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)

An adenocarcinoma of the second portion of the duodenum in a 26-year-old male is presented. The patient was suffering from pain in the epigastrium. Immunofluorescent studies revealed that it consisted almost exclusively of cells with a distincly positive somatostatin-like immunoreactivity. Ultrastructurally, the cytoplasm of the tumor cells had numerous large round granules (about 400 micrometers) with variable electron density. Most of these cells closely resembled the D cells normally seen in the duodenum and the islets of the pancreas, although a few argyrophil cells could be demonstrated by light microscopy. Radioimmunoassay of extracts of the tumor revealed a large amount of somatostatin (2260 pg/mg); substance P and VIP were detected also. Somatostatinoma has been known to occur in the pancreas, but this seems to be the first somatostatinoma found in the intestine.
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PMID:Somatostatinoma of the duodenum. 50 96

The innervation of lumbar facet capsule and ligamentum flavum was investigated using antisera to a general neuronal marker protein gene product (PGP) 9.5 and to peptide markers of sensory nerves (calcitonin gene-related peptide [CGRP] and substance P) and autonomic nerves (vasoactive intestinal polypeptide [VIP] and C-flanking peptide of neuropeptide Y [CPON]). In the facet capsule (n = 14), PGP 9.5 and CGRP-immunoreactive nerves occurred in 12 and five specimens, respectively, both around blood vessels and as free fibers in the stroma. Free fibers immunoreactive for substance P or VIP were noted in three and five specimens, whereas in nine specimens there were CPON-immunoreactive nerves located perivascularly. There was no immunoreactivity in the ligamentum flavum. This study provides further evidence that the facet capsule but not the ligamentum flavum has substantial innervation by sensory and autonomic nerve fibers and has a structural basis for pain perception.
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PMID:Morphological basis for back pain: the demonstration of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in ligamentum flavum. 153 Jul 99

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.
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PMID:Molecular anatomy of the neuro-immune connection. 177 30

1. Co-localization of SP and CGRP was observed in a dense intraepithelial and perivascular network of capsaicin-sensitive sensory nerves in the nasal mucosa of different species, including man. The morphological similarity in the distribution of these nerves among various experimental animals and man indicates that animal experimental data may be used for the understanding of sensory mechanisms in the human nasal mucosa. 2. Release of CGRP into the venous effluent of the nasal mucosa in parallel with vasodilatation was demonstrated in vivo upon antidromic stimulation of the maxillary division of the trigeminal nerve or local i.a. capsaicin injection. 3. Infusion of capsaicin induced concentration-dependent increase in arterial, venous and superficial blood flow as well as V in the pig nasal mucosa. Exogenous SP, CGRP and VIP displayed concentration-dependent, but partly separate, vasodilatory profiles in the nasal mucosa. SP was more potent regarding maximal blood flow increase, whereas the vasodilatation induced by CGRP infusion was more long-lasting on an equimolar basis. Although VIP caused an increase in ABF and VBF as well as V, the LDF signal (i.e. superficial blood flow) was decreased, possibly due to a stealing phenomenon. 4. Local i.a. capsaicin infusion induced a bilateral chlorisondamine-sensitive atropine-resistant vasodilatation. However, i.a. capsaicin in higher doses also induced a chlorisondamine-resistant vasodilatation in the superficial vascular compartment of the nasal mucosa, presumably via the release of sensory neuropeptides. Thus, the vasodilatory effect of capsaicin may be due to a complex interaction of local effects on the sensory nerve terminals close to blood vessels in the nasal mucosa and a main parasympathetic central reflex. 5. Capsaicin, but not nicotine, induced a concentration dependent increase in irritation or pain upon local application to the human nasal mucosa. Since both agents evoked secretion, this indicates that capsaicin and nicotine activate different populations of sensory neurons. Local application onto the nasal mucosa of capsaicin and nicotine as well as metacholine induced a concentration dependent muscarinic antagonist sensitive increase in the secretory response. The capsaicin or nicotine-induced secretion was bilateral and could be markedly reduced by combined pretreatment with a local anaesthetic and a vasoconstrictor. Our findings suggest that the secretory effect of capsaicin and nicotine in the human nasal mucosa is mediated via a central parasympathetic reflex arc with a final muscarinic receptor mechanism. No clear-cut contribution seemed to be exerted by locally released tachykinins and CGRP as direct trigger substances for the secretory response to capsaicin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sensory and motor reflex control of nasal mucosal blood flow and secretion; clinical implications in non-allergic nasal hyperreactivity. 189 72

The present study examines the effects of intrathecal administration of selected peptides on nociceptive responses in the rat. Each peptide was delivered via a chronically implanted catheter to the L5 vertebral level. In the tail flick test, VIP (0.65-6.5 nmoles) produced a dose-dependent decrease in reaction time (RT) from 1 to 6-16 min after injection; 6.5 nmoles decreased RT to 37% of control value at 1 min after injection. Galanin (0.65-6.5 nmoles) produced a dose-dependent increase in reaction time at 1 and 6 min; at high doses, many of the rats failed to flick the tail. CGRP (6.5 nmoles) produced a small, transient decrease in RT to 73% of control values at 1 min; 3.25 nmoles were without effect. CSF and 6.5 nmoles of somatostatin, TRH and angiotensin II were without effect. At high doses of galanin and CGRP, rats vocalized to innocuous touch of the tail, as reported for substance P. Von Frey hairs were thus applied to the tail after 6.5 nmoles of VIP, galanin, CGRP or substance P. Vocalization in response to a previously innocuous pressure stimulus was observed at 30 s after injection in all rats given galanin and some rats given CGRP or substance P; the effect lasted 4-8 min. VIP and CSF had no effect. These results suggest that VIP, galanin, CGRP and substance P may act as excitatory agents in nociceptive pathways and that specific peptides may function in the different types of pain modalities; VIP in thermal, galanin in mechanical and substance P and CGRP in both.
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PMID:Effects of intrathecal administration of neuropeptides on a spinal nociceptive reflex in the rat: VIP, galanin, CGRP, TRH, somatostatin and angiotensin II. 245 92

Hyperreflectory rhinopathy (HR) is a non-specific hyperreactivity of the nasal mucosa. It causes hypersecretion, decreased nasal patency, sneezing and sometimes headache by local reflexes, which are beyond voluntary control. The synonymous name "vasomotor rhinitis" or "vasomotor rhinopathy" is no longer adequate with regard to our present state of knowledge of the autonomous innervation of the human nasal mucosa. Recent pharmacological investigations show the great importance of peptidergic neurons. In our own studies, the presence and the topical effects of the neuropeptide substance-P in human nasal mucosa are examined. A new concept of the autonomous innervation of the human nasal mucosa is presented. Apart from adrenergic and cholinergic neurons, it also includes peptidergic neurons (SP, CGRP, NKA, VIP, PHI, APP, GRP). According to this model, a hypothesis on the pathogenesis of HR is developed. A key position is occupied by the so-called "axon reflex" which is mediated by substance-P immunoreactive nerve fibers. It is released by a chemical, thermal or mechanical irritation. This axon reflex mediates pain, vasodilation and plasma extravasation (neurogenic oedema), hypersecretion such as smooth muscle contraction, and sneezing reflex. Capsaicin (8-methyl-N-vanillyl-6-nonenamid) leads to a selective degeneration of substance-P immunoreactive nerve fibres and desensitisation of its receptors after repeated topical or systemic application, thus blocking the axon reflex. The risk-free application of capsaicin was shown in self-experiments and in volunteers. Our hypothesis was confirmed by the good results of the treatment of a group of volunteer patients who suffered from HR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New aspects in the pathogenesis and therapy of hyperreflexive rhinopathy]. 305 Mar 40

Calcitonin (CT) is a polypeptide hormone produced in the thyroid gland that regulates, blood calcium levels and bone calcium metabolism. The unexpected finding of binding sites for calcitonin in several areas of the brain oriented attention to activities of CT in the central nervous system and also to its antinociceptive action. The first report of this last effect was in 1975, and the many different experimental and clinical data on this topic reported since then are reviewed here. The heterogenous findings have been organized according to the logical classification of animal and human studies. For each of these headings, subheadings such as acute and chronic pain, different kinds of administration and different procedures used to record the results, are considered. The several proposed mechanisms of action, involving serotoninergic, catecholaminergic, Ca2+ fluxes, protein phosphorylation, beta-endorphin production, cyclooxygenase inhibition and histamine interference are also reviewed. Calcitonin, neurotensin, substance P, VIP and, recently, CGRP are some of the non-opioid peptides that have been reported to interfere with pain and that open up a new, alternative way of investigating antinociceptive drugs different than opioid or opioid-like agents. An examination of the state-of-investigation of calcitonin's antinociceptive activity in the last 17 years shows that many experimental studies indicate the existence of this effect, including studies in humans, and this opens up perspectives for therapy with a new class of antinociceptive agents.
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PMID:Calcitonin and its antinociceptive activity: animal and human investigations 1975-1992. 794 19

1. RR may act as a preferential capsaicin antagonist in the pig nasal mucosa in vivo. However, the present data reveal a narrow concentration range for the selective actions of RR. Moreover, RR has systemic cardiovascular side effects despite local i.a. infusion in the IMA. 2. Acoustic rhinometry is a useful method for investigations of changes in nasal cavity volume in the pig in vivo. 3. The NK1-receptor antagonist RP-67,580 lacks NK1-receptor blocking properties in the pig in vivo. In contrast, CP-96,345 and SR 140.333 significantly blocked SP-mediated vascular effects in the pig nasal mucosa and superficial skin, indicating species dependent NK1-receptor selectivity. Capsaicin-induced vasodilatation in the IMA was not attenuated after administration of CP-96,345 and SR 140.333 whereas the superficial blood flow in the nasal mucosa and skin was slightly reduced. The CGRP-receptor antagonist hCGRP 8-37 markedly reduced the capsaicin-evoked vascular effects in the pig nasal mucosa and superficial skin. 4. Vanilloid receptors, as revealed by 3H-RTX binding, are present in the pig nasal mucosa although with different characteristics compared to vanilloid receptors in the pig dorsal horn. Capsaicin, RTX and LA evoked vasodilatation in the pig nasal mucosa in a similar fashion, indicating activation of sensory nerves. The LA (proton)-evoked vasodilatation was significantly attenuated after local i.a. infusion of hCGRP 8-37, closely resembling the results obtained from the capsaicin challenge before and after CGRP-receptor blockade. Capsazepine did not reduce the capsaicin-and LA-evoked vasodilation in the pig nasal mucosa. This agrees well with the observation that capsazepine did not inhibit RTX binding to vanilloid receptors in pig nasal mucosal membranes. 5. Capsaicin desensitisation of the human nasal mucosa attenuated the subjective pain response as well as the reduction of the cross-sectional area in the nasal cavity evoked by LA and hypertonic saline. This finding gives further support to the hypothesis that protons may act as endogenous ligands to the vanilloid receptor also in man. 6. Systemic administration of the NOS inhibitor L-NNA significantly reduced basal nasal V Con and increased C Vol in the pig. The effects evoked by L-NNA were similar in magnitude to those of phenylephrine and UK 14304, although of much longer duration. Administration of L-NNA did not reduce the vasodilator responses to SP and ACh, suggesting that these substances may mediate their vascular effects via one or several other mechanisms beside the NO/cGMP pathway. Moreover, capsaicin-, VIP-, and nitroprusside-evoked vasodilatation was not reduced after NOS inhibition. 7. Heavy physical exercise and alpha-adrenoceptor agonists reduce nasal cavity NO levels acutely in man. This may be due to a reduced supply of substrates for NO synthesis in the paranasal sinus epithelium, the primary NO production site in the upper airways. However, prolonged use of the alpha 2-adrenoceptor agonist oxymetazoline for 10 days, did not reduce basal nasal cavity NO levels. Nasal cavity NO levels and C Vol were not altered after topical administration of the NOS inhibitor L-NAME. Nor did we see any change in C Vol after local challenge with NO gas in the nasal cavity. The present results indicate that the human nasal mucosa is largely insensitive to NO gas in contrast to the bronchial mucosa and lung. 9. In conclusion, the present results suggest that vanilloid receptors are present on sensory nerves in the pig nasal mucosa and that LA (protons) may act as an endogenous ligand to this receptor. Sensory neuropeptides, especially CGRP, may be of importance for nasal congestion upon sensory nerve activation. Hence, selective, non-peptide CGRP-receptor antagonists may be of potential use in nasal disorders characterised by nasal congestion. NO is of importance for basal nasal vascular regulation. However, whether NOS inhibitors have potential as useful nasal de
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PMID:Sensory neuropeptides and nitric oxide in nasal vascular regulation. 880 Mar 74

Intracavernous injection of vasodilators has been the greatest diagnostic and therapeutical breakthrough in erectile dysfunction (E.D.). After 15 years experience, these vasodilators have demonstrated efficacy rates over 85%. This suggests that most cases of E.D. are the result of and inability of the smooth muscle to relax. This paper presents an overview of the diagnostic and therapeutic use of intracavernous vasodilating drugs. It includes an extensive review of the literature and our personal series with regard to efficacy, indications, contraindications and side-effects of these compounds. Alprostadil i.c. injection (PGE1) is an effective (> 70%) and safe treatment, and its use has been accompanied by an increased quality of life of patients, with very few side effects. Currently, PGE1 is a first choice drug in the treatment of impotence. When no response is seen, or pain develops after PGE1 administration, a number of vasoactive compounds associations can be used instead (phentolamine + PGE1, papaverine + phentolamine, and papaverine + phentolamine + PGE1). The phentolamine + VIP association has shown encouraging results. Prior to prescribe IC treatment with vasoactive drugs it is necessary to conduct a basic diagnostic study, and advise the patient. If treatment is finally accepted, the performance of adequate training and detailed medical follow-up is crucial.
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PMID:[Treatment of erectile dysfunction using intracavernous pharmacotherapy]. 965 42

Membrane metalloendopeptidase EC 3.4.24.11 (Enkephalinase, neutral endopeptidase, NEP) is a cellular ectoenzyme, immunophenotypically identified as the leukocyte cluster of differentiation CD10 or CALLA (common acute lymphoblastic leukemia antigen). Immunological, biochemical and molecular biology techniques have identified tis cell membrane feature in various organs: brain, cardiovascular system, lung, placenta, kidney etc. The CD10 immunophenotype is a common feature of lymphoblasts in acute lymphoid leukemia not expressing the T- or B-markers. The enzymatic activity of CD10/NEP possibly influences normal lymphocyte ontogeny by proteolytic cleavage of the regulatory peptides. The substrates of CD10/NEP in the kidneys are (see the list of abbreviations) ANP, adrenomedullin and PAMP; in the brain, the substrates are enkephalins and oxytocin; in the lung, bombesin, BLP, GRP, neuromedin C, substance P and neurokinin A; in the cardiovascular system, angiotenisin II, bradykinin and CGRP; in the gut, VIP; on the neutrophil membrane, fMLP etc. Some substrates are not strictly tissue-specific, e.g. substance P. Preclinical and clinical trials explore possibilities of therapeutic application of the inhibitors of neutral endopeptidase, such as thiorphan in the management of pain, diarrhoea, depression, arterial hypertension and asthma. Other possibilities of application include the treatment of hyalinomembranous disease and prevention of neurotoxicosis in tetanus and botulism.
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PMID:[Membrane metalloendopeptidase (CD10/CALLA): distribution, physiologic and pathophysiologic functions and its inhibitors]. 974 92


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