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)

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

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed medications worldwide. Diclofenac sodium (DS), one of these NSAIDs, has a high specificity for arachidonic acid-degrading cyclooxygenase (COX)-2 enzymes. This drug can be used to relieve neuropathic pain. In this review, we examine the relevant researches, including in vivo, animal, and clinical human studies, with the aim of understanding the effect of DS on the peripheral nerves. In injured nerves, COX-2 is potently upregulated around the injury site. When a nerve is damaged, both COX-1 and COX-2 expression is increased in macrophages and Schwann cells. In addition, COX inhibitors can promote axonal outgrowth in cultured neurons. Neuropathic pain occurs after injury and leads to dysfunction of the peripheral nervous system. NSAIDs can modulate the nociceptive and inflammatory pain pathways and control neuropathic pain. DS may accelerate nerve regeneration and its effects on healing, as well as causing deleterious effects in the developing nerves. DS teratogenicity disrupts myelin sheath thickness and axon structure. Understanding the possible benefits and limitations of DS and specific conditions such as prenatal use will be of benefit in clinical practice.
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PMID:Peripheral nerve and diclofenac sodium: Molecular and clinical approaches. 2887 Jul 62