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)

In lightly-anesthetized dogs, ionic or non-ionic RCM (Iotalamato and iohexol, respectively) when injected by intracarotid route (i.c.), elicit a pain response comparable to that caused by bradykinin (BK) or capsaicin (CAP). This response, which is characterized by vocalization, hyperpnea, bradycardia and neck muscle contraction, was dose dependent and related to the osmolarity of the RCM. In the present study we observed that indomethacin did not interfere with CAP and RCM-induced pain at dose (2 mg/kg i.c.) that reduced BK-elicited responses. In contrast, Ruthenium Red (RR), in dose (1 mg/kg i.c.) that reduced CAP and/or RCM-induced effects did not affect BK-induced phenomena. We also verified that L-NAME (50 mg/kg i.c.) reduced the BK-, but not the CAP- and/or RCM-induced pain responses which suggests that an L-arginine-derived NO or related compound is involved in BK activation of perivascular nociceptors. Indeed, we found that i.c. injection of 20 mg of S-nitrosocysteine, a putative EDRF, caused BK-like responses. On the other hand, RCM and CAP appear to activate the same RR sensitive ionic channels of primary afferent endings. Therefore, RR-analogues could constitute a novel approach to minimizing or eventually abolishing the RCM side effects.
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PMID:Mechanism of pain induced by radiocontrast media. 128 41

A Japanese patient with systemic amyloidosis associated with a transthyretin (TTR) variant Arg50 is presented. This 41-year-old man became impotent and developed decreased pain sensation in his hands, and then sensory loss and muscle wasting in his lower legs, and cardiomyopathy appeared. The symptoms progressed and he died of congestive heart failure at age 46. There were amyloid deposits in all organs studied and massive amyloid deposition was seen in the peripheral nerves and cardiac muscles. Amyloid fibrils extracted from heart tissue contained TTR. A genetic mutation, causing a Ser50-->Arg substitution of the TTR molecule, was identified in another family member. Plasma TTR was shown to be a mixture of normal TTR Ser50 and mutant TTR Arg50 in the 2 subjects.
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PMID:Amyloid polyneuropathy with transthyretin Arg50 in a Japanese case from Osaka. 133 38

The Asu-AVT (1,6-aminosuberic acid -8-arginine-vasotocin) in an analogue of 8-arginine-vasotocin (AVT) which is one of pineal hormones. The effect of Asu-AVT on the pain threshold and EA analgesia was studied in rats. An increase of 16.2-41.5% in pain threshold was observed within 70 min. after ivc of Asu-AVT (75ng), while the Asu-AVT injection in combination with EA produced a significant increase of 164.6-309.1% in pain threshold, which was much higher than that in the saline-EA group (p < 0.05-0.01). The effect of Atu-AVT is analogous to that of oxytocin and arginine-vasopressin. The data indicate ivc of ASu-AVT not only elevates the pain threshold, but also enhances the EA analgesia. These results suggest that the pineal hormone, AVT may play a role in the EA analgesia.
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PMID:[Effect of Asu-AVT on electroacupuncture (EA) analgesia]. 133 26

We showed the intrinsic effects of the bradykinin (BK) receptor antagonists, NPC 567 (D-Arg-[Hyp3,D-Phe7]BK) and NPC 349 (D-Arg-[Hyp3,Thi5,8,D-Phe-7]BK), in the skin of humans. NPC 567 and NPC 349 caused dose-dependent pain, wheal, and flare on intracutaneous injection. After bradykinin, only the pain, but not the wheal and flare reactions were dose-dependent. The intravenous application of antihistamines (dimetidinmaleate and ranitidine) had little effect on pain intensity and reduced both wheal and flare response to the antagonists but not to bradykinin. We conclude that NPC 567 and NPC 349 have pain-evoking and histamine-releasing properties in the skin of humans which may limit their therapeutic and experimental use.
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PMID:Pain and inflammation evoked in human skin by bradykinin receptor antagonists. 138 8

1. L-NG-nitro arginine methyl ester (L-NAME) administered i.p. produces anti-nociception in the mouse assessed by the formalin-induced paw licking and acetic acid-induced abdominal constriction models. The non-steroidal anti-inflammatory drug (NSAID), flurbiprofen, was similarly anti-nociceptive in both models. 2. Combination of a sub-threshold dose of L-NAME (10 mg kg-1) with increasing doses of flurbiprofen (25- 75 mg kg-1) or a sub-threshold dose of flurbiprofen (50 mg kg-1) with increasing doses of L-NAME (10- 100 mg kg-1) resulted in potentiated anti-nociception in the formalin model. Combined therapy with sub-threshold doses of L-NAME (10 mg kg-1) and indomethacin (10 mg kg-1) also resulted in significant anti-nociception. In addition, combining sub-threshold doses of L-NAME (12.5 mg kg-1) and flurbiprofen (2 mg kg-1) significantly reduced acetic acid-induced abdominal constriction. 3. L-NAME (10 mg kg-1) administered i.p. caused a significant (approximately 35%) increase in MAP in the urethane-anaesthetized mouse. Flurbiprofen (50 mg kg-1) was inactive. Combination treatment with L-NAME (10 mg kg-1) and flurbiprofen (50 mg kg-1) failed to elevate MAP above that observed with L-NAME alone. Neither L-NAME (10 mg kg-1) nor flurbiprofen (50 mg kg-1) either alone or in combination significantly altered mouse locomotor activity. 4. These results suggest that L-NAME and flurbiprofen/indomethacin act synergistically in their anti-nociceptive action in the mouse. Combination therapy with L-NAME and flurbiprofen and a similar NSAID may provide an alternative to the clinical control of pain in man.
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PMID:Synergistic anti-nociceptive effect of L-NG-nitro arginine methyl ester (L-NAME) and flurbiprofen in the mouse. 139 74

Recent evidence has shown that activation of the N-methyl-D-aspartate receptor mediates the thermal hyperalgesia produced in a model of neuropathic pain. As the acute nociceptive effects of N-methyl-D-aspartate have been reported to be mediated through production of nitric oxide and activation of soluble guanylate cyclase, these experiments were designed to determine whether the thermal hyperalgesia produced in a rat model of neuropathic pain is also mediated through the production of nitric oxide and activation of soluble guanylate cyclase. Loose ligation of the sciatic nerve with chromic gut sutures, but not bilateral sham rats, demonstrated evidence of a marked thermal hyperalgesia on day 3 post-surgery. In bilateral sham rats, intrathecal administration of either an alternate substrate for nitric oxide synthase, NW-nitro-L-arginine methyl ester, or the soluble guanylate cyclase inhibitor, Methylene Blue, did not produce any change in thermal nociceptive withdrawal latencies. These same treatments blocked the thermal hyperalgesia in rats with chromic gut ligatures for a period of 2 and 4 h, respectively. These results suggest that a sustained production of nitric oxide and subsequent activation of soluble guanylate cyclase in the lumbar spinal cord mediate the thermal hyperalgesia produced in a model of neuropathic pain in the rat.
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PMID:Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat. 140 61

Four analogues of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, a mammalian FMRFamide-like peptide with antiopiate properties, were synthesized with N-terminus modifications and were shown to have high affinity for F8Famide binding sites. The degradation rate of these analogues in mouse brain slices was 3 times lower than that of the natural peptide. One analogue, (2DME)Y8Fa (D.Tyr-D.Leu-[N-Me]Phe-Gln-Pro-Gln-Arg-Phe-NH2), produced a clear hyperalgic effect and inhibited morphine analgesia in the mouse tail-flick test at lower doses than did the parent compound. (3D)Y8Fa (D.Tyr-D.Leu-D.Phe-Gln-Pro-Gln-Arg-Phe-NH2) and (2D)Y8Fa (D.Tyr-D.Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) in contrast did not decrease morphine analgesia but were analgesic alone. The analgesic effects of 22 nmol (2D)Y8Fa and (3D)Y8Fa were decreased by (1DME)Y8Fa (D.Tyr-Leu-[N-Me]Phe-Gln-Pro-Gln-Arg-Phe-NH2) or (2DME)Y8Fa and were reversed by naloxone. These results indicate opioid modulating properties of F8Famide. These analogues may prove to be useful tools for studying the modulation of pain by F8Famide.
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PMID:Analogues of F8Famide resistant to degradation, with high affinity and in vivo effects. 146

The pharmacokinetics and the relative bioavailability of a soluble granular form (sachets) of a pharmaceutical formulation containing ibuprofen (CAS 15687-27-1) and 1-arginine were investigated in healthy volunteers. Two granular dosage forms were evaluated, 200 and 400 mg, in comparison with the commercial equivalents (tablets). After the oral administration of both granular dosage forms, a quicker absorption and a significantly higher plasma bioavailability of ibuprofen in the first hour following the treatment than after tablets administration were observed. The mean values of peak plasma concentration (microgram/ml) were 26.1 and 56.4 after treatment with 200 and 400 mg sachets respectively vs. 16.3 and 43.0 after treatment with 200 and 400 mg tablets. The mean values of peak time were 16.9 and 24.4 min after treatment with 200 and 400 mg sachets respectively vs. 90.0 and 63.7 min after treatment with 200 and 400 mg tablets. The shortening in the absorption time and the increase in the plasma concentrations did not involve a quicker drug elimination nor cause any changes in the bioavailability (mean values of the relative bioavailability indexes of 0.98 for 200 mg dosage form and 1.02 for the 400 mg one). The analgesic activity of soluble ibuprofen 400 mg was compared with that of ibuprofen 400 mg tablets in patients with osteo-articular pain, according to a single dose, double-blind cross-over balanced design. The results showed that the soluble granular form is able to determine an analgesic effect significantly quicker and higher than that of tablets.
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PMID:Activity and pharmacokinetics of a new oral dosage form of soluble ibuprofen. 164 82

In order to understand the role of substance P (SP) in the brain and the relationship between SP and enkephalins in the electroacupuncture analgesia (EA), we have observed the influence of SP-antagonist, (D-Arg', D-Phe5, D-Trp7.9, Leu11) -SP (DADPDTL) injected intracerebroventricularly (icv) on EA and the change of the level of SP in the brain regions of the rat during EA. We have made a further observations on the influences of the naloxone (NX) on the che change of the content of SP induced by EA and DADPDTL on the increase in Leu-enkephalins (LEK) induced by EA. The Wistar rats were used in the experiment. The latency of the tail flick, immersing the tip of rat tail (4 cm) into hot-water of 50 degrees C, was taken as the pain threshold. The drugs were injected icv via plastic cannulae implanted in the bilateral ventricles. The EA was applied to the point of "Zusanli" (S36). The contents of SP and LEK were determined radioimmunoassay in the hypothalamus, mid-brain, striatum and pons-medulla-oblongata. The pain threshold was increased by 48 +/- 9% (P less than 0.01) after EA. But icv injection of DADPDTL decreased the pain threshold by 14 +/- 7% after EA. The result suggests that DADPDTL can antagonize the effect of EA and that SP in the brain is involved in EA. After EA the contents of SP in the hypothalamus and mid-brain of the rats were decreased by 29% and 28% in comparison with that of the control group respectively (both of them, P less than 0.05), but the contents of SP in the striatum and pons-medulla-oblongata had no significant change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of substance P in electroacupuncture analgesia and its relation to enkephalins in the rat brain]. 170 61

Previous work from this laboratory has provided biochemical characterization of several posttranslational processing intermediates of the neuropeptide substance P (SP) in central nervous system (CNS) tissues, including the COOH-terminal glycine-extended dodecapeptide Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-Gly (SP-G). SP-G is a major species of unprocessed SP found in rodent CNS tissues, and is the likely immediate precursor form of SP in the biosynthetic scheme. Here we present extensive characterization of the normal regional distribution of SP-G, as compared to SP, throughout the rat CNS via coordinated biochemical and morphological analyses. By radioimmunoassay (RIA), an approximate 10-fold variation in regional levels of SP-G-like immunoreactivity (SP-G-LI) was observed, ranging from 0.30 pmol/g in the amygdala, to 6.49 pmol/g in the medulla. On a normalized basis, the regional variation of unamidated precursor relative to mature peptide (SP-G-LI/SP-LI molar ratio) ranged from 0.30% in the amygdala to 5.15% in the dorsal root ganglia (DRG). Overall, the highest SP-G-LI/SP-LI ratios were found in DRG, medulla, and spinal cord, i.e. CNS areas associated with primary sensory afferent innervation via capsaicin-sensitive unmyelinated small diameter fibers. In addition, chromatographic and RIA analyses of extracted brain tissues indicated that the quantified immunoreactivities corresponding to SP, SP-G, as well as an additional COOH-terminal Gly-Lys-extended precursor, i.e., SP-G-K, displayed very similar chromatographic behavior as demonstrated for chemically authentic standards. These biochemical data were complemented by immunohistochemical analyses demonstrating a pattern of immunohistochemical staining for the presence of SP-G-LI as a defined subset of SP-LI-containing neural elements. Here, reaction product was localized to dendritic, axonal, and terminal neuronal elements in representative CNS regions of the rat, with relatively high levels of SP-G-LI found within anatomical areas containing a high density of sensory terminal structures. In an attempt to provide correlative functional anatomy, a group of rats was treated with colchicine, in order to differentially localize SP-LI- and SP-G-LI-containing somata after inhibition of axoplasmic transport. Most prominently, colchicine administration engendered immunohistochemical visualization of both SP-LI- and SP-G-LI-positive cells in mesencephalic and brainstem regions associated with stress, pain responses, and central control of autonomic function. Within this context, the coordinate expression of both SP-LI- and of SP-G-LI-positive somata in discrete brain areas is probably indicative of high ongoing rates of tachykinin synthesis coupled to utilization.
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PMID:Biochemical characterization and anatomical distribution of a major form of unamidated precursor of substance P in rat brain. 172 13


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