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)

A patient with mycosis fungoides illustrates the problem of pain management during wound care and suggests the utility of a novel treatment, gabapentin. Skin lesions, be they induced through necrosis of tumor, therapy (e.g., radiotherapy), or by pressure ulceration, are often the cause of continuous pain or acute wound dressing pain. Optimizing the analgesic treatment in those patients is thus of major importance. Anti-inflammatory drugs and opioids are the cornerstones in the treatment of cancer pain but are rarely sufficient to control wound pain. Different adjuvant techniques can be used, including topical analgesics, psychological distraction techniques, anxiolytics, and co-analgesics. There is growing evidence that anticonvulsants, and sodium channel blockers in particular, are effective not only in neuropathic but also in inflammatory pain. Gabapentin, a voltage sensitive sodium and calcium channel blocker, was used as a co-analgesic to supplement morphine in this case of cancer wound dressing pain.
J Pain Symptom Manage 2001 Jul
PMID:Gabapentin for pain control in cancer patients' wound dressing care. 1151 5

Myotonic disorders are characterised by slowed muscle relaxation and myotonic discharges in the electromyogram. "Pure" myotonic disorders affect only muscle and can be separated into ion channel disorders affecting either the chloride channel (myotonia congenita Thomsen or myotonia congenita Becker) or those affecting the sodium channel (paramyotonia, hyperkalemic periodic paralysis, and myotonia fluctuans). The genetic defects in these disorders are point mutations or deletions within the respective channel genes. A second group of myotonias consists of multisystem disorders with muscle weakness and atrophy plus extramuscular symptoms and signs including cardiac arrhythmias, cataracts, hypogonadism, and pain. Classic myotonic dystrophy (Steinert's disease or DM 1), and proximal myotonic myopathy (PROMM or Ricker's syndrome) are the major syndromes. PROMM is characterised by predominantly proximal muscle weakness and myalgias. Similarly to DM 1, anticipation also occurs in PROMM, but the disease course is usually milder. Steinert's disease belongs to the group of trinucleotide repeat-associated disorders. The DM 1 mutation is an unstable CTG trinucleotide repeat expansion on chromosome 19q13.3 which is diagnostic for the disease. A number of families with PROMM have been linked to a gene locus on chromosome 3q, but the mutation is still unknown. Therefore, direct molecular genetic testing for PROMM is not yet possible.
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PMID:[Myotonic dystrophy (DM/Curschmann-Steinert disease) and proximal myotonic myopathy (PROMM/Ricker syndrome). Myotonic muscle diseases with multisystemic manifestations]. 1151 2

Clinicians currently base decisions regarding the use of intrathecal drug therapy for chronic pain on reports from uncontrolled and retrospective studies that fail to rely on standardized outcome measures. In this article, we summarize what is known about currently administered intrathecal therapies, including opioids, gamma-aminobutyric acid agonists, alpha-2 adrenoreceptor agonists, local anesthetics (sodium channel antagonists), calcium channel antagonists, miscellaneous agents, and drug combination therapy. In addition, we offer a brief look at novel approaches that may revolutionize intrathecal drug delivery.
Curr Pain Headache Rep 2001 Dec
PMID:Spinal drug delivery. 1167 85

Our previous studies showed that the ectopic discharges in injured sensory neurons and mechanical allodynia that developed after spinal nerve ligation were significantly reduced by application of a low concentration of tetrodotoxin (TTX) to the corresponding dorsal root ganglion (DRG) of the ligated spinal nerve. Based on these data, we hypothesized that expression of TTX-sensitive sodium channels is up-regulated in the injured sensory neurons and that such up-regulation plays an important role in the generation of ectopic discharges and thus pain behaviors in spinal nerve ligated neuropathic rats. To test this hypothesis, the present study examined the changes in three subtypes of TTX-sensitive sodium channels in the DRG after spinal nerve ligation. The changes in the total amount of mRNA for alpha-subunits of sodium channel brain type I (type I), brain type II (type II) and brain type III (type III) were determined by RNase protection assays (RPA). The population of DRG neurons expressing type III sodium channel protein was examined by an immunohistochemical method with antibodies to type III sodium channels. In the normal DRG, the level of mRNA for the type I sodium channel is high while that for type II and type III is very low. After spinal nerve ligation, the expression of type III mRNA was significantly increased at 16-h postoperatively (PO), doubled by 3 days PO and then was maintained at this high level until the end of the experiment (7 days PO). By contrast, the amount of mRNA for type I and type II sodium channels started to decrease at 1 day PO and were reduced to 25-50% of the normal control levels by 7 days after nerve ligation. Neurons showing positive immunostaining for type III sodium channels were rare ( approximately 3.2% of total population) in the normal DRG but increased after nerve ligation to 21% and 15% of the total neuronal population by 1 day and 7 days PO, respectively. Type III immunoreactivity was found preferentially in medium to large sized neurons. Thus the majority of neurons with cell bodies having diameters > or =40 microm became type III-positive after nerve ligation. The data indicate that the increased expression of type III sodium channels in axotomized sensory neurons may be the critical factor for the TTX sensitivity of ectopic discharges in injured sensory neurons and thus the generation of ectopic discharges and neuropathic pain behaviors in spinal nerve ligated rats.
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PMID:The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation. 1168 87

Sodium channel blockers have been reported to be effective in relieving neuropathic pain. However, although intravenous lidocaine has proved to be effective, in some patients oral mexiletine fails to produce adequate pain relief. In this study, we investigated the analgesic effect of flecainide, a long-lasting antitachyarrhythmic drug, on postherpetic neuralgia. Twenty patients with postherpetic neuralgia received an intravenous infusion of flecainide and 15 (75%) of those who achieved pain relief subsequently received oral flecainide. The patients were assessed using a 100 mm visual analog scale 1 month after treatment. Significant improvement compared with the pretreatment reading was found. This study suggests that the action of flecainide in blocking the sodium channel is potent and long-lasting and that, like the intravenous formulation, the oral formulation has a stable analgesic effect on postherpetic neuralgia.
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PMID:Analgesic effects of flecainide on postherpetic neuralgia. 1170 71

Neuropathic pain is a debilitating consequence of nerve damage. Existing treatment is largely ineffective. Current models of neuropathic pain recognise the importance of ectopic activity in primary sensory neurones impinging on a sensitised central nervous system. Neurotrophic factors have been shown to be neuroprotective for damaged sensory neurones, providing a rationale for testing their effects in neuropathic pain states. Recent data have demonstrated potent analgesic effects of one factor (glial cell line-derived neurotrophic factor) in animal models of neuropathy, and implicated changes in sodium channel alpha-subunits in the generation of afferent ectopic activity. The new findings provide a rational basis for the use of neurotrophic factors as a novel therapeutic treatment for neuropathic pain states.
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PMID:Neurotrophic factors and neuropathic pain. 1171 38

1. Although sodium channel blockers are effective analgesics in neuropathic pain, their effectiveness in inflammatory pain has been little studied. Sodium channels are substantially up-regulated in inflamed tissue, which suggests they play a role in maintenance of chronic inflammatory pain. We have examined the effects of sodium channel blockers on mobility, joint hyperalgesia and inflammation induced by complete Freund's adjuvant injected in one ankle joint of adult rats. The clinically effective sodium channel blocker, mexiletine, was compared with crobenetine (BIII 890 CL), a new, highly use-dependent sodium channel blocker. 2. Rats were treated for 5 days, starting on the day of induction of arthritis and were tested daily for joint hyperalgesia, hind limb posture and mobility. At post-mortem, joint stiffness and oedema were assessed. Dose response curves were constructed for each test compound (3 - 30 mg kg day(-1)). Control groups were treated with vehicle or with the non-steroidal anti-inflammatory drug, meloxicam (4 mg kg day(-1) i.p.). 3. Both sodium channel blockers produced dose dependent and significant reversal of mechanical joint hyperalgesia and impaired mobility with an ID50 of 15.5+/-1.1 mg kg day(-1) for crobenetine and 18.1+/-1.2 mg kg day(-1) for mexiletine. Neither compound affected the responses of the contralateral non-inflamed joint, nor had any effect on swelling and stiffness of the inflamed joint. 4. We conclude that sodium channel blockers are analgesic and anti-hyperalgesic in this model of arthritis. These data suggest that up regulation of sodium channel expression in primary afferent neurones may play an important role in the pain and hyperalgesia induced by joint inflammation.
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PMID:Analgesic activity of a novel use-dependent sodium channel blocker, crobenetine, in mono-arthritic rats. 1173 51

Neuropathic pain is a debilitating chronic syndrome that often arises from injuries to peripheral nerves. Such pain has been hypothesized to be the result of an aberrant expression and function of sodium channels at the site of injury. Here, we show that intrathecal administration of specific antisense oligodeoxynucleotides (ODN) to the peripheral tetrodotoxin (TTX)-resistant sodium channel, NaV1.8, resulted in a time-dependent uptake of the ODN by dorsal root ganglion (DRG) neurons, a selective "knock-down" of the expression of NaV1.8, and a reduction in the slow-inactivating, TTX-resistant sodium current in the DRG cells. The ODN treatment also reversed neuropathic pain induced by spinal nerve injury, without affecting non-noxious sensation or response to acute pain. These data provide direct evidence linking NaV1.8 to neuropathic pain. As NaV1.8 expression is restricted to sensory neurons, this channel offers a highly specific and effective molecular target for the treatment of neuropathic pain.
Pain 2002 Jan
PMID:Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8. 1179 Apr 77

Carbamazepine (CBZ) has been extensively used in the treatment of epilepsy, as well as in the treatment of neuropathic pain and affective disorders. However, the mechanisms of action of this drug are not completely elucidated and are still a matter of debate. Since CBZ is not very effective in some epileptic patients and may cause several adverse effects, several antiepileptic drugs have been developed by structural variation of CBZ, such as oxcarbazepine (OXC), which is used in the treatment of epilepsy since 1990. (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz [b,f]azepine-5-carboxamide (BIA 2-093) and 10,11-dihydro-10-hydroxyimino-5H-dibenz[b,f] azepine-5-carboxamide (BIA 2-024), which were recently developed by BIAL, are new putative antiepileptic drugs, with some improved properties. In this review, we will focus on the mechanisms of action of CBZ and its derivatives, OXC, BIA 2-093 and BIA 2-024. The available data indicate that the anticonvulsant efficacy of these AEDs is mainly due to the inhibition of sodium channel activity.
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PMID:Mechanisms of action of carbamazepine and its derivatives, oxcarbazepine, BIA 2-093, and BIA 2-024. 1192 64

The tetrodotoxin-resistant sodium channel Na(V)1.8/SNS is expressed exclusively in sensory neurons and appears to have an important role in pain pathways. Unlike other sodium channels, Na(V)1.8 is poorly expressed in cell lines even in the presence of accessory beta-subunits. Here we identify annexin II light chain (p11) as a regulatory factor that facilitates the expression of Na(V)1.8. p11 binds directly to the amino terminus of Na(V)1.8 and promotes the translocation of Na(V)1.8 to the plasma membrane, producing functional channels. The endogenous Na(V)1.8 current in sensory neurons is inhibited by antisense downregulation of p11 expression. Because direct association with p11 is required for functional expression of Na(V)1.8, disrupting this interaction may be a useful new approach to downregulating Na(V)1.8 and effecting analgesia.
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PMID:Annexin II light chain regulates sensory neuron-specific sodium channel expression. 1205 Jun 67


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