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)

Pigmentation may result from melanocyte proliferation, melanogenesis, migration or increases in dendricity. Recently, it has been reported that secreted phospholipase A(2)(sPLA(2)) known as a component of bee venom (BV), stimulates melanocyte dendricity and pigmentation. BV has been used clinically to control rheumatoid arthritis and to ameliorate pain via its anti-inflammatory and antinociceptive properties. Moreover, after treatment with BV, pigmentation around the injection sites was occasionally observed and the pigmentation lasted a few months. However, no study has been done about the effect of BV on melanocytes. Thus, in the present study, we examined the effect of BV on the proliferation, melanogenesis, dendricity and migration in normal human melanocytes and its signal transduction. BV increased the number of melanocytes dose and time dependently through PKA, ERK, and PI3K/Akt activation. The level of cAMP was also increased by BV treatment. Moreover, BV induced melanogenesis through increased tyrosinase expression. Furthermore, BV induced melanocyte dendricity and migration through PLA(2) activation. Overall, in this study, we demonstrated that BV may have an effect on the melanocyte proliferation, melanogenesis, dendricity and migration through complex signaling pathways in vitro, responsible for the pigmentation. Thus, our study suggests a possibility that BV may be developed as a therapeutic drug for inducing repigmentation in vitiligo skin.
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PMID:Bee venom stimulates human melanocyte proliferation, melanogenesis, dendricity and migration. 1805 36

Activation of the spinal phospholipase A(2) (PLA(2)) -cyclooxygenase (COX) -prostaglandin signaling pathway is widely implicated in nociceptive processing. Although the role of spinal COX isoforms in pain signal transmission has been extensively characterized, our knowledge of PLA(2) enzymes in this cascade is limited. Among all PLA(2) groups, cytosolic calcium-dependent PLA(2) group IVA (cPLA(2)IVA) appears to be the predominant PLA(2) enzyme in the spinal cord. In the present study we sought to (i) characterize anatomical and cellular distribution and localization of cPLA(2)IVA in dorsal horn of rat spinal cord, (ii) verify efficacy and selectivity of intrathecal (IT) delivery of an antisense oligonucleotide (AS) targeting rat cPLA(2)IVA mRNA on spinal expression of this enzyme, and (iii) examine the effect of down-regulation of spinal cPLA(2)IVA on peripheral tissue injury-induced pain behavior. Here we demonstrate that cPLA(2)IVA is constitutively expressed in rat spinal cord, predominantly in dorsal horn neurons and oligodendrocytes but not in astrocytes or microglia. Intrathecal injection of AS significantly down-regulated both protein and gene expression of cPLA(2)IVA in rat spinal cord, while control missense oligonucleotide (MS) had no effect. Immunocytochemistry confirmed that the reduction occurred in neurons and oligodendrocytes. cPLA(2)IVA AS did not alter expression of several other PLA(2) isoforms, such as secretory PLA(2) (groups IIA and V) and calcium-independent PLA(2) (group VI), indicating that the AS was specific for cPLA(2)IVA. This selective knockdown of spinal cPLA(2)IVA did not change acute nociception (i.e. paw withdrawal thresholds to acute thermal stimuli and intradermal formalin-induced first phase flinching), however, it significantly attenuated formalin-induced hyperalgesia (i.e. second phase flinching behavior), which reflects spinal sensitization. Thus the present findings suggest that cPLA(2)IVA may specifically participate in spinal nociceptive processing.
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PMID:Inhibition of spinal cytosolic phospholipase A(2) expression by an antisense oligonucleotide attenuates tissue injury-induced hyperalgesia. 1851 Dec 7

Centipedes have a venom gland connected to a pair of forceps, which are used to arrest preys. Human victims bitten by centipedes usually manifest burning pain, paresthesia and edema, which may develop into superficial necrosis. The aim of this work was to characterize and compare toxic activities found in venoms of three species of Brazilian centipedes-Otostigmus pradoi, Cryptops iheringi and Scolopendra viridicornis. By SDS-PAGE (4-20%), important differences were noticed among venoms (between 7 and 205kDa). Few bands showed feeble caseinolytic, fibrinogenolytic and gelatinolytic activities by zymography, but strong hyaluronidase activity was observed in S. viridicornis and O. pradoi venoms. In addition, such activities could be inhibited by o-phenanthroline, indicating that these enzymes are metalloproteinases. All venoms induced nociception, edema and myotoxicity in mice, but only S. viridicornis induced mild hemorrhagic activity. No coagulant activity was detected in centipede venoms. Low phospholipase A(2) activity was observed exclusively in S. viridicornis and O. pradoi venoms, but these venoms had intense direct hemolytic activity on human erythrocytes. Cross-reactivity among venoms was observed using species-specific sera raised in rabbits. Differences were noticed among centipede venoms, but S. viridicornis is indeed the most toxic venom and thereby it could induce a more severe envenomation.
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PMID:Toxic activities of Brazilian centipede venoms. 1858 47

Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) is a simple phospholipid but displays an intriguing cell biology that is mediated via interactions with G protein-coupled seven transmembrane receptors (GPCRs). So far, five GPCRs, designated LPA1-5, and, more recently, two additional GPCRs, GPR87 and P2Y5, have been identified as receptors for LPA. These LPA receptors can be classified into two families, the EDG and P2Y families, depending on their primary structures. Recent studies on gene targeting mice and family diseases of these receptors revealed that LPA is involved in both pathological and physiological states including brain development (LPA1), neuropathy pain (LPA1), lung fibrosis (LPA1), renal fibrosis (LPA1) protection against radiation-induced intestinal injury (LPA2), implantation (LPA3) and hair growth (P2Y5). LPA is produced both in cells and biological fluids, where multiple synthetic reactions occur. There are at least two pathways for LPA production. In serum or plasma, LPA is predominantly produced by a plasma enzyme called autotaxin (ATX). ATX is a multifunctional ectoenzyme and is involved in many patho-physiological conditions such as cancer, neuropathy pain, lymphocyte tracking in lymph nodes, obesity, diabetes and embryonic blood vessel formation. LPA is also produced from phosphatidic acid (PA) by its deacylation catalyzed by phospholipase A (PLA)-type enzymes. However, the physiological roles of this pathway as well as the enzymes involved remained to be solved. A number of phospholipase A1 and A2 isozymes could be involved in this pathway. One PA-selective PLA1 called mPA-PLA1alpha/LIPH is specifically expressed in hair follicles, where it has a critical role in hair growth by producing LPA through a novel LPA receptor called P2Y5.
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PMID:Two pathways for lysophosphatidic acid production. 1862 Nov 44

We previously reported that nerve injury-induced neuropathic pain and its underlying mechanisms are initiated by lysophosphatidic acid. In the present study, by measuring cell-rounding in a biological assay using lysophosphatidic acid 1 receptor-expressing B103 cells, we evaluated the molecular mechanism underlying lysophosphatidic acid biosynthesis following intense stimulation of primary afferents. Lysophosphatidic acid production was induced by treatment of spinal cord slices with capsaicin (10 microM), an intense stimulator of primary afferents, in the presence of recombinant autotaxin, but not in its absence. Lysophosphatidic acid was also induced by combination treatment of slices with high doses (10 and 30 microM) of substance P and NMDA, but not by other combinations of substance P, NMDA, calcitonin gene-related peptide and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (30 microM each) in the presence of recombinant autotaxin. We also found that following neurokinin 1 and NMDA receptor activation, activation of both cytosolic phospholipase A(2) and calcium-independent intracellular phospholipase A(2) signalling pathways through protein kinase C and mitogen-activated protein/extracellular signal-regulated kinase activation and intracellular calcium elevation were required for lysophosphatidic acid production. These findings suggest that simultaneous intense stimulation of neurokinin 1 and NMDA receptors in the spinal dorsal horn triggers lysophosphatidic acid production from lysophosphatidylcholine through extracellular autotaxin.
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PMID:Simultaneous stimulation of spinal NK1 and NMDA receptors produces LPC which undergoes ATX-mediated conversion to LPA, an initiator of neuropathic pain. 1901 89

Milk whey proteins contain major components of alpha-lactalbumin (alphaLA) and beta-lactoglobulin (betaLG), and a minor component of lactoferrin (LF). It has been reported that LF reduces nociception and inflammation in various animal models. However, the efficacy of alphaLA and betaLG has not been clarified. This study aimed to assess the efficacy of alphaLA and betaLG in various animal models such as acetic acid-induced writhing, carrageenan-induced paw inflammation, and adjuvant induced-arthritis. Orally administered alphaLA showed (i) inhibition of writhing induced by acetic acid in mice; (ii) suppression of nociception and inflammation in rat footpads caused by carrageenan in rat; and (iii) therapeutic effects on the development of adjuvant-induced pain and inflammation in rat. In contrast, betaLG had no effects in these animal models. To clarify the anti-nociceptive and anti-inflammatory mechanisms of alphaLA, we examined the levels of interleukin (IL)-6 and prostaglandin (PG)E(2) in carrageenan-injected paw exudates. The administration of alphaLA 1 h before carrageenan injection inhibited the increased formation of IL-6 and PGE(2) in paw exudates. Next, we demonstrated in vitro enzyme-inhibition assay; cyclooxygenase (COX), phospholipase A(2), and 5-lipoxygenase. alphaLA inhibited COX and phospholipase A(2) activities. alphaLA inhibited COX and phospholipase A(2) activities. Moreover, alphaLA showed selectivity on COX-2 as compared with COX-1. However, 5-lipoxygenase activity was not affected by alphaLA. These results suggest that alphaLA is a safe and useful natural drug for patients that require anti-inflammatory drugs, as alphaLA is contained in dairy food and is frequently ingested as daily food.
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PMID:Novel functions of bovine milk-derived alpha-lactalbumin: anti-nociceptive and anti-inflammatory activity caused by inhibiting cyclooxygenase-2 and phospholipase A2. 1925 79

Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.
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PMID:Lipoxygenase inhibitors suppressed carrageenan-induced Fos-expression and inflammatory pain responses in the rat. 1939 Aug 22

To explore the main clinical manifestation (lower back pain and ischialgia) of LDH with immunologic method and study the relationship and clinical significance of the cardinal symptom (pain) and immune comple (IC), macrophage (MP),interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), prostaglandin E2 (PGE2), phosphatidase A2 (PLA2), nitrogen monoxidum (NO) expressing, finding a new way in order to prevention and cure of LDH. We will review immunologic theory of LDH pain.
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PMID:[Immunologic theory investigation and discussion of pain caused by lumbar intervertebral disc herniation (LDH)]. 1940 76

This study evaluated the anti-asthmatic activities of four diterpene acids isolated from Aralia cordata root that are proposed to be the active ingredients in its traditional use as a treatment for inflammation, overheating, pain and spasm in Korea. The diterpene acids were identified as kaurenoic acid, 7-oxo-sandaracopimaric acid, 17-hydroxy-ent-kaur-15-en-19-oic acid, and hederagenin, by comparing their phytochemical and spectroscopic data with previous reports. The effects of diterpene acids on asthma were evaluated by determining the specific airway resistance (sRaw) during the immediate asthmatic response (IAR) and the late-phase asthmatic response (LAR) in guinea pigs with IgE-mediated asthma. Recruitment of leukocytes and the presence of chemical mediators in bronchoalveolar lavage fluid (BALF) were determined, and histopathological surveys performed. The four diterpene acids dosed at 25 approximately 100 mg/kg had dose-dependently anti-asthmatic effects: 7-oxo-sandaracopimaric acid > 17-hydroxy-ent-kaur-15-en-19-oic acid > kaurenoic acid > hederagenin. 7-oxo-sandaracopimaric acid (25 mg/kg) significantly (p < 0.05) inhibited sRaw by 59.5% in IAR and LAR, and also dose-dependently inhibited recruitment of eosinophils and neutrophils into lung and release of chemical mediators, histamine, and the activity of phospholipase A(2) and eosinophil peroxidase in BALF. 7-Oxo-sandaracopimaric acid had the highest activity among the diterpene acids. But its effect was lower than cromolyn sodium, salbutamol, or dexamethasone in both the IAR and the LAR. These results suggested that C(7)-oxo radical of 7-oxo-sandaracopimaric acid was more active than the C(7)-hydroxy and hydrogen of the other compounds, and showed diterpene acids have anti-asthmatic effects, supporting the traditional application of this herb in treating IgE-mediated asthma.
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PMID:Inhibitory effects of diterpene acids from root of Aralia cordata on IgE-mediated asthma in guinea pigs. 2006 54

Phospholipases A(2) (PLA(2)) are enzymes which cleave the sn-2 ester bond in membrane phospholipids to release free fatty acids and lysophospholipids. The present study aimed to elucidate the expression profile of multiple secretory phospholipase A(2) (sPLA(2)) isoforms in the normal rat CNS with focus on sPLA(2)-IIA in the brainstem and spinal cord. Quantitative RT-PCR analysis showed that sPLA(2)-IB expression was low throughout the CNS, sPLA(2)-IIA expression was high in the brainstem and spinal cord, sPLA(2)-IIC expression was high in the cerebral neocortex, hippocampus and thalamus/hypothalamus, sPLA(2)-V expression was high in the olfactory bulb and cerebellum, and sPLA(2)-X was expressed at very low levels in the normal CNS. Of the isoforms, sPLA(2)-IIA mRNA expression was highest in the brainstem and spinal cord suggesting that this could be the most relevant isoform in the ascending pain pathway. Western blot analysis showed high level of sPLA(2)-IIA expression in the brainstem and cervical, thoracic and lumbar spinal segments but low level of expression in other parts of the brain. sPLA(2)-IIA was localized by immunohistochemistry to the spinal trigeminal and facial motor nuclei and dorsal- and ventral-horns of the spinal cord. The enzyme was found on the endoplasmic reticulum of neuronal cell bodies and small diameter dendrites or dendritic spines at electron microscopy. The expression of sPLA(2)-IIA in the dorsal horn and spinal trigeminal nucleus is consistent with previous results which showed an important role of CNS sPLA(2) in nociceptive transmission.
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PMID:Expression profile of multiple secretory phospholipase A(2) isoforms in the rat CNS: enriched expression of sPLA(2)-IIA in brainstem and spinal cord. 2015 19


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