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)

References were selected from a MEDLINE search from 1966-1993 for literature evaluating the drug therapy of diabetic peripheral neuropathy (DPN). The search was limited to studies evaluating symptomatic treatment, and methods were developed to include only well-designed clinical trials. Many recommendations for the symptomatic treatment of DPN appear in the medical literature, but are frequently based on case reports, information extrapolated from other neuropathic pain syndrome models, or treatment protocols lacking scientific methods. These recommendations include antidepressants, sodium channel antagonists, topical capsaicin, and miscellaneous agents. Anti-depressants are considered to be the first choice in these patients. Factors to consider in establishing a regimen are interpretation of studies, adverse drug effects, drug-drug and drug-disease interactions, convenience of administration, and cost of therapy. Potentially effective alternatives were determined from the reviewed trials.
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PMID:Review of the symptomatic treatment of diabetic neuropathy. 788 72

The axolemmal distribution of voltage-gated sodium channels largely determines the regions of axonal electrical excitability. Using a well-characterized anti-sodium channel antibody, we examined peripheral nerve fibers focally injured by exposure to the neurotoxic agent, potassium tellurite (K2TeO3). Immunocytochemical and radioimmunoassay data showed a focal accumulation of sodium channels within the tips of injured axons. The major increase in sodium channel concentration occurred between 7 and 11 days after toxin exposure; however, immunocytochemically, excess sodium channels persisted in several axonal endings for a much longer time. The accumulation of sodium channels at injured axonal tips may be responsible, in part, for ectopic axonal excitability and the resulting abnormal sensory phenomena (especially pain and paresthesias) which frequently complicate peripheral nerve injury in humans.
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PMID:Sodium channels accumulate at the tips of injured axons. 819 1

We investigated calcium ion effects on pain thresholds by iontophoresis in healthy adult volunteers. The pain thresholds were measured by the pain thermometer to evaluate the effect of iontophoresis. At first, one of calcium channel blockers (nicardipine, verapamil or diltiazem) was administered by iontophoresis with 1.0 mA for 10 minutes. Then, next to calcium channel blockers, calcium chloride or saline was locally administered after the elevation of pain threshold had been recognized and the pain threshold had been measured again. Calcium ion decreased the elevation of pain threshold significantly, but saline had no effect. These results suggest that not only sodium channel but also calcium channel influences pain mechanism during iontophoresis.
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PMID:[Reversal by the calcium ion of the pain threshold elevated by calcium channel blockers]. 851 46

Painful neuromas from 16 patients were examined using site-specific antisodium channel antibodies employed in immunocytochemical and radioimmunoassay methods. Normal sural nerves from six of these patients served as controls. Immunocytochemistry showed abnormal segmental accumulation of sodium channels within many axons in the neuromas. Dens immunolocalization was especially apparent within the axonal tips. Radioimmunoassay confirmed a significantly greater density of sodium channels in the neuromas as compared with the sural nerves. Thus, sodium channel accumulate abnormally within the axons of neuromas in humans. This alteration of the sodium channels may underlie the generation of axonal hyperexcitability and the resulting abnormal sensory phenomena (pain and paresthesias), which frequently occur after peripheral nerve injury.
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PMID:Sodium channel accumulation in humans with painful neuromas. 871 95

The action of lignocaine on nociceptive transmission in the spinal cord has been studied in vitro using ventral root potential (VRP) recordings from 10-12-day-old rat hemisected spinal cord preparations. Single-shock stimulation of a dorsal root at intensities sufficient to activate high-threshold C-primary afferent fibres elicited VRPs lasting for 15-20 sec in the corresponding ventral root. The VRP consisted of 3 distinct parts: the early, slow and prolonged components, as previously described (Thompson et al. 1992), where the early represents A beta fibre-evoked mono- and polysynaptic responses lasting for tens of milliseconds, the slow is a largely N-methyl-D-aspartic acid (NMDA) receptor-mediated small-calibre afferent-generated component, lasting for about 1.5 sec, and the prolonged is a neurokinin receptor-mediated long-lasting component generated by high-threshold fibres. Lignocaine superfusion (40-60 microM) significantly and reversibly reduced the slow and prolonged components of the C fibre-evoked VRP in a dose-dependent manner without any effect on the early or A beta fibre-mediated component of the VRP. The amplitude of the cumulative VRP generated by repetitive inputs (1 and 10 Hz) was also significantly reduced as was the depolarization produced by bath application of NMDA (100 microM) or substance P (SP, 1 microM) in the presence or absence of tetrodotoxin (TTX) (300 nM). At this dose range lignocaine had no effect on the compound action potential (CAP) elicited by stimulating the sciatic nerve and recorded on the dorsal root. The CAP was only significantly reduced with a 300 microM dose of lignocaine. Application of the opiate, glycine, GABAA and GABAB receptor antagonists, naloxone (1 microM), strychnine (100 microM), bicuculline (100 microM) and phaclofen (100 microM) did not alter the depressant effects of lignocaine on the VRP. Low concentrations of lignocaine have a selective action on nociceptive transmission in the spinal cord which is different and more potent than its local anaesthetic conduction blockade in the periphery. This includes a reduction of direct or synaptically driven NMDA- and NK receptor-mediated post-synaptic depolarizations indicating that this class of sodium channel blockers may be potentially useful as analgesic agents, possibly acting on TTX-resistant sodium ion channels.
Pain 1996 Jan
PMID:Lignocaine selectively reduces C fibre-evoked neuronal activity in rat spinal cord in vitro by decreasing N-methyl-D-aspartate and neurokinin receptor-mediated post-synaptic depolarizations; implications for the development of novel centrally acting analgesics. 886 47

A selective blockade of the relay of messages by C-fibres into the spinal cord is a logical approach to the reduction of nociceptive transmission. Here we compared the effect of two distinctly different sodium channel blockers, the local anaesthetic bupivacaine and the novel anti-epileptic lamotrigine, on the responses of dorsal horn neurones following noxious and innocuous stimulation. Dorsal horn neuronal responses following acute repetitive C-fibre electrical stimulation (three times the C-fibre threshold at 0.5 Hz) were recorded in intact halothane anaesthetised rats. Wind up, an enhanced C-fibre evoked response of dorsal horn neurones, and an associated post discharge were observed following repetitive stimulation. The effects of spinally administered bupivacaine and lamotrigine on the dorsal horn neuronal responses were investigated. Spinal bupivacaine (25-1000 microg/50 microl) dose dependently reduced the C-fibre evoked responses (r2 = 0.5, P < 0.0003), wind up (r2 = 0.4, P < 0.002) and the post discharge (r2 = 0.34, P < 0.005) of these neurones. The effects of bupivacaine were long lasting, up to 120 min post-administration. The Abeta-fibre evoked responses were not dose-dependently reduced by bupivacaine. Spinal lamotrigine (50-1000 microg/50 microl) did not significantly reduce the C- or Abeta-fibre evoked responses. In contrast there was a tendency for wind up and post discharge to be facilitated by lamotrigine. Although both bupivacaine and lamotrigine are sodium channel blockers, the effects of the two drugs on the C-fibre and Abeta-fibre evoked responses were completely different. Bupivacaine reduced C-fibre evoked responses whereas lamotrigine had a tendency to facilitate responses. The profile of sodium channel blockers would appear highly diverse and the status of lamotrigine as a potential analgesic remains unclear.
Pain 1997 Jul
PMID:Distinct electrophysiological effects of two spinally administered membrane stabilising drugs, bupivacaine and lamotrigine. 923 72

Mutations in the skeletal muscle voltage-gated sodium channel alpha-subunit gene (SCN4A) have been associated with a spectrum of inherited nondystrophic myotonias and periodic paralyses. Most disease-associated SCN4A alleles occur in portions of the gene that encode the third and fourth repeat domains with the conspicuous absence of mutations in domain 1. Here we describe a family segregating an unusual autosomal dominant congenital myotonia associated with debilitating pain especially severe in the intercostal muscles. A novel SCN4A mutation causing the replacement of Val445 in the sixth transmembrane segment of domain 1 with methionine was discovered in all affected individuals and is the likely genetic basis for the syndrome. Myotonia was resistant to treatment; however, the most severely affected family member responded dramatically to the sodium channel blocking agent flecainide.
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PMID:A novel muscle sodium channel mutation causes painful congenital myotonia. 939 83

The delayed onset of painful paresthesias following trauma to a peripheral nerve is a well recognized but poorly understood phenomenon. This report describes an illustrative case of painful paresthesias in the territory of the ilioinguinal nerve, 3 to 6 weeks after an otherwise routine herniorraphy, which subsequently responded dramatically to carbamazepine. The case is considered in light of recent studies which have determined molecular changes which occur in dorsal root ganglion (DRG) neurons following axotomy and neuroma formation. Voltage-dependent sodium (Na+) channels in DRG neurons undergo a change following axotomy, in which there is significant up- and down-regulation of different subpopulations of Na channels over a time frame measured in days to weeks. Such changes may render the DRG neurons hyperexcitable, thus contributing to a neuropathic pain syndrome, yet susceptible to treatment with a sodium channel blocker such as carbamazepine.
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PMID:Successful treatment of painful traumatic mononeuropathy with carbamazepine: insights into a possible molecular pain mechanism. 939 32

A 64-year-old man developed a severe generalized pruritic morbilliform skin eruption, fever, eosinophilia, atypical lymphocytosis, and liver dysfunction 30 days after ingestion of mexiletine, a sodium channel blocker, prescribed to treat postherpetic neuralgia. Following intravenous dexamethasone, body temperature normalized the next day. However, the skin eruption did not disappear completely for 4 weeks. The patch test was positive for mexiletine. Clinical features and the result of patch test indicated that the patient developed hypersensitivity syndrome, a severe adverse cutaneous drug reaction, caused by mexiletine. We propose that mexiletine be added to the list of drugs that can cause severe adverse cutaneous drug reactions and that patients receiving mexiletine be warned to stop taking the drug immediately if a skin eruption occurs.
Pain 1997 Oct
PMID:Mexiletine-induced severe skin eruption, fever, eosinophilia, atypical lymphocytosis, and liver dysfunction. 941 61

Voltage-gated tetrodotoxin (TTX)-resistant sodium channels present in primary sensory neurons may be responsible for the excitability of nociceptors, and may underlie pain and tenderness associated with tissue injury and inflammation. Here, we report the cloning of a putative sodium channel (NaNG) from dog nodose ganglia. The sequence of the full-length cDNA predicts an open reading frame of 5886 nucleotides encoding a protein of 1962 amino acids. The predicted protein shows 82.3% identity with the recently discovered TTX-resistant sodium channel (SNS/PN3). In the TTX-binding site, a serine appears as in TTX-resistant SNS/PN3, instead of Cys (as in TTX-insensitive cardiac channels) and Tyr/Phe (as in TTX-sensitive sodium channels). Coupled transcription and translation of full-length cDNA produced a 220-kDa protein; based on Northern blot and RT-PCR analysis, its expression is restricted to nodose ganglia, and not present in cortex, hippocampus, cerebellum, liver, heart or skeletal muscle. We propose that NaNG might be a new member of the TTX-resistant sodium channel family expressed in sensory neurons.
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PMID:Molecular cloning of a putative tetrodotoxin-resistant sodium channel from dog nodose ganglion neurons. 942 39


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