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)

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

A range of substituted isothiourea compounds including S-isopropylisothiourea (IPTU), S-methylisothiourea (SMT), S-ethylisothiourea (ETU), N-pentylisothiourea (PTU), S-(2 aminoethyl)isothiourea (AETU), and S-acetamidoisothiourea (AATU) inhibit mouse spinal cord/cerebellar neuronal nitric oxide synthase (nNOS) and bovine aortic endothelial cell eNOS in vitro. IP administration of isothioureas increased mean arterial blood pressure of the urethane-anaesthetised mouse (rank order of effect: IPTU > ETU > SMT > AETU). PTU and AATU were without vasopressor activity. IPTU (50 mg/kg, IP) inhibited late phase formalin-induced hindpaw licking behaviour in the mouse while SMT (50 mg/kg, IP) was without effect. Neither compound influenced the formalin-induced increase in hindpaw weight reflecting a lack of significant peripheral antioedema effect in this model. IPTU (50 mg/kg, IP) but not SMT (50 mg/kg, IP) inhibited mouse spinal cord and cerebellar NOS activity measured ex vivo in animals killed 45 min after injection. The present study confirms the potent NOS inhibitory effect of selected substituted isothioureas in vitro. Little or no isoform selectivity (i.e., nNOS vs. eNOS) was apparent. The potent vasopressor effect of isothioureas indicates that these compounds may be of limited use as tools to study the role of nitric oxide in pain perception.
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PMID:Inhibition of nitric oxide synthase by isothioureas: cardiovascular and antinociceptive effects. 895 52

Nitric oxide (NO) is an important inflammatory mediator in nonhuman animal models of rheumatoid arthritis (RA). The purpose of the present study was to determine whether blood mononuclear cells from patients with active RA (as compared to control subjects) have higher levels of NO synthase type 2 (NOS2) and produce more NO in vitro. Leukocytes from 25 RA patients and 20 normal subjects were examined. Arthritis activity was assessed by tender and swollen joint counts, duration of morning stiffness, patient assessment of pain, physician and patient global assessment of disease activity, the modified Stanford Health Assessment Questionnaire, and by blood levels of acute phase reactants. Blood mononuclear cell NOS enzyme activity/antigen content and nitrite/nitrate formation in vitro were measured. Blood mononuclear cells from RA patients had increased NOS activity and increased NOS2 antigen content as compared to those from normal subjects, and responded to interferon-gamma with increased NOS expression and nitrite/nitrate production in vitro. NOS activity of freshly isolated blood mononuclear cells correlated significantly with disease activity, as assessed by render and swollen joint counts. Our results demonstrate that patients with RA have systemic activation for NOS2 expression, and that the degree of activation correlates with disease activity. Increased NOS2 expression and NO generation may be important in the pathogenesis of RA.
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PMID:Increased expression of blood mononuclear cell nitric oxide synthase type 2 in rheumatoid arthritis patients. 906 35

Opioids relieve painful stimuli by interacting with the opioid receptor subtypes, mu, delta, and kappa, in brain regions and spinal cord. Tolerance reduces medication effectiveness and causes a right-hand shift in the dose-response curve. The mechanisms involved in the development of opioid tolerance remain not clear. Following long-term opioid treatment, either a decrease or increase in opioid receptors was demonstrated, depending on the types or subtypes of receptors and the central areas to which they are distributed. Opioid receptors, like most other hormone and neurotransmitter receptors, have been shown to mediate their effects through guanine nucleotide binding protein (G protein). Studies regarding chronic treatment with opioid agonists suggest that the uncoupling of the opioid receptors from their corresponding G protein may play an important role in opioid tolerance. The NMDA (N-methyl-D-aspartate) receptors have also been demonstrated involving not only in nociception and pain processing but also in the development of opioid tolerance. The sustained potentiation of NMDA receptor-mediated responses may be provided through activation of PKC (protein kinase C). Furthermore, NMDA receptor-mediated intracellular translocation and activation of PKC may be a critical step in the development of opioid tolerance. The NMDA receptors can also induce the synthesis of NO (nitric oxide) through the activation of NOS (NO synthase). NOS inhibitors were also shown to prevent the development of opioid tolerance, therefore, NO was suggested to play a role in opioid tolerance development. Although much evidence indicates the reasons of opioid tolerance, it is still worth further investigation to explore the mechanisms of multiplicity of opioid receptors and complexity of intracellular biochemical events.
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PMID:[Cellular mechanism of opioid tolerance]. 908 51

Nitric oxide (NO) is a neuronal messenger that it is thought to be involved in the nociceptive transmission modulation. The activity of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) was shown to be identical to NOS activity in the brain. Since the periaqueductal gray matter (PAG) plays an important role in pain perception and antinociception this study was carried out to monitor the expression of NADPH-d in PAG after nociceptive visceral stimulation. Our data showed that the noxious visceral stimulation significantly increased NADPH-d positive neurons and that these neurons were localized in the ventrolateral areas of the PAG. These findings suggest that NO in the PAG may play a role in pain modulation and antinociception.
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PMID:Induction of NADPH-diaphorase activity in the rat periaqueductal gray matter after nociceptive visceral stimulation. 963 Jul 10

Prospective data on 1,360 consecutive inpatients referred to the consultation-liaison psychiatry service of 2 metropolitan general teaching hospitals and diagnoses as having a Depressive Illness Spectrum Disorder were collected by using the MICRO-CARES clinical database system. The distribution of DSM-III-R diagnoses was major depression (MD) 49%; dysthymia (DYS) 15%; organic or substance-induced mood disorder or depressive disorder not otherwise specified (ORG/NOS) 14%; and adjustment disorder with depressed mood (AD) 29%s. Antidepressants were prescribed in 59% of the MD cases, 40% of the DYS cases, 36% of the ORG/NOS cases, and 17% of the AD cases. In confirmed MD, antidepressants were prescribed in 69%, and significantly more often in those who were older, female, had a prior history of physical illness, had a neoplasm or a disorder of the nervous or musculoskeletal systems, had higher Axis IV scores, or were referred because of pain or terminal illness. The patients with confirmed MD prescribed antidepressants had a longer length of stay and were referred later than those not prescribed antidepressants. The results illustrate the importance of all the forms of depression in consultation-liaison psychiatry and the vigor with which all forms are treated.
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PMID:Consultation-liaison psychiatrists management of depression. 966 71

The possibility nitric oxide (NO) is involved the neurodegenrative mechanisms in the spinal cord following a chronic peripheral nerve lesion was examined using NOS immunohistochemistry. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model, a model of neuropathic pain and rats were allowed to survive for 8 weeks. In one group of animals L-NAME was given intraperitoneally (1-2 mg/kg, i.p. daily) for 6 weeks. Sham operated rats, in which the spinal nerve was exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of NOS which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, ultrastructural investigations showed distorted neurons, membrane disruption and myelin vesiculation. Sham operated rats did not show either NOS upregulation or structural changes in the spinal cord. Pretreatment with L-NAME significantly reduced NOS upregulation and the structural changes in the spinal cord were less pronounced. These observations strongly indicate a putative role of NOS in the pathophysiology of chronic nerve lesion. Our results may provide a new strategy to treat chronic neuropathic pain or to minimise neurodegeneration in the patients suffering from such diseases of the nervous system.
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PMID:Spinal nerve lesion induces upregulation of neuronal nitric oxide synthase in the spinal cord. An immunohistochemical investigation in the rat. 987 49

The survey involved 50 centres comprising both hospital and community psychiatric care services throughout Italy. Overall, 2620 patients were recruited, and of those 2002 (76%) completed the Somatoform Disorders Schedule (SDS), a CIDI-derived interview. The NOS somatoform disorders (SDs) diagnosis appeared to be the most common (60%) (and they showed the highest number of co-morbid diagnoses), followed by pain disorders (8%). The prevalence of undifferentiated somatoform and hypochondriactal disorders was 1.6%: older age groups showed a tendency towards higher rates of the latter. In general, the study found that a significant percentage of patients with SDs are referred to psychiatric services, but mainly because of other psychopathological problems: in fact, somatic complaints are cross-sectionally present in different psychiatric nosological categories. This study also emphasizes some limitations of the current classification of SDs.
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PMID:Prevalence of somatoform disorders in a psychiatric population: an Italian nationwide survey. Italian Collaborative Group on Somatoform Disorders. 992 3

Prostaglandins, metabolites of arachidonic acid, released during tissue injury and inflammation sensitize primary afferent nociceptors. While it has been suggested that this effect on nociceptors is mediated mainly via the cAMP second messenger system, recent evidence suggests that nitric oxide (NO) is also involved in peripheral pain mechanisms. To test the hypothesis that NO contributes to the sensitization of nociceptors to mechanical stimuli induced by hyperalgesic prostaglandins, we compared von Frey hair mechanical threshold as well as the response evoked by 10-s sustained threshold mechanical stimulation before and after injection of prostaglandin E2 (PGE2) alone, and NOS inhibitor NG-methyl-L-arginine (L-NMA) or its inactive stereoisomer NG-methyl-D-arginine (D-NMA) plus PGE2, adjacent to the receptive field of C-fiber nociceptors. The reduction of mechanical threshold and increase in number of action potentials to sustained mechanical stimulation induced by intradermal application of PGE2 was blocked by L-NMA, but not D-NMA. It is suggested that NO contributes to nociceptor sensitization induced by hyperalgesic prostaglandins.
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PMID:NOS inhibitor antagonism of PGE2-induced mechanical sensitization of cutaneous C-fiber nociceptors in the rat. 1008 24

The efficacy of the inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine hydrochloride (L-NMMA), was tested in 16 patients with chronic tension-type chronic headache. The study was designed as a randomized double-blind, crossover trial. Patients were assigned intravenous infusion of 6 mg/kg L-NMMA or placebo on two days separated by at least one week in a randomized order. Headache intensity was measured on a 100 mm visual analogue scale at baseline and at 30 min, 60 min, and 120 min after start of treatment. L-NMMA reduced pain intensity significantly more than placebo: 120 min after start of treatment, the mean pain score was decreased from 49 to 33 with L-NMMA and from 44 to 40 with placebo (p = 0.01). The present study demonstrates that inhibition of NOS has an analgesic effect in chronic tension-type headache.
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PMID:[Inhibition of nitric oxide synthase has an analgesic effect in chronic pain]. 1064 15


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