Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drugs that are clinically effective (mexiletine and desipramine) or ineffective (fluoxetine) in the treatment of human neuropathic pain were evaluated for efficacy in rat models involving central sensitization (i.e., formalin model and the L5/L6 spinal nerve ligation model of neuropathic pain) using tests that differ in stimulus modality: noxious chemical stimulus (formalin model) as well as noxious (pin prick) and innocuous mechanical stimuli (application of von Frey filaments). Mexiletine (10-100 mg/kg, s.c.) significantly (P < 0.05) attenuated hyperalgesia in formalin-treated (60 mg/kg and 100 mg/kg) and neuropathic rats (100 mg/kg) as well as tactile allodynia in neuropathic rats (100 mg/kg). Desipramine (1-100 mg/kg, s.c.), on the other hand, reduced hyperalgesia significantly (P < 0.05) in formalin-treated (3, 10, 30 and 100 mg/kg) and neuropathic rats (10 mg/kg and 100 mg/kg), but did not reduce tactile allodynia in the neuropathic rats. Fluoxetine (3-30 mg/kg, s.c.) did not inhibit either hyperalgesia or allodynia in any of the tests employed. Fluoxetine, which is relatively ineffective in reducing neuropathic pain in humans, was also ineffective in reducing hyperalgesia and allodynia associated with central sensitization in rats. Thus, drugs which are effective in reducing human neuropathic pain consistently attenuated hyperalgesia in formalin-treated or neuropathic rats. Desipramine also distinguished mechanical hyperalgesia from tactile allodynia in rats rendered neuropathic by spinal nerve ligation. These data are consistent with the hypothesis that the neuronal mechanisms underlying these two manifestations of neuropathic pain are different.
 ...
PMID:The effects of mexiletine, desipramine and fluoxetine in rat models involving central sensitization. 906 27

Mexiletine is widely used for the treatment of neuropathic pain although its site(s) of action remain unclear. Here we have studied the effect of spinal administration of mexiletine (10-1000 microg) on the spontaneous and peripherally evoked responses of spinal neurones of nerve injured (selective ligation of spinal nerves L5-L6; SNL) rats. Sham controls for the surgical intervention were performed. A high proportion of the spinal neurones of SNL rats exhibited de novo spontaneous activity (mean frequency of firing 4+/-1 Hz), this activity was highly sensitive to spinal mexiletine (F5,55 = 2.5, P < or = 0.05). The spinal neurones of the sham operated rats exhibited negligible spontaneous activity. The electrically evoked Abeta-fibre neuronal responses of SNL and sham operated rats were not significantly influenced by spinal mexiletine. In contrast, the Adelta-fibre and C-fibre evoked neuronal responses of the SNL rats, but not sham operated rats, were significantly reduced by spinal mexiletine (F5.52 = 4.9, P < or = 0.001 and F5,48 = 12, P < or = 0.0001, respectively). In addition, the mechanical punctate von Frey 9 and 50 g evoked neuronal responses of the SNL rats, but not sham operated rats, were significantly reduced by spinal mexiletine (F5,57 = 4.3, P < or = 0.002 and F5,52 = 6.1, P < or = 0.001). This pharmacological study suggests that following nerve injury there is a novel mexiletine sensitive spinal substrate which contributes to Adelta-fibre and C-fibre, but not Abeta-fibre, somatosensory transmission. This central action may underlie some of the clinical efficacy of mexiletine in the treatment of neuropathic pain states.
 ...
PMID:A novel spinal action of mexiletine in spinal somatosensory transmission of nerve injured rats. 980 54

The present study was designed to investigate the anti-allodynic effects of current analgesic agents, such as pregabalin, amitriptyline, mexiletine, morphine, and diclofenac, in a rat model of streptozotocin (STZ)-induced diabetic neuropathy. Diabetic rats developed a sustained decrease in withdrawal threshold response to the von Frey test within 8 weeks after a single injection of STZ (45 mg/kg, i.v.). The anti-allodynic effects of analgesic agents were examined after a single oral or subcutaneous administration at 3 and 7 weeks after beginning of STZ-treatment. Pregabalin (3-30 mg/kg, p.o.), an antiepileptic agent, dose-dependently blocked the mechanical allodynia in rats treated both at 3 and 7 weeks. Mexiletine (10-100 mg/kg, p.o.), a sodium channel blocker, dose-dependently ameliorated mechanical allodynia in rats treated at 3 weeks; however, the efficacy was diminished at 7 weeks. Morphine (1-10 mg/kg, s.c.) was effective in rats treated at 3 weeks; however, it was ineffective at 7 weeks. Conversely, an antidepressant amitriptyline (0.3-3 mg/kg, p.o.) improved mechanical allodynia in rats treated at 7 weeks, whereas it was ineffective at 3 weeks. Diclofenac, a non-steroidal anti-inflammatory drug, was ineffective at both time points. These results demonstrate that, except for diclofenac, the standard analgesic agents tested can effectively alleviate the mechanical allodynia seen in STZ-induced diabetic neuropathy. Their efficacies varied depending on the duration of the diabetic condition, suggesting that temporal changes in pharmacodynamic factors could affect the responsiveness of this model to analgesic agents.
 ...
PMID:Pharmacological characterization of standard analgesics on mechanical allodynia in streptozotocin-induced diabetic rats. 1959 53