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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 has been suggested to be resistant to treatment with opiates. Such perceived lack of opioid responsiveness may be due to the dose-range over which specific opioid compounds have been studied as well as the efficacy of these compounds. Dihydroetorphine is a novel opiate that demonstrates significantly greater analgesic potency compared to morphine, and which also demonstrates diminished capacity for producing physical dependence in laboratory animals. The present study compared the intravenous (i.v.) efficacy, potency and duration of action of dihydroetorphine, fentanyl, heroin and morphine in producing anti-allodynic actions in a rat model of neuropathic pain (ligation of the L5/L6 nerve roots). All compounds produced significant anti-allodynic activity with dihydroetorphine being the most potent (A50 of 0.2 microg kg(-1), i.v.). Morphine was approximately 7440 times less potent than dihydroetorphine while heroin and fentanyl were approximately 163.5 and 6.9 times less potent in producing anti-allodynic actions. Dihydroetorphine also showed a maximal effect at 0.6 microg kg(-1) in all animals tested, while 100 microg kg(-1) was required for heroin to produce a maximal effect. Fentanyl and morphine did not elicit a maximum anti-allodynic response (74 and 76% maximum possible effect (%MPE), respectively). As expected, fentanyl showed a relatively brief duration of action (approximately 20 min at the highest tested dose), while dihydroetorphine and morphine demonstrated anti-allodynic actions for up to 45 min. Heroin had the longest duration of action, producing significant anti-allodynic effects for up to 90 min. These data show that dihydroetorphine and heroin produce potent and long-lasting anti-allodynic actions in this model. Additionally, in contrast to morphine and fentanyl, both dihydroetorphine and heroin were able to achieve a maximal response. The remarkable potency, maximal efficacy and duration of action of these compounds, particularly dihydroetorphine, suggests that these compounds may warrant further examination as potential therapeutic treatments for neuropathic pain states.
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PMID:Anti-allodynic actions of intravenous opioids in the nerve injured rat: potential utility of heroin and dihydroetorphine against neuropathic pain. 978 70

Neuropathic pain may be produced, at least in part, by the increased activity of primary afferent neurons. Studies have suggested that an accumulation of voltage-gated sodium channels at the site of peripheral nerve injury is a primary precursory event for subsequent afferent hyperexcitability. In this study, a human sodium channel (hPN3, SCN10A) has been cloned from the lumbar 4/5 dorsal root ganglia (DRG). Expression of hPN3 in Xenopus oocytes showed that this clone is a functional voltage-gated sodium channel. The amino acid sequence of hPN3 is most closely related to the rat PN3/SNS sodium channels which are expressed primarily in the small neurons of rat DRGs. The homologous relationship between rPN3 and hPN3 is defined by (i) a high level of sequence identity (ii) sodium currents that are highly resistant to tetrodotoxin (TTX) (iii) similar tissue distribution profiles and (iv) orthologous chromosomal map positions. Since rPN3/SNS has been implicated in nociceptive transmission, hPN3 may prove to be a valuable target for therapeutic agents against neuropathic pain.
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PMID:A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A. 983 20

Orofacial pain, especially if the problem is chronic, presents a diagnostic and management challenge to all health practitioners. This paper suggests how clinicians might simplify the diagnosis of orofacial pain. First, the pain is classified into one of the three basic pain categories: somatic, neuropathic, or psychogenic pain. Somatic pain results from noxious stimulation of normal neural structures. Neuropathic pain is caused by a structural abnormality in the nervous system. Psychogenic pain arises from psychic causes; there is no apparent physiologic or organic basis for the pain. The next step is to determine the tissue system from which the pain arises: intracranial, extracranial, musculoskeletal, neurovascular, neurogenous, or psychological. Finally, some of the more common orofacial pain syndromes within each category are discussed.
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PMID:Differential diagnosis of orofacial pain. 984 62

Neuropathic pain syndromes are one of the major problems of cancer pain treatment. The present study surveys 593 cancer patients treated by a pain service following the WHO guidelines for relief of cancer pain. Of these, 380 presented with nociceptive, 32 with neuropathic and 181 with mixed (nociceptive and neuropathic) pain. In patients with nociceptive, mixed and neuropathic pain, the average duration of evaluated pain treatment was 51, 53 and 38 days, respectively. Non-opioid or opioid analgesics were given to 99%, 96% and 79%, antidepressants to 8%, 25% and 19%, anticonvulsants to 2%, 22% and 38% and corticosteroids to 26%, 35% and 22% of patients, respectively. Systemic analgesia was supported by palliative antineoplastic treatment (48%, 56% and 38% of patients), nerve blocks (3%, 6% and 6%), psychotherapy (3%, 7% and 3%), physiotherapy (6%, 12% and 13%) and transcutaneous electric nerve stimulation (1%, 6% and 6%). Analgesic treatment resulted in a significant pain relief in all groups of patients, as the mean pain intensity (NRS) decreased from 66 (nociceptive), 65 (mixed) and 70 (neuropathic) on admission to 26, 30 and 28 after 3 days and 18, 17 and 21 at the end of survey. The total outcome of pain treatment was not predicted by the designation to nociceptive, mixed or neuropathic pain. In conclusion, neuropathic cancer pain is not intractable and can be relieved in the majority of patients by treatment following the WHO guidelines.
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PMID:Assessment and treatment of neuropathic cancer pain following WHO guidelines. 992 71

In nine patients with trigeminal neuropathic pain after nerve injury, we examined prospectively the effect of peripheral glycerol neurolysis on abnormal pain and sensory perception. In the painful facial skin area of these patients, we found increased temperature and tactile thresholds and the presence of abnormal temporal summation of pain. In seven patients, neuropathic pain was peripheral and disappeared after application of local anaesthesia at or proximal to the site of nerve injury. Neuropathic pain was central in two patients, and unresponsive to local anaesthesia applied proximal to the site of nerve injury. Six weeks after injection of glycerol proximal to the site of nerve injury, no or marginal pain relief was found in 8 patients with peripheral or central trigeminal neuropathic pain. On the other hand, in one of the patients with peripheral trigeminal neuropathic pain, glycerol was given at the site of nerve injury, and produced total pain relief for the whole observation period of 7 months. In this patient, pain relief was associated with normalisation of abnormal temporal summation of pain, which was not observed in the 8 patients with no or marginal pain relief. No further changes in temperature or tactile thresholds were found in any of the 9 patients after a single injection of absolute glycerol. Total pain relief in one of the patients probably is related to the ability of glycerol to inhibit ongoing ectopic impulse generation at the site of nerve injury. We suggest that glycerol-induced reduction of primary afferent hyperactivity may secondarily result in down-regulation of central neuronal hyperexcitability. The efficacy of application of glycerol at the site of nerve injury in patients with peripheral trigeminal neuropathic pain may warrant further investigation. However, this prospective study does not provide evidence that application of glycerol proximal to the site of nerve injury has a place in the treatment of trigeminal neuropathic pain.
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PMID:The effect of peripheral glycerol on trigeminal neuropathic pain examined by quantitative assessment of abnormal pain and sensory perception. 993 28

Pharmacologic treatments to manage chronic intractable pain have long been sought. Neuropathic pain is usually resistant to analgesics. At present, no analgesic drug totally relieves pain without producing significant unwanted side effects. Electrical stimulation can offer a degree of relief to some sufferers without risk. Transcutaneous electrical nerve stimulation (TENS) has a long clinical history. Stimulation parameters have been studied to improve the efficacy of this method. TENS is inadequate for extensive and bilateral pain, and epidural spinal cord stimulation is indicated. Dorsal column stimulation (DCS) initially was used to manage pain, but recent clinical reports show that it also can be effective in vascular disease and movement disorders. This review article reports on improvements in the electrical parameters used in neurostimulation and advances in research to overcome methodologic problems of DCS.
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PMID:Advances in electrical nerve stimulation techniques to manage chronic pain: an overview. 1014 24

Neuropathic pain is thought to arise from ectopic discharges at the site of injury within the peripheral nervous system, and is manifest as a general increase in the level of neuronal excitability within primary afferent fibres and their synaptic contacts within the spinal cord. Voltage-activated Na+ channel blockers such as lamotrigine have been shown to be clinically effective in the treatment of neuropathic pain. Na+ channels are structurally diverse comprising a principal a subunit (of which there are variable isoforms) and two auxiliary subunits termed beta1 and beta2. Both beta subunits affect the rates of channel activation and inactivation, and can modify alpha subunit density within the plasma membrane. In addition, these subunits may interact with extracellular matrix molecules to affect growth and myelination of axons. Using in situ hybridization histochemistry we have shown that the expression of the beta1 and beta2 subunits within the dorsal horn of the spinal cord of neuropathic rats is differentially regulated by a chronic constrictive injury to the sciatic nerve. At days 12-15 post-neuropathy, beta1 messenger RNA levels had increased, whereas beta2 messenger RNA levels had decreased significantly within laminae I, II on the ipsilateral side of the cord relative to the contralateral side. Within laminae III-IV beta2 messenger RNA levels showed a small but significant decrease on the ipsilateral side relative to the contralateral side, whilst expression of beta1 messenger RNA remained unchanged. Thus, differential regulation of the individual beta subunit types may (through their distinct influences on Na+ channel function) contribute to altered excitability of central neurons after neuropathic injury.
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PMID:The sodium channel auxiliary subunits beta1 and beta2 are differentially expressed in the spinal cord of neuropathic rats. 1018 42

Neuropathic pain is caused by lesions in the peripheral and/or central nervous system. Patients with pain due to nerve damage after operations are often misinterpreted and met with suspicion of malingering. Neuropathic pain typically presents with a characteristic set of sensory disorders independent of the cause. The sensory dysfunction may manifest itself as hypo- and/or hyperesthesia to one or more modalities, increased pain to painful stimuli (hyperalgesia) and/or pain to non-painful stimuli (allodynia). Conventional analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs and opioids are often ineffective. Instead, antidepressants and anticonvulsants may be tried. The pain condition is unknown to most physicians. This may result in mistreated patients having undergone several unnecessary and ineffective investigations and treatments.
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PMID:[Diagnosis and treatment of postoperative nerve damage. Chronic neuropathic pain]. 1048 32

A prospective, longitudinal study of 100 people with traumatic spinal cord injury (SCI) was performed to determine the time of onset. prevalence and severity of different types of pain (musculoskeletal, visceral, neuropathic at level, neuropathic below level) at 2, 4, 8, 13 and 26 weeks following SCI. In addition, we sought to determine the relationship between physical factors such as level of lesion, completeness and clinical SCI syndrome and the presence of pain. At 6 months following SCI, 40% of people had musculoskeletal pain, none had visceral pain, 36% had neuropathic at level pain and 19% had neuropathic below level pain. When all types of pain were included, at 6 months following injury, 64% of people in the study had pain, and 21% of people had pain that was rated as severe. Those with neuropathic below level pain were most likely to report their pain as severe or excruciating. There was no relationship between the presence of pain overall and level or completeness of lesion, or type of injury. Significant differences were found, however, when specific types of pain were examined. Musculoskeletal pain was more common in people with thoracic level injuries. Neuropathic pain associated with allodynia was more common in people who had incomplete spinal cord lesions, cervical rather than thoracic spinal cord lesions, and central cord syndrome. Therefore, this study suggests that most people continue to experience pain 6 months following spinal cord injury and 21% of people continue to experience severe pain. While the presence or absence of pain overall does not appear to be related to physical factors following SCI, there does appear to be a relationship between physical factors and pain when the pain is classified into specific types.
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PMID:Pain report and the relationship of pain to physical factors in the first 6 months following spinal cord injury. 1035 7

The possible role of spinal prostanoids in the tactile allodynia and thermal hyperalgesia associated with an experimental model of neuropathic pain was investigated. Neuropathic pain was induced by tight ligation of the L5 and L6 spinal nerves. Tactile allodynia was assessed 7 days after the surgery by measuring hindpaw withdrawal threshold to probing with von Frey filaments. Thermal hyperalgesia and nociception were determined by the 52 degrees C warm-water tail-flick test and by applying radiant heat to the plantar aspect of the hindpaw ipsilateral to the ligation. Minimal antiallodynic effect was produced by intrathecal (i.th.) administration of ketorolac or morphine up to the highest testable dose (100 microg) or by the (R)- or (S)-enantiomers of ketorolac (up to 6 microg) when administered alone. However, i.th. administration of a fixed ratio (1:1) of morphine plus racemic ketorolac or of morphine plus the (S)-enantiomer of ketorolac (S-ketorolac) produced a dose- and time-related antiallodynic effect: ED50 114 +/- 35.9 microg (total dose) for morphine plus ketorolac and 70.5 +/- 21.0 microg (total dose) for morphine plus S-ketorolac. The combination of i.th. morphine plus the (R)-enantiomer of ketorolac (R-ketorolac) (up to 200 microg total dose) was without effect. Similar antiallodynic activity was obtained for the co-administration of i.th. morphine and intravenous (i.v.) racemic ketorolac. In order to investigate the role of cyclooxygenase (COX) isozymes, relatively selective COX1 (piroxicam) and COX2 N-[2-cyclohexyloxy-4-nitrophenyl] metanesulfonamide (NS-398) inhibitors were administered i.th. (60 microg) alone or together with i.th. morphine. Piroxicam, NS-398, morphine and vehicle (90% DMSO) were without significant antiallodynic effect when administered alone, but moderate antiallodynic effects were produced by i.th. administration of fixed ratio (1:1) combinations of morphine with 60 microg each (highest soluble dose) of piroxicam (%MPE = 40.8 +/- 10.2) or NS-398 (%MPE = 32.4 +/- 9.5). Further, the combined i.th. administration of morphine, piroxicam and NS-398 in fixed 1:1:1 ratio (60 microg each) resulted in a supraadditive antiallodynic effect (%MPE = 70.4 +/- 10.8). Finally, morphine, but not ketorolac, given i.th. produced dose-dependent anti nociception in either the tail-flick or the paw-flick tests. However, there was no synergy between morphine and ketorolac against thermal nociception in either of the tests. These findings suggest that spinal prostanoids produced via both COX1 and COX2 pathways may play a role in neuropathic pain states and suggest the clinical utility of opioid plus COX-inhibitor combination therapy.
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PMID:Synergistic antiallodynic effects of spinal morphine with ketorolac and selective COX1- and COX2-inhibitors in nerve-injured rats. 1042 61


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