Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain is a very difficult problem with which the neurosurgeon frequently must deal. The neurosurgical methods to be considered are: (1) modulative, by using neurostimulation or implanted drug delivery systems, and (2) ablative, by making selective therapeutic lesions in well-defined and identified targets proven to sustain pain mechanisms (especially DREZotomy).
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PMID:Neurosurgical management of neuropathic pain. 1174 Jan 73

Neuropathic pain may be defined as pain related to abnormal somatosensory processing in either the peripheral or central nervous system. This pathophysiologic label is typically applied when the painful symptom is associated with an overt injury to neural structures, is part of a recognized syndrome, or has a dysesthetic quality (usually burning, shooting, or electrical). Most neural injury does not lead to clinically important neuropathic pain, but sometimes even a small degree of tissue injury can precipitate severe pain. In the cancer population, neuropathic pain is often related to compression, direct neoplastic invasion of the peripheral nerves or spinal cord, or to a neuropathy caused by chemotherapy. To manage neuropathic pain in this population, nonopioid adjuvant drugs that are neuroactive or neuromodulatory are often needed to complement opioid therapy. The primary adjuvant analgesics are anticonvulsant and antidepressant medications, but a wide variety of other drugs are also used. To optimize analgesic therapy in patients with neuropathic pain, both opioid and adjuvant analgesics must be used effectively.
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PMID:Neuropathic cancer pain: the role of adjuvant analgesics. 1175 72

Neuropathic pain is frequently associated with hyperexcitability of primary afferents, characterized by spontaneous impulses and repetitive firing. Electrophysiology and molecular biology reveal changes in dorsal root ganglion Na+ channels under conditions of neuropathic pain, but the manner by which these changes alter the physiology of sensory afferents remains unknown. Equally mysterious is the mechanism by which i.v. local anaesthetic-like Na+ channel blockers suppress neuropathic pain behaviour at concentrations well below those reported for channel inhibition. We have compared the anti-allodynic actions of i.v. lidocaine (L) and stereoisomers of mexiletine (R-M, S-M), in rats after spinal nerve ligation, with their ability: (1) to inhibit fast, tetrodotoxin-sensitive neuronal Na+ currents, elicited by brief (1 ms) pulses, at 10 Hz, from 'resting' potentials (-80, -60 mV) and (2) to suppress the seconds long plateau and the repetitive firing produced in axons by slowing of Na+ channel inactivation (e.g. using scorpion alpha-toxins). Both L and R-M at 5-10 microM relieved allodynia; S-M was ineffective. Na+ currents also were inhibited by M, with affinities that were increased by both repetitive 'firing' (K(R,S) = 5 microM) and depolarization of the 'resting' membrane (K(R) = 15 microM; K(S) = 30 microM). Stereopotency ratios depended on the manner in which different states of the channel were inducted. Both L and M shortened the action potential's 'plateau' in alpha-toxin treated axons, without reducing the spike, and suppressed repetitive firing with IC(50)s = 5 microM, and no stereoselectivity. These findings together demonstrate that Na+ channel blockers, at 'therapeutic' concentrations, can inhibit neuronal hyperexcitability.
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PMID:Therapeutic concentrations of local anaesthetics unveil the potential role of sodium channels in neuropathic pain. 1177 46

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

Increased glutamate availability in the spinal cord and primary afferent nerves plays an important role in acute and chronic pain. Afferent ectopic discharges from the site of nerve injury constitute a source of abnormal sensory input to the spinal dorsal horn. The ectopic afferent activity is largely responsible for the development of hypersensitivity of dorsal horn neurons and neuropathic pain. Inhibition of glutamate carboxypeptidase II (GCP II) reduces glutamate release generated from N-acetyl-aspartyl-glutamate in nerve tissues and may have an analgesic effect on neuropathic pain. In the present study, we determined the effect of a GCP II inhibitor, 2-(phosphono-methyl)-pentanedioic acid (2-PMPA), on allodynia and ectopic afferent discharges in an animal model of neuropathic pain. Neuropathic pain was induced by partial ligation of the left sciatic nerve in rats. Tactile allodynia was assessed using von Frey filaments applied to the plantar surface of the injured hindpaw. Single-unit activity of ectopic discharges was recorded from the sciatic nerve proximal to the site of ligation. Intravenous injection of 50 to 100 mg/kg 2-PMPA significantly reduced allodynia in a dose-dependent manner. Furthermore, 2-PMPA dose-dependently attenuated the ectopic discharge activity of injured sciatic afferent nerves. At a dose of 100 mg/kg, 2-PMPA significantly inhibited the ectopic activity from 14.7 +/- 2.1 to 4.4 +/- 0.5 impulses/s without altering the conduction velocity of afferent nerves. Therefore, these data suggest that the antiallodynic effect of 2-PMPA may be mediated, at least in part, by inhibition of ectopic afferent discharges at the site of nerve injury.
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PMID:Effect of 2-(phosphono-methyl)-pentanedioic acid on allodynia and afferent ectopic discharges in a rat model of neuropathic pain. 1180 30

Neuropathic pain (characterized by hyperalgesia and allodynia to mechanical and thermal stimuli) causes cellular changes in spinal dorsal horn neurons, some of which parallel those in synaptic plasticity associated with learning. Ubiquitin C-terminal hydrolase (UCH) appears to play a key role in long-term facilitation in Aplysia. The cooperation of UCH with the proteolytic enzyme complex known as the proteasome is required for the degradation of a number of signaling molecules within the cell that may remove normal restraints on synaptic plasticity. We have used electrophysiology, in situ hybridization histochemistry, semiquantitative RT-PCR, Western blotting, and in vivo behavioral reflex analysis to investigate the ubiquitin-proteasome system in a model of neuropathic pain. In neuropathic animals, ionophoretic application of selective proteasome inhibitors attenuated dorsal horn neuron firing evoked by normally innocuous brush or cold stimuli and by noxious mustard oil stimuli. In control animals, only mustard oil-evoked responses were inhibited. Intrathecal administration of proteasome inhibitors attenuated hyperalgesia and allodynia in neuropathic rats. Expression of UCH-L1 (a rat homolog of Aplysia neuronal UCH and of the human UCH-L1, also known as PGP 9.5) and its mRNA were selectively increased within the ipsilateral dorsal horn of neuropathic rats, supporting the idea of a role for the ubiquitin-proteasome system in nociceptive processing. Proteasome inhibitors selectively attenuate allodynic and hyperalgesic responses in neuropathic pain, with some reduction in normal nociceptive, but not non-nociceptive responses, and potentially represent a novel therapeutic strategy for neuropathic pain.
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PMID:A role of the ubiquitin-proteasome system in neuropathic pain. 1185 Apr 63

Neuropathic pain is part of the neurological disease spectrum and may be an expression of severe medical pathology. Painful neuropathies have multiple disguises and may to a certain extent be mimicked by non-neurological pain conditions. Painful neuropathic conditions express themselves with spontaneous and/or abnormal stimulus-evoked pain. The diagnosis of peripheral or central neuropathic pain should be made only when the history and signs are indicative of neuropathy in conjunction with neuroanatomically correlated pain distribution and sensory abnormalities within the area of pain. A future mechanism-based classification of pain has recently been suggested to facilitate the development of mechanism-tailored treatment strategies. This is a sound approach and should be pursued. It is mandatory, however, to retain the traditional organ-based diagnostic workup, which should precede further in-depth characterization of specific pain mechanisms. Extensive preparatory work is needed on how to link certain symptoms and signs to specific mechanisms, as elucidated from animal studies, before we can introduce mechanism-coupled treatment strategies.
Eur J Pain 2002
PMID:Neuropathic pain: clinical characteristics and diagnostic workup. 1188 41

Neuropathic pain, whether of peripheral or central origin, is characterized by a neuronal hyperexcitability in damaged areas of the nervous system. In peripheral neuropathic pain, damaged nerve endings exhibit abnormal spontaneous and increased evoked activity, partly due to an increased and novel expression of sodium channels. In central pain, although not explored in detail, the spontaneous pain and evoked allodynia are also best explained by a neuronal hyperexcitability. The peripheral hyperexcitability is due to a series of molecular changes at the level of the peripheral nociceptor, in dorsal root ganglia, in the dorsal horn of the spinal cord, and in the brain. These changes include abnormal expression of sodium channels, increased activity at glutamate receptor sites, changes in gamma-aminobutyric acid (GABA-ergic) inhibition, and an alteration of calcium influx into cells. The neuronal hyperexcitability and corresponding molecular changes in neuropathic pain have many features in common with the cellular changes in certain forms of epilepsy. This has led to the use of anticonvulsant drugs for the treatment of neuropathic pain. Carbamazepine and phenytoin were the first anticonvulsants to be used in controlled clinical trials. Studies have shown these agents to relieve painful diabetic neuropathy and paroxysmal attacks in trigeminal neuralgia. Subsequent studies have shown the anticonvulsant gabapentin to be effective in painful diabetic neuropathy, mixed neuropathies, and postherpetic neuralgia. Lamotrigine, a new anticonvulsant, is effective in trigeminal neuralgia, painful peripheral neuropathy, and post-stroke pain. Other anticonvulsants, both new and old, are currently undergoing controlled clinical testing. The most common adverse effects of anticonvulsants are sedation and cerebellar symptoms (nystagmus, tremor and incoordination). Less common side-effects include haematological changes and cardiac arrhythmia with phenytoin and carbamazepine. The introduction of a mechanism-based classification of neuropathic pain, together with new anticonvulsants with a more specific pharmacological action, may lead to more rational treatment for the individual patient with neuropathic pain.
Eur J Pain 2002
PMID:Anticonvulsants in neuropathic pain: rationale and clinical evidence. 1188 43

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathies. Neuropathic pain is a common feature of many peripheral neuropathies including those associated with diabetes, uremia, HIV infection, and alcohol abuse. Pain is also present in the majority of patients with idiopathic sensory and sensorimotor polyneuropathies. A growing number of pharmacologic agents are available for the treatment of neuropathic pain. The medications that have undergone the most rigorous study are the tricyclic antidepressants and anticonvulsants. These two families of medications are widely used and represent first-line agents in the management of neuropathic pain. Pain management should begin with a concerted effort to identify the etiology of the neuropathy, as directed therapy may help alleviate the symptoms. When initiating pharmacotherapy for neuropathic pain, one must individualize treatment and choose an agent that is likely to be tolerated, as adverse events are not uncommon for some of the medications. Treatment of neuropathic pain remains challenging, with considerable variability in an individual's response to the various agents and even to different drugs in the same class. However, monotherapy with a well-chosen agent or rational polypharmacy that combines medications with different mechanisms of action will benefit a majority of patients with neuropathic pain.
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PMID:Painful Peripheral Neuropathy. 1193 24

Many patients with neuropathic pain have coexistent sensory deficits. Neuropathic pain may be alleviated by a variety of drugs but sensory deficits are assumed to be permanent. In an audit of the effects of gabapentin therapy on patients with neuropathic pain, monthly detailed sensory examinations were performed during the first three months of treatment. Of five patients with sensory deficits who tolerated gabapentin therapy, three showed marked improvement of their sensory deficits associated with pain alleviation. The cases are presented and possible explanations for the observed sensory improvements are discussed. These findings raised exciting neurophysiological questions in addition to being of potential importance to the clinical problem of neurotrophic tissue injury.
Pain 2002 Apr
PMID:Case reports - reversal of sensory deficit associated with pain relief after treatment with gabapentin. 1197 6


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