Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of plant species used in traditional medicine for the relief of pain have been selected from the medicinal and scientific literature of China, South America, Asia and West Africa. Extracts were prepared and tested in three in vitro receptor radioligand binding assays to determine whether there was an indication of biological activity, in particular their selectivity to a single receptor implicated in the mediation of pain. The three neuropeptide receptors chosen were Bradykinin (BK II), expressed in Chinese hamster ovary cells (CHO), neurokinin 1 (NK 1) expressed in astrocytoma cells, and calcitonin gene related peptide (CGRP) which were all implicated in the mediation of acute pain in the mammaliancentral nervous system. The plant species chosen to investigate were Ageratum conyzoides, Barringtonia edulis, Croton tiglium, Ipomea pes-caprae, Panax ginseng, Physostigma venenosum, Sinomenium acutum, Solidago virgaurea, Symplocos leptophylla and Typhonium giganteum. The results showed that there was a strong indication of biological activity for some of the plants which are used ethnomedicinally to treat pain, in the three in vitro receptor binding assays used, and particular plant extracts exhibited selective action to a single receptor.
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PMID:Ethnomedicinally selected plants as sources of potential analgesic compounds: indication of in vitro biological activity in receptor binding assays. 1064 Oct 43

Bradykinin produced at sites of tissue injury and inflammation elicits acute pain and alters the sensitivity of nociceptive neurons to subsequent stimuli. We tested the hypothesis that bradykinin could elicit long-lasting changes in nociceptor function by activating members of the nuclear factor of activated T-cells (NFAT) family of transcription factors. Bradykinin activation of B2 receptors evoked concentration-dependent (EC50 = 6.0 +/- 0.3 nM) increases in intracellular Ca2+ concentration ([Ca2+]i) in a proportion of dorsal root ganglion neurons in primary culture. These [Ca2+] increases were sensitive to inhibition of phospholipase C (PLC) and depletion of Ca2+ stores. In neurons expressing a green fluorescent protein (GFP)-NFAT4 fusion protein, a 2-min exposure to bradykinin induced the translocation of GFP-NFAT4 from the cytoplasm to the nucleus. Translocation was partially inhibited by the removal of extracellular Ca2+ and was blocked by inhibition of calcineurin. Furthermore, bradykinin triggered a concentration-dependent increase in NFAT-mediated transcription of a luciferase gene reporter (EC50 = 24.2 +/- 0.1 nM). This depended on the B2 receptor, PLC activation, and inositol triphosphate-mediated Ca2+ release. Transcription was not inhibited by capsazepine. Finally, as indicated by quantitative reverse transcription-polymerase chain reaction, bradykinin elicited an increase in cyclooxygenase mRNA. This increase was sensitive to calcineurin and B2 receptor inhibition. These findings suggest a mechanism by which short-lived bradykinin-mediated stimuli can enact lasting changes in nociceptor function and sensitivity.
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PMID:Bradykinin-induced nuclear factor of activated T-cells-dependent transcription in rat dorsal root ganglion neurons. 1748 65

Altered function of Na+ channels is responsible for increased hyperexcitability of primary afferent neurons that may underlie pathological pain states. Recent evidence suggests that the Nav1.9 subunit is implicated in inflammatory but not acute pain. However, the contribution of Nav1.9 channels to the cellular events underlying nociceptor hyperexcitability is still unknown, and there remains much uncertainty as to the biophysical properties of Nav1.9 current and its modulation by inflammatory mediators. Here, we use gene targeting strategy and computer modeling to identify Nav1.9 channel current signature and its impact on nociceptors' firing patterns. Recordings using internal fluoride in small DRG neurons from wild-type and Nav1.9-null mutant mice demonstrated that Nav1.9 subunits carry the TTX-resistant "persistent" Na+ current called NaN. Nav1.9(-/-) nociceptors showed no significant change in the properties of the slowly inactivating TTX-resistant SNS/Nav1.8 current. The loss in Nav1.9-mediated Na+ currents was associated with the inability of small DRG neurons to generate a large variety of electrophysiological behaviors, including subthreshold regenerative depolarizations, plateau potentials, active hyperpolarizing responses, oscillatory bursting discharges, and bistable membrane behaviors. We further investigated, using CsCl- and KCl-based pipette solutions, whether G-protein signaling pathways and inflammatory mediators upregulate the NaN/Nav1.9 current. Bradykinin, ATP, histamine, prostaglandin-E2, and norepinephrine, applied separately at maximal concentrations, all failed to modulate the Nav1.9 current. However, when applied conjointly as a soup of inflammatory mediators they rapidly potentiated Nav1.9 channel activity, generating subthreshold amplification and increased excitability. We conclude that Nav1.9 channel, the molecular correlate of the NaN current, is potentiated by the concerted action of inflammatory mediators that may contribute to nociceptors' hyperexcitability during peripheral inflammation.
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PMID:Inflammatory mediators increase Nav1.9 current and excitability in nociceptors through a coincident detection mechanism. 1827 Jan 72

Bradykinin is the most potent endogenous inducer of acute pain. However, the way in which it excites nociceptive sensory nerve endings is still unclear. In an article recently published in the JCI, Liu et al. suggest a new mechanism via which bradykinin induces acute spontaneous pain. The authors report that the stimulation of B2 bradykinin receptors by bradykinin triggers the release of intracellular calcium ions from nociceptive sensory neurons of rat dorsal root ganglia. This depolarizes the sensory nerve endings by simultaneously closing M-type potassium channels and opening TMEM16A chloride channels, resulting in the production of nociceptive signals. Here, we discuss the relationship between this effect and a previously described mechanism for pain sensitization and evaluate its potential significance for therapeutic pain control. A separate study by Patwardhan et al. in this issue of the JCI identifies oxidized linoleic acid metabolites as novel mediators of thermally induced pain.
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PMID:Some new insights into the molecular mechanisms of pain perception. 2042 17