required a reconstitution process. Norditropin((R)) SimpleXx(TM) is a liquid formulation of the biosynthetic hGH product Norditropin((R)), and, together with an improved NovoPen((R)) 1.5, NordiPen(TM), and an auto-insertion device, PenMate(TM)/NordiPenMate(TM), it has been developed in order to ease the injection process for patients. A randomized, open, multicentre, crossover trial compared Norditropin((R)) SimpleXx(TM)/improved NovoPen((R)) 1.5 with freeze-dried Norditropin((R)) PenSet((R))/Nordiject((R)). A total of 67 children with GH deficiency, aged 5-18 years, were treated with either Norditropin((R)) SimpleXx(TM) for 6 weeks followed by Norditropin((R)) for 6 weeks or the opposite (sequences I and II, respectively). Acceptability/convenience and pain perception were evaluated by questionnaire after each period. The function and handling of the PenMate(TM) were evaluated in a Dutch trial by 27 GH-treated children with intrauterine growth retardation, aged 4-16 years, and their parents. All children were accustomed to using the Nordiject((R)) pen. The evaluation of the PenMate(TM) was based on a questionnaire. A similar trial was conducted in England, in which the NordiPen(TM) and the NordiPenMate(TM) were evaluated by 25 GH-treated children and their parents. Norditropin((R)) SimpleXx(TM) was found to be easier to inject by 64% of the children, and 98% of the children found the system easier to use overall. There was no difference in pain perception between the two administration systems, as judged by questionnaires and visual analogue scale score. Three out of four patients preferred to continue treatment with Norditropin((R)) SimpleXx(TM). The safety profiles of the two systems were similar. In the Dutch trial, the PenMate(TM) was found to be easy and safe to handle, even for very young children (aged 4-5 years). Of patients who took a long time to get used to the injections, 73% found that the new pen would help. A total of 88% of the children would prefer to use the PenMate(TM) in the future. Positive results of the handling tests were also reported in the British trial. The use of Norditropin((R)) SimpleXx(TM) and the auto-insertion device may improve patient compliance.
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PMID:Norditropin SimpleXx: a liquid human growth hormone formulation, a pen system and an auto-insertion device. 1059 53

The symptomatology of the fibromyalgia syndrome (FMS) often resembles an alteration in central nervous set points at least in three systems. The patients suffer under chronic pain in the region of the locomotor system, presumably reflecting a disturbed central processing of pain. Anxiety and depression often characterizes the clinical picture. Almost all of the hormonal feedback mechanisms controlled by the hypothalamus are altered. Characteristic for FMS patients are the elevated basal values of ACTH, follicle-stimulating hormone (FSH), and cortisol as well as lowered basal values of insulin-like growth factor 1 (IGF-1, somatomedin C), free triiodothyronine (FT3), and oestrogen. In FMS patients, the systemic administration of the relevant releasing hormones of corticotropin-releasing hormone (CRH), growth hormone-releasing hormone (GHRH), thyreotropin-releasing hormone (TRH), and luteinizing hormone-releasing hormone (LHRH) leads to increased secretion of ACTH and prolactin, whereas the degree to which TSH can be stimulated is reduced. The stimulation of the hypophysis with LHRH in female FMS patients during their follicular phase results in a significantly reduced LH response. All in all, the typical alterations in set points of hormonal regulation that are typical for FMS patients can be explained as a primary stress activation of hypothalamic CRH neurons caused by the chronic pain. In addition to the stimulation of pituitary ACTH secretion, CRH activates somatostatin on the hypothalamic level, which in turn inhibits the release of GH and TSH on the hypophyseal level. The lowered oestrogen levels could be accounted for both via an inhibitory effect of the CRH on the hypothalamic release of LHRH or via a direct CRH-mediated inhibition of the FSH-stimulated oestrogen production in the ovary. Serotonin (5HT), precursors like tryptophan (5HTP), drugs which release 5HT or act directly on 5HT receptors stimulate HPA axis, indicating a stimulatory serotonergic influence on HPA axis function. Therefore activation of the HPA axis may reflect an elevated serotonergic tonus in the central nervous system of FMS patients.
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PMID:Neuroendocrine and hormonal perturbations and relations to the serotonergic system in fibromyalgia patients. 1102 24

Fibromyalgia is an extremely common chronic condition that can be challenging to manage. Although the etiology remains unclear, characteristic alterations in the pattern of sleep and changes in neuroendocrine transmitters such as serotonin, substance P, growth hormone and cortisol suggest that dysregulation of the autonomic and neuroendocrine system appears to be the basis of the syndrome. The diagnosis is clinical and is characterized by widespread pain, tender points and, commonly, comorbid conditions such as chronic fatigue, insomnia and depression. Treatment is largely empiric, although experience and small clinical studies have proved the efficacy of low-dose antidepressant therapy and exercise. Other less well-studied measures, such as acupuncture, also appear to be helpful. Management relies heavily on the physician's supportive counseling skills and willingness to try novel strategies in refractory cases.
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PMID:Treating fibromyalgia. 1185 21

Osteogenesis imperfecta (OI), an inherited connective tissue disorder of remarkable clinical variability, is caused by a quantitative or qualitative defect in collagen synthesis and is characterised by bone fragility. The number of fractures and deformities, and the age at which they begin greatly influence the prognosis and the achievement of walking and autonomy. A multidisciplinary team approach is essential for diagnosis, for communication with patient and parents, and to tailor treatment needs to the severity of the disease and the age of the patient. Three types of treatment are available: nonsurgical management (physical therapy, rehabilitation, bracing and splinting), surgery (intramedullary rod positioning, spinal and basilar impression surgery), and drugs to increase the strength of bone and decrease the number of fractures. An aggressive rehabilitative approach is indicated to optimise functional ability and walking capacity; appropriately timed surgery to insert intramedullary rods provides improved function of extremities. Despite a high rate of complications, intramedullary telescopic roding has proven to be the most successful method for preventing and correcting fractures and deformities of long bones, improving walking capability and leading to successful rehabilitation of even severely affected patients. Surgery may be required in patients with progressive spinal deformity and in those with symptomatic basilar impression. Hearing function, dentinogenesis imperfecta, cardiac and respiratory function, and neurological changes must be monitored. The causal defect of the disease cannot be corrected with medical treatment and, currently, only symptomatic therapy is available. In recent years growth hormone (GH) and bisphosphonate agents have been used in OI therapy. GH is beneficial in patients with moderate forms of OI, showing a positive effect on bone turnover, bone mineral density and height velocity rate. Bisphosphonates have proved beneficial in children with severe OI, increasing bone mineral density and reducing the fracture rate and pain with no adverse effects reported. These data require confirmation in double-blind controlled studies; however, bisphosphonates have markedly improved morbidity in patients with OI. Future developments in genetic therapy may be directed towards either replacing cells carrying the mutant gene with normal cells or silencing the mutant allele using antisense suppression therapy, thus transforming a biochemically severe form of OI into a mild form.
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PMID:Osteogenesis imperfecta: practical treatment guidelines. 1112 46


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