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)

Arginine has been used by millions of athletes over the past 20 years to enhance production of human growth hormone. The effects of arginine supplementation include increased fat burning and muscle building, enhanced immunity, and improvement in erectile function in men. Excessive doses of basic amino acids such as ethionine, methionine and lysine are known to damage the rat pancreas. Recent studies have demonstrated that excessive doses of arginine induce necrotizing pancreatitis in rats. In this article, we report a 16-year-old male patient hospitalized in our clinic because of severe pain in upper abdomen, nausea and vomiting who was suspected to have arginine-induced acute pancreatitis.
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PMID:Acute pancreatitis possibly due to arginine use: a case report. 1526 24

We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.
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PMID:Long-term effects of octreotide on pituitary gigantism: its analgesic action on cluster headache. 1551 76

By using in situ hybridization histochemistry the distribution of growth hormone (GH) receptor mRNA was examined in the rat brain stem and spinal cord. Dense labeling was seen in the arcuate nucleus of the hypothalamus, as reported previously, but also in several other areas, including the locus coeruleus, the area postrema, and the commissural part of the nucleus of the solitary tract. Other labeled structures included the superior lateral parabrachial nucleus, the facial, hypoglossal and trigeminal motor nuclei, the nucleus incertus, the dorsal tegmental nucleus, the dorsal raphe nucleus, the nucleus of the trapezoid body, and the superficial layers of the dorsal horn of the spinal cord. These findings provide support for a direct action of GH on brain regions involved in various aspects of homeostatic control. Thus, the distribution of GH receptor mRNA to visceral sensory and motor structures is consonant with a role of GH in the regulation of food intake and energy homeostasis. Its presence in the superficial dorsal horn of the spinal cord indicates a role for GH in the initial processing of fine afferent input, and may help explain the beneficial effects of GH replacement in certain unclear pain conditions.
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PMID:Distribution of growth hormone receptor mRNA in the brain stem and spinal cord of the rat. 1566 98

Insulin-like growth factor-1 (IGF-1) and its receptors share considerable homology with insulin and insulin receptors, and their respective signaling pathways interact at the post receptor level. While the growth hormone (GH)-IGF-1 axis principally regulates tissue growth and differentiation, insulin exerts it primary effects on fuel metabolism. However, these two endocrine systems interact at multiple levels and in diabetes mellitus the GH-IGF-1 axis is grossly disturbed, with increased secretion of GH, reduced plasma levels of IGF-1, and complex tissue-specific changes in IGF binding proteins (IGFBPs). These observations have given rise to the view that GH-IGF-1 axis dysfunction, particularly low plasma levels of circulating IGF-1, probably play a significant role in several aspects of the pathophysiology of diabetes mellitus, including insulin resistance and poor glycemic control, and may also influence the development of microvascular complications. The availability of recombinant human IGF-1 (rhIGF-1; mecasermin), used either alone or in combination with insulin, has led to experimental studies and clinical trials in humans testing these hypotheses. These studies have examined the impact of subcutaneous rhIGF-1 injections on sensitivity and metabolic parameters. In patients with type 1 and 2 diabetes mellitus, insulin sensitivity is significantly improved, insulin requirements are reduced, and glycemic control of dyslipidemia is generally improved in short-term studies. rhIGF-1 is a particularly attractive possibility in patients with type 2 diabetes mellitus, where insulin resistance is the fundamental problem. Some patients with genetic syndromes of severe insulin resistance also benefit from treatment with rhIGF-1, which can bypass blocks in the insulin signaling pathway. The common adverse effects reported for rhIGF-1 are dose-related and include edema, jaw pain, arthralgia, myalgia, hypotension, injection site pain, and less commonly, Bell's palsy and raised intracranial pressure. Although disturbance of the GH-IGF-1 axis participates in the development of diabetic complications, the functional consequences of the complex changes in IGFBP expression at the tissue level are uncertain, and it is not known whether systemic IGF-1 therapy or other manipulations of the GH-IGF-1 axis would be helpful or harmful. Experimentally, IGF-1 has a protective effect on neuropathy, and could find an application in the healing of neuropathic ulcers. The potential benefits of IGF-1 therapy in diabetes mellitus have yet to be realised.
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PMID:Therapeutic potential of insulin-like growth factor-1 in patients with diabetes mellitus. 1583 92

Growth hormone is essential for normal linear growth and the attainment of an adult mature height. It also plays an important role in cartilage growth and the attainment of normal bone mass. There is only one rheumatic disorder, namely acromegaly, in which abnormalities of growth hormone production play a major etiologic role. However, there is increasing appreciation that suboptimal growth hormone secretion, leading to a state of adult growth hormone deficiency, may occur in the setting of chronic inflammatory disease, chronic corticosteroid use, and fibromyalgia. Therefore, the evaluation and effective management of growth hormone oversecretion and undersecretion is relevant to practicing rheumatologists.
Curr Pain Headache Rep 2005 Oct
PMID:Growth hormone in musculoskeletal pain states. 1615 62

Phosphate diabetes is defined as inadequate tubular reabsorption. Hypophosphatemia is responsible for most of the clinical manifestations, which vary with the age of the patient and the severity of the phosphate wasting. Vitamin D-resistant rickets in children or osteomalacia in adults, osteoporosis, bone pain including spinal pain, and pain in the joints and periarticular areas are the main manifestations. Several factors are known to affect tubular phosphate reabsorption via the sodium/phosphate cotransporters located on the tubular cell membranes. Factors that decrease phosphate reabsorption include a high intake of dietary phosphate, acidosis, parathyroid hormone (PTH), PTH-related peptide (PTHrp), glucocorticoid therapy, calcitonin, and vitamin D. On the other hand, a low-phosphate diet, alkalosis, growth hormone, insulin, IGF-1, and thyroid hormones increase tubular phosphate reabsorption. Physiological concepts about tubular phosphate reabsorption have been radically changed by the recent identification of phosphaturic factors called phosphatonins. The most extensively studied phosphatonin to date is fibroblast growth factor 23 (FGF23), which was first identified in patients with tumor-induced osteomalacia and shown to be secreted by the neoplastic cells. The FGF23 has also been implicated in autosomal dominant hypophosphatemic rickets, in which a gene mutation results in production of abnormal FGF23 that resists hydrolysis. In healthy individuals, FGF23 contributes to regulate phosphate reabsorption via Na/Pi cotransporters. Other phosphatonins may exist, such as matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein 4 (SFRP4), whose role remains to be defined. The part played by these proteins in idiopathic renal phosphate wasting in adults needs to be investigated.
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PMID:Phosphate diabetes, tubular phosphate reabsorption and phosphatonins. 1621 71

Physiotherapy, rehabilitation, and orthopedic surgery are the mainstay of treatment in moderate to severe forms of osteogenesis imperfecta (OI). Nevertheless, medical treatment with bisphosphonates can bring significant additional improvements. Benefits include decreased pain, lower fracture incidence, and better mobility. Among the various bisphosphonates, intravenous pamidronate has been studied in most detail. It is unclear whether oral bisphosphonates are as effective as intravenous pamidronate. As the effect of bisphosphonates on the skeleton is largest during growth, it appears logical to start medical therapy of OI patients as early as possible. However, the optimal treatment regimen and the long-term consequences of pamidronate treatment in children are currently unknown. Given these uncertainties, treatment with bisphosphonates during growth should be reserved for patients who have significant clinical problems, such as vertebral compression fractures or long bone deformities. Medical therapies other than bisphosphonates, such as growth hormone and parathyroid hormone, play a minor role at present. Gene-based therapy currently remains in the early stages of preclinical research.
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PMID:Osteogenesis imperfecta, current and future medical treatment. 1627 81

Several hormones are administered by daily subcutaneous injections. Pain caused by subcutaneous injection is an unpleasant condition, which can limit patient compliance. The objective of the present study was to evaluate the perception of pain by subcutaneous injection of two different and commercially available solutions for dispensing recombinant human growth hormone. The solutions are characterised by pH, conservation, and buffer. Isotonic saline was used as reference solution. Fifty-four healthy volunteers (mean age (+/-S.E.M.): 35.5+/-1.1 years) were recruited to the double-blind, randomised study. All injections were performed pairwise (right and left thigh) in one day by the same experienced nurse. Perception of pain was evaluated by the volunteers immediately after injection and 2 min. after injection into the thigh of three formulations, which differed with respect to pH and buffers (histidine, citrate and saline, respectively). Significantly more participants (38/54) found than the citrate buffer caused more pain than the histidine buffer immediately after injection (P=0.002). Histidine buffer did not cause more pain than saline (P=0.996). After 2 min., there was no difference between the histidine and the citrate buffer (P=1.00), nor between the histidine buffer and saline (P=1.00). In summary, the solution-containing citrate as buffer caused more pain after subcutaneous injection than the solution with histidine as buffer. Considering patient compliance, it seems advisable to employ histidine-buffered solution rather than citrate-buffered solution for dispensing recombinant human growth hormone by daily subcutaneous injections.
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PMID:Pain perception after subcutaneous injections of media containing different buffers. 1644 98

Deorphanised G-protein-coupled receptors represent new and expanding targets for drug development. Neuropeptide B (NPB) and W (NPW) have recently been identified as the cognate endogenous ligands for the orphan receptor GPR7, now designated as NPBW(1). NPB and NPW also bound to a second related orphan receptor, GPR8, now designated as NPBW(2) that is present in humans but not rats or mice. In humans, high levels of NPW mRNA have been visualised in the substantia nigra, whereas moderate expression levels have been detected in the amygdala and hippocampus. In peripheral tissues, expression of NPW mRNA has been confirmed in the progenital system, comprising the kidney, testis, uterus, ovary and placenta, and also in stomach homogenates. Immunocytochemical, molecular biological and autoradiography techniques have revealed a discrete CNS distribution for NPBW(1) in human, mouse and rat. Highest expression of NPBW(1) mRNA and protein was identified in the amygdala and hypothalamic nuclei known to regulate feeding behaviour. [(125)I]-NPW bound with a single high affinity to rat amygdala, K(D)=0.44 nM and 150 fmol mg(-1) protein. Physiological studies demonstrate that intracerebroventricular infusion of NPBW(1) ligands modulates feeding behaviour, regulates the release of corticosterone, prolactin and growth hormone while also manipulating pain pathway. Mouse knockout models of the gene encoding either NPB or NPBW(1) have a gender-specific phenotype, with moderate obesity evident in males but not females. Further investigation is required to elucidate the precise physiological role of NPB and NPW as neurotransmitters.
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PMID:Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system. 1684 39

Relief of symptoms can be achieved following surgery for growth hormone (GH)-secreting adenomas, as well as after pharmacological therapy with somatostatin analogs. Recently, long-acting somatostatin analog depot formulations, octreotide LAR and lanreotide SR have become available. Somatostatin analogs control GH/insulin-like growth factor (IGF)-1 excess, induce tumor shrinkage in a high proportion of patients, improve symptoms of acromegaly with relatively limited side effects and are successfully administered in patients not suitable for surgery. Furthermore, preoperative somatostatin analogs have been suggested to improve outcome for tumors with limited invasiveness, while surgical tumor debulking in cases that are, at least partially, somatostatin resistant, increases the achievement of normal IGF-1 levels by postoperative somatostatin analog treatment. Effective control of hypertension, as well as diabetes, is mandatory in order to reduce the increased vascular morbidity/mortality. Control of GH/IGF-1 excess generally improves glucose metabolism. Somatostatin analogs improve insulin sensitivity, exerting, however, a concomitant direct inhibitory effect on insulin secretion, with a net balance leaning towards a deterioration in glucose homeostasis. As a result, oral insulin secretagogues (and/or insulin) should probably be preferred to insulin sensitizers in acromegalic patients developing diabetes while on somatostatin analogs. Nevertheless, glucose tolerance remains normal in most of the nondiabetic acromegalic patients, while diabetic acromegalic patients on insulin are at risk for hypoglycemia during initiation of somatostatin analog therapy. Although successful management of acromegaly has been associated with improvement in morphological and functional parameters of cardiomyopathy, limited and conflicting information is available regarding the effect on blood pressure control. Contradictory results have also been reported regarding sleep hypopnea or apnea in treated acromegalic patients. As acromegalic skeletal abnormalities are rather irreversible, apneic episodes may persist after normalization of hormonal levels. Aggressive therapy, including surgery, pharmacological treatment and, in some cases, pituitary irradiation, aiming at normalization of IGF-1 levels, is required for arthropathy management. Some improvement in pain, crepitus and range of motion has been observed after treatment with somatostatin analogs. Information on the impact of disease control, either by surgery or somatostatin analog treatment, on gonadal function is limited. Finally, the link between the hormonal/biochemical and the psychiatric/psychological features of acromegaly, as well as a potential basis for positive effects of somatostatin analog therapy remain unclear.
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PMID:Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs. 1704 90


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