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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impairment of endothelial function in hypercholesterolaemic animals and humans is known to be reversed by intravenous infusions of L-arginine (L-ARG), the precursor of NO. 22 patients with peripheral arterial obstructive disease (PAOD) received L-ARG (60 mmol) as intravenous infusions, each lasting three hours, daily for seven consecutive days. This treatment resulted in elongation of the painfree and maximum walking distances, as well as shortening of the period of time required for pain relief after walking the maximum distance. A rise in the ankle/arm pressure ratio (AAPR) was associated with an increase of arterial blood flow in both calves. The transcutaneous oxygen tension (tcpO2) in the ischaemic foot was also increased. After the 1st and the 7th infusion of L-ARG the spontaneous (PAR) as well as the ADP- and collagen-induced platelet aggregation were suppressed, the euglobulin clot lysis time (ECLT) shortened, plasma levels of platelet activator inhibitor (PAI) decreased, and cGMP levels increased. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with PAOD. We presume that in these patients high doses of exogenous L-ARG can be partially converted to NO.
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PMID:Treatment with L-arginine is likely to stimulate generation of nitric oxide in patients with peripheral arterial obstructive disease. 886 84

This study explored the relationship between malocclusion and signs and symptoms of temporomandibular disorders (TMD) in 124 patients with severe Class II malocclusion, before and 2 years after bilateral sagittal split osteotomy (BSSO). Patients were evaluated with the Craniomandibular Index (CMI), the Peer Assessment Rating Index (PAR Index, to assess gross changes in the occlusion), and symptom questionnaires. The results showed a significant improvement in occlusion; PAR Index scores dropped from a mean of 18.1 before surgery to a mean of 6.1 at 2 years postsurgery (P < 0.001). The CMI and masticatory index (MI) for muscle pain indicated clinically small but statistically significant improvement (P = 0.0001) from before surgery (mean CMI = 0.14, mean MI = 0.15) to after surgery (mean CMI = 0.10, mean MI = 0.08). The number of patients with clicking upon opening decreased significantly from 33 (26.6%) to 13 (10.5%) (P = 0.001). However, the number of patients with fine crepitus increased from 5 (4.0%) before surgery to 16 (12.9%) at 2 years postsurgery (P = 0.005). Significant reductions in subjective pain and discomfort were also found 2 years after surgery. The magnitude of change in muscular pain was not related to the severity of the pretreatment malocclusion, a finding that suggests that factors other than malocclusion may be responsible for the change in TMD.
J Orofac Pain 1998
PMID:Effects of major Class II occlusal corrections on temporomandibular signs and symptoms. 978 Sep 39

The purposes of this study were to determine the relationship between the physical activity values obtained from the peripheral arterial disease-physical activity recall (PAD-PAR) questionnaire and (1) the free-living daily physical activity obtained from the doubly labeled water technique and (2) clinical measures of PAD severity. Fifty-one older PAD patients (age= 70 +/- 6 years) were recruited from the Vascular Clinic at the Baltimore Veterans Affairs Medical Center and from radio and newspaper advertisements. Energy expenditure of physical activity (EEPA) was determined by using doubly labeled water and indirect calorimetry techniques. PAD severity was measured by ankle/brachial index (ABI) and walking distance to maximal claudication pain determined during a graded treadmill test. In addition, patients were also characterized on body composition and total daily energy expenditure. The physical activity values obtained from the PAD-PAR questionnaire (113 +/- 37 MET-hr/wk) were not related to EEPA (542 +/- 260 kcal/day; r= -0.057, p=0.690), ABI (0.64 +/- 0.19; r=0.032, p=0.826), or distance to maximal claudication pain (376 +/- 229 m; r=-0.054, p=0.731). The authors conclude that the PAD-PAR questionnaire is not an accurate measurement of free-living daily physical activity when compared to EEPA by use of the criterion method of doubly labeled water, and the activity questionnaire measures were poorly correlated with clinical measures of PAD severity.
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PMID:Relationship between physical activity recall and free-living daily physical activity in older claudicants. 1074 5

PARs (protease-activated receptors) are a family of four G-protein-coupled receptors for proteases from the circulation, inflammatory cells and epithelial tissues. This report focuses on PAR(2), which plays an important role in inflammation and pain. Pancreatic (trypsin I and II) and extrapancreatic (trypsin IV) trypsins, mast cell tryptase and coagulation factors VIIa and Xa cleave and activate PAR(2). Proteases cleave PAR(2) to expose a tethered ligand that binds to the cleaved receptor. Despite this irreversible activation, PAR(2) signalling is attenuated by beta-arrestin-mediated desensitization and endocytosis, and by lysosomal targeting and degradation, which requires ubiquitination of PAR(2). beta-Arrestins also act as scaffolds for the assembly of multi-protein signalling complexes that determine the location and function of activated mitogen-activated protein kinases. Observations of PAR(2)-deficient mice support a role for PAR(2) in inflammation, and many of the effects of PAR(2) activators promote inflammation. Inflammation is mediated in part by activation of PAR(2) in the peripheral nervous system, which results in neurogenic inflammation and hyperalgesia.
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PMID:Protease-activated receptor 2: activation, signalling and function. 1464 Oct 24

The role of protease activated receptor-2 (PAR-2) activation in trigeminal nociception and in induction of functional competence in the delta opioid receptor (DOR) is not known. In this study, we evaluated whether agonists of PAR-2 activate the capsaicin-sensitive subclass of trigeminal nociceptors in a PLC-PKC-dependent manner and induce functional competence in the DOR. Adult male rat trigeminal ganglion (TG) cultured neurons were treated with the PAR-2 agonist (SL-NH2) or an enzyme activator of PAR (trypsin) and the activation of TG nociceptors was assessed using three independent methods: neuropeptide release, calcium influx, and whole cell patch-clamp. The specificity of SL-NH2 and trypsin responses was evaluated using TG cultures transfected with siRNA against PAR-2. The in vivo role of PAR-2 activation was determined measuring SL-NH2 and trypsin-evoked nocifensive behavior and increase in blood flow. Trigeminal neurons were treated with SL-NH2/vehicle and then the DOR agonist to determine DOR inhibition of evoked neuropeptide release and cAMP accumulation. The results showed that SL-NH2 (100 microM) and trypsin (1-600 nM) activate TG nociceptors, which is partly reversible by the PKC inhibitor bisindolylmaleimide (500 nM) and by ruthenium red (10 microM). In cultures treated with siRNA against PAR-2, both SL-NH2 and trypsin responses were significantly diminished. Both SL-NH2 and trypsin evoke nocifensive behavior and increases in blood flow in an orofacial pain model. Application of SL-NH2 rapidly produced functional competence of DOR for inhibiting nociceptor function. In inflamed tissue, endogenous proteases may activate TG nociceptors and generate pain. Moreover, activation of PAR-2 can also induce functional competence in DOR.
Pain 2006 Nov
PMID:PAR-2 agonists activate trigeminal nociceptors and induce functional competence in the delta opioid receptor. 1678 Oct 76

Agonists of protease-activated receptor 2 (PAR(2)) evoke hyperexcitability of dorsal root ganglia (DRG) neurons by unknown mechanisms. We examined the cellular mechanisms underlying PAR(2)-evoked hyperexcitability of mouse colonic DRG neurons to determine their potential role in pain syndromes such as visceral hyperalgesia. Colonic DRG neurons were identified by injecting Fast Blue and DiI retrograde tracers into the mouse colon. Using immunofluorescence, we found that DiI-labelled neurons contained PAR(2) immunoreactivity, confirming the presence of receptors on colonic neurons. Whole-cell current-clamp recordings of acutely dissociated neurons demonstrated that PAR(2) activation with a brief application (3 min) of PAR(2) agonists, SLIGRL-NH(2) and trypsin, evoked sustained depolarizations (up to 60 min) which were associated with increased input resistance and a marked reduction in rheobase (50% at 30 min). In voltage clamp, SLIGRL-NH(2) markedly suppressed delayed rectifier I(K) currents (55% at 10 min), but had no effect on the transient I(A) current or TTX-resistant Na(+) currents. In whole-cell current-clamp recordings, the sustained excitability evoked by PAR(2) activation was blocked by the PKC inhibitor, calphostin, and the ERK(1/2) inhibitor PD98059. Studies of ERK(1/2) phosphorylation using confocal microscopy demonstrated that SLIGRL-NH(2) increased levels of immunoreactive pERK(1/2) in DRG neurons, particularly in proximity to the plasma membrane. Thus, activation of PAR(2) receptors on colonic nociceptive neurons causes sustained hyperexcitability that is related, at least in part, to suppression of delayed rectifier I(K) currents. Both PKC and ERK(1/2) mediate the PAR(2)-induced hyperexcitability. These studies describe a novel mechanism of sensitization of colonic nociceptive neurons that may be implicated in conditions of visceral hyperalgesia such as irritable bowel syndrome.
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PMID:Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon. 1728 84

The aim of this study was to assess the effect of patellar taping of the proprioceptive status of patients with patellofemoral pain syndrome (PFPS). A total of 32 subjects (18 males, 14 females of age 31.9 +/- 11.2, body mass index 25.8 +/- 5.3) with PFPS were tested for Joint Position Sense (JPS) using a Biodex dynamometer. Outcomes of interest were the absolute error (AE), the variable error (VE) and the relative error (RE) of the JPS values for both active (AAR) and passive (PAR) angle reproduction at an angular velocity of 2 degrees /s with a start angle at 90 degrees and target angles of 60 degrees and 20 degrees . Taping was applied in random order across the patella of each subject with each of the subjects acting as their own internal control. Results indicated initially that application of patellar tape did not enhance and in some cases worsened the JPS of the subjects (P > 0.05). However, when the subjects' proprioceptive status was graded according to their closeness to the target angles into 'good' (5 degrees , N = 10) and 'poor' ( > 5 degrees , N = 22) taping enhanced nearly all values of those with 'poor' proprioception, with AE at 20 degrees to statistical significance (P = 0.021). In conclusion, this study has shown that patellar taping did not improve the AAR and PAR JPS tests of a whole sample of 32 PFPS patients. It also has shown that a subgroup of PFPS patients with poor proprioception may exist and be helped by patellar taping.
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PMID:Effects of patellar taping on knee joint proprioception in patients with patellofemoral pain syndrome. 1729 23

Peripheral diabetic neuropathy is a heterogeneous group of disorders, and is known to affect 50-60% of diabetic patients. Poly (ADP-ribose) polymerase (PARP) activation has been identified as one of the key components in the pathogenesis of diabetic neuropathy. In the present study we have targeted PARP overactivation in diabetic neuropathy using a known PARP inhibitor, 4 amino 1, 8-napthalimide (4-ANI). Streptozotocin induced diabetic rats developed neuropathy within 6 weeks, which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) along with neuropathic pain and abnormal sensory perception. Six weeks after diabetes induction Sprague Dawley rats were treated with 4-ANI (3 and 10 mg/kg, p.o.) for a period of two weeks (seventh and eighth weeks). Two week treatment with 4-ANI showed improvement in nerve conduction, nerve blood flow and reduction in tail flick responses and mechanical allodynia in diabetic animals. 4-ANI also attenuated PAR immunoreactivity and NAD depletion in nerves of diabetic animals. Results of present study suggest the potential of PARP inhibitors like 4-ANI in the treatment of diabetic neuropathy.
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PMID:Protective effects of 4-amino1,8-napthalimide, a poly (ADP-ribose) polymerase inhibitor in experimental diabetic neuropathy. 1826 71

The present study investigated whether combination of resveratrol and 4-amino 1,8 naphthalimide (4-ANI) is effective in the development of diabetic neuropathy (DN). After 6 weeks of diabetes induction, rats were treated for 2 weeks with resveratrol and 4-amino 1,8 naphthalimide (4-ANI) either alone or in combination. Experimental end points included functional, behavioural and biochemical parameters along with PAR immunohistochemistry and were performed at the end of treatment. Combination of resveratrol (10 mg/kg) and 4-ANI (3 mg/kg) attenuated conduction and nerve blood flow deficits and resulted in amelioration of diabetic neuropathic pain. Significant reversal of biochemical alterations (peroxynitrite, MDA and NAD levels) were also observed, as well as PAR accumulation in the sciatic nerve. This study suggests the beneficial effect of combining resveratrol and 4-ANI in experimental diabetic neuropathy.
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PMID:Neuroprotective potential of combination of resveratrol and 4-amino 1,8 naphthalimide in experimental diabetic neuropathy: focus on functional, sensorimotor and biochemical changes. 1929 93

Protease-activated receptor-4 (PAR(4)) belongs to the family of receptors activated by the proteolytic cleavage of their extracellular N-terminal domain and the subsequent binding of the newly released N-terminus. While largely expressed in the colon, the role of PAR(4) in gut functions has not been defined. We have investigated the effects of PAR(4) agonist on colonic sensations and sensory neuron signalling, and its role in visceral pain. We observed that a single administration of the PAR(4) agonist peptide (AYPGKF-NH(2)), but not the control peptide (YAPGKF-NH(2)) into the colon lumen of mice significantly reduced the visceromotor response to colorectal distension at different pressures of distension. Further, intracolonic administration of the PAR(4) agonist, but not the control peptide, was able to significantly inhibit PAR(2) agonist- and transcient receptor potential vanilloid-4 (TRPV4) agonist-induced allodynia and hyperalgesia in response to colorectal distension. Protease-activated receptor-4 was detected in sensory neurons projecting from the colon, and isolated from the dorsal root ganglia, where it co-expressed with PAR(2) and TRPV4. In total sensory neurons, PAR(4) agonist exposure inhibited free intracellular calcium mobilization induced by the pro-nociceptive agonists of PAR(2) and TRPV4. Finally, PAR(4)-deficient mice experienced increased pain behaviour in response to intracolonic administration of mustard oil, compared with wild-type littermates. These results show that PAR(4) agonists modulate colonic nociceptive response, inhibit colonic hypersensitivity and primary afferent responses to pro-nociceptive mediators. Endogenous activation of PAR(4) also plays a major role in controlling visceral pain. These results identify PAR(4) as a previously unknown modulator of visceral nociception.
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PMID:Protease-activated receptor-4 (PAR 4): a role as inhibitor of visceral pain and hypersensitivity. 1980 83


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