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)

Recently somatostatin (SST) intra-articular administration has been used in the treatment of some rheumatoid diseases such as rheumatoid arthritis, psoriatic arthritis and osteoarthritis with encouraging results. The aim of this study was to evaluate the efficacy and tolerability of SST intra-articularly injected, involving 20 patients with knee osteoarthritis. Treatment consisted of 4 injections, administered weekly, each of 750 mcg SST. Additionally, in six of them we evaluated the circulating levels of the insulin-like growth factor (IGF)-1 at the base-line time and then every 7 days (immediately before each dose of SST). The results revealed an improvement in pain and in joint function after intra-articular SST, confirmed by statistical analysis. The circulating levels of IGF-1 did not show significant variations following intra-articular administration of SST. The excellent tolerability and the absence of unwanted side-effects with SST allow us to foresee that intra-articular SST could be used in cases of painful knee osteoarthritis, especially in those patients in which other drugs are not appropriate. Moreover, in the absence of modifications of serum levels of IGF-1, SST could be used in athletes.
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PMID:Intra-articular injection of somatostatin in knee osteoarthritis: clinical results and IGF-1 serum levels. 783 29

Several experimental studies in the animal models and the use of calcitonin in patients with osteoarthritis, rheumatoid arthritis, and osteoporosis have shown multiple actions of this hormone, justifying its use in the wide range of osteoarthritic pathologies. We used well known animal models of tests to study chondro-tropic drugs such as: post-corticoid arthropathy, partial meniscectomy, immobilization of the lower extremity of rabbits, follow-up of the natural knee degeneration in the black mouse C57, and radiolabelled sulphates uptake by the cartilage, and have shown: (a) anticatabolic effect of salmon calcitonin as measured as GAG levels, width of articular space, and histochemical and morphologic examination of the cartilage in some model arthropathies, (b) anti-osteoporotic properties counteracting an effect of corticosteroids, (c) increased uptake of sulphates by the articular cartilage of the rat following calcitonin administration in vivo. The studies explaining mechanisms of calcitonin actions included IGF-1 assays and beta-endorphins. The former increased transiently after calcitonin administration whereas the latter increased after non-steroid anti-inflammatory agents use. Calcitonin decreased gastrin secretion with negligible effect on calcium ions and prostaglandin E2 levels in blood plasma while it potently acid secretion and increasing gastric mucus content in the stomach. The use of calcitonin in patients with arthrosis, rheumatoid arthritis, and osteoporosis with accompanying peptic and/or duodenal ulcers produced healing of peptic and/or duodenal ulcers in 75% of patients within 4 weeks with simultaneous shortening of the morning stiffness, increase in hand grip strength (in rheumatoid arthritis), and significant decrease in pain as well as an improvement in the quality of life in the majority of the treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Calcitonin in treating bone and joint lesions--clinical and experimental findings and personal experience]. 830 44

Insulin-like growth factor I (IGF-1) is trophic to sensory, motor and sympathetic neurons. Intrathecal (i.t.) administration of IGF-1 produced analgesic effects when tail flick/withdrawal latency was used as an indicator. This action was blocked by genistein (an inhibitor of tyrosine kinase) but not by atipamezol (an alpha2 adrenoreceptor antagonist), naloxone (an opioid antagonist) or glibenclamide (a blocker of ATP sensitive K+ channels). Induction of diabetes with streptozotocin (STZ, 55 mg/kg, i.v.) impaired the ability of IGF-1 to elevate nociceptive threshold. This phenomenon was not seen in normal animals rendered hyperglycemic with D-glucose (20 mmol in 2.5 ml of saline, i.p.). PCR-based assay revealed that the lumbar region of the spinal cord expresses mRNA transcripts for IGF-1 and its receptor. The rates of expression of both of these transcripts were reduced during diabetes. The above behavioral and biochemical abnormalities induced by the diabetic state were partially restored following replacement therapy with insulin. Overall, our data suggest that a receptor-linked tyrosine kinase mediates the antinociceptive effect of IGF-1. Additionally, the attenuation in the ability of IGF-1 to elevate nociceptive threshold may be a consequence of reduced gene expression of IGF-1 receptor within the spinal cord.
Pain 1998 Mar
PMID:Attenuation of IGF-1 antinociceptive action and a reduction in spinal cord gene expression of its receptor in experimental diabetes. 953 75

Fibromyalgia (FM) is a painful syndrome of nonarticular origin, characterized by fatigue and widespread musculoskeletal pain, tiredness, and sleep disturbances, without any other objective findings on examination. Interestingly, some of the clinical features of FM resemble the ones described in the adult GH-deficiency syndrome. Furthermore, insulin-like growth factor (IGF)-1 levels are frequently reduced in patients with FM. To gain further insight into the mechanisms leading to dysregulation of the GH-IGF-1 axis in these patients, we assessed 24-h spontaneous GH secretion, GH responses to GHRH, and IGF-1 and IGF binding protein (BP)-3 levels before and after 4 days treatment with human (h)GH. We found that, in comparison with controls, patients with FM exhibited a marked decrease in spontaneous GH secretion as assessed by mean GH secretion (2.5 +/- 0.4 microg/L in controls vs. 1.2 +/- 0.1 microg/L in FM, P < 0.05), pulse height (4.7 +/- 0.8 microg/L in controls vs. 2.5 +/- 0.3 microg/L in FM, P < 0.05), and pulse area (4.7 +/- 1 min/mg x L in controls vs. 2.3 +/- 0.3 min/mg x L in FM, P < 0.05). In contrast, GH responses to GHRH (100 microg, i.v.) were similar in controls (mean peak, 13.5 +/- 2.5 microg/L) and in patients with FM (12.2 +/- 3 microg/L). Finally, treatment with hGH (2 IU, s.c. daily), over 4 days, led to a clear-cut increase in plasma IGF-1 and IGFBP-3 levels in patients with FM. In conclusion, our data show that patients with FM exhibited a marked decrease in spontaneous GH secretion, but normal pituitary responsiveness to exogenously administered GHRH, thus suggesting the existence of an alteration at the hypothalamic level in the neuroendocrine control of GH in these patients. Furthermore, our finding of increased IGF-1 and IGFBP-3 levels after GH treatment, over 4 days, opens up the possibility of testing the therapeutic potential of hGH in patients with FM.
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PMID:The growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-1 axis in patients with fibromyalgia syndrome. 1048 13

Neuroendocrine deficiencies have been implicated in fibromyalgia (FM). In the present study, adrenal androgen metabolites and their relationship with health status in FM were investigated. For comparison, serum levels of other implicated neuroendocrine mediators were correlated with health status. Fifty-seven consecutive women with FM completed the Fibromyalgia Impact Questionnaire (FIQ). Fasting blood samples were taken for measurement of dehydroepiandrosterone sulphate (DHEAS), free testosterone (T), cortisol, serotonin and insulin-like growth factor-1. Normal value for DHEAS and T were obtained from 114 controls. DHEAS levels were decreased significantly in pre- and postmenopausal patients (P<0.0001 and P<0.0005, respectively). T levels were decreased significantly in premenopausal and insignificantly in postmenopausal patients (P<0.0001 and P=0.06, respectively). The following correlations between neurohormonal levels and FIQ scores were found: DHEAS (after adjustment for age) vs. pain (P<0.001) and T (after adjustment for age) versus physical functioning (P=0.002). None of the other neurohormonal levels correlated significantly with any of the FIQ scores. IGF-1 levels were lower in the obese patients as compared to those who were non-obese (P=0.03). The BMI correlated positively with pain (P<0. 001) and inversely with DHEAS levels (P=0.006). After further adjustment for BMI, the correlation between age adjusted DHEAS and pain was no longer significant. Hyposecretion of adrenal androgens was documented in FM. This was more pronounced in obese patients. Low serum androgen levels correlated with poor health status in FM. Longitudinal studies are needed to elucidate whether these are cause and/or effect relationships.
Pain 1999 Nov
PMID:Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia. 1053 4

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 a syndrome characterized by chronic musculoskeletal pain and fatigue without biological detectable disturbances. The mechanisms of this disease are unknown. It has been postulated that it can be the consequence of a chronic stress mediated mainly through the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system. These fields have been extensively studied. Results were scattered and non convincing. A reduction of growth hormone and IGF-1 levels described in a third of patients has led to a double blind random clinical trial with biogenetic growth hormone. Results were equivocal . Other hormonal systems are grossly normals and circadian rhythms are unaltered. Despite some arguments in favour of a CRH neurons hyperactivity, these results are not able to consolide a particular physiopathological mechanism and to argument for a new therapeutic approach. Many of the abnormalities may be the consequence of psychological disturbances.
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PMID:[Hormonal perturbations in fibromyalgia]. 1184 32

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

A 66-year-old man suffered from a drug-resistant, left-sided headache with autonomic signs, triggered by the supine position. The acromegalic facies initially suggested a possible increase in basal plasma levels of GH, but routine haematological controls excluded abnormal values of GH. Cerebral and facial CT scan and MRI did not detect any alterations in the nasal sinuses, except for a mucous cyst. Surgical ablation of the cyst did not alleviate the pain. Further endocrinological the pain. Further endocrinological tests demonstrated an increase of IGF-1 (somatomedin C), and another MRI scan of the sellar region confirmed the presence of a pituitary macroadenoma on the left paramedian side. After an initial improvement of the symptomatology due to trans-sphenoidal ablation of a benign GH-producing macroadenoma, the headache worsened again. Pain was well correlated with the increased plasma levels of IGF-1. The patient died suddenly for myocardial infarct.
J Headache Pain 2005 Jun
PMID:A case of a GH-producing pituitary adenoma associated with a unilateral headache with autonomic signs. 1635 97

Adult rheumatoid arthritis (RA), a systemic autoimmune disorder of unknown etiology, is characterized by dysfunctional cellular and humoral immunity, enhanced migration and attachment of peripheral macrophages and pro-inflammatory leukocytes to the synovium and articular cartilage of diarthrodial joints. The progressive destruction of cartilage and bone in RA is a result of elevated pro-inflammatory cytokine gene expression, synovial neovascularization, proteinase-mediated dissolution of articular cartilage matrix and osteoclast-mediated subchondral bone resorption. Juvenile chronic arthritis (JCA) is disease with manifestations similar to adult RA that occurs in childhood. JCA usually causes precocious joint destruction and often also presents with evidence of growth plate anomalies and reduced stature. Three proteins play an integral role in both adult RA and JCA. These are somatotropin (also called pituitary growth hormone (GH)), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). GH is responsible for regulating long bone growth and skeletal maturation through its capacity to stimulate insulin-like growth factor-I (IGF-1) synthesis by hepatocytes. Mechanisms responsible for growth plate disturbances and short stature in children with JCA include deficient GH production, GH-insensitivity resulting from defects in the GH receptor, suppressed IGF-1 synthesis or neutralization of IGF-1 action by IGF-1 binding proteins (IGFBPs). In addition, GH has also been implicated in perpetuating inflammation and pain in adult RA. VEGF has been shown to be the critical angiogenesis factor responsible for vascular proliferation and blood vessel invasion of the synovial lining membrane in RA. Acidic FGF (FGF-1) and basic FGF (FGF-2) have also been implicated in aberrant synoviocyte proliferation (i.e. synovial hyperplasia) and apoptosis resistance in adult RA.
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PMID:Growth hormone, VEGF and FGF: involvement in rheumatoid arthritis. 1689 35


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