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1.
Melatonin reduces formalin-induced nociception and tactile allodynia in diabetic rats 总被引:2,自引:1,他引:1
Arreola-Espino R Urquiza-Marín H Ambriz-Tututi M Araiza-Saldaña CI Caram-Salas NL Rocha-González HI Mixcoatl-Zecuatl T Granados-Soto V 《European journal of pharmacology》2007,577(1-3):203-210
The purpose of this study was to assess the antinociceptive and antiallodynic effect of melatonin as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral administration of melatonin (10-300 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. In addition, K-185 (a melatonin MT(2) receptor antagonist, 0.2-2 mg/kg, s.c.) completely blocked the melatonin-induced antinociception in diabetic rats, whereas that naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) and naltrindole (a selective delta opioid receptor antagonist, 0.5 mg/kg, s.c.), but not 5'-guanidinonaltrindole (a selective kappa opioid receptor antagonist, 1 mg/kg, s.c.), partially reduced the antinociceptive effect of melatonin. Given alone K-185, naltrexone, naltrindole or 5'-guanidinonaltrindole did not modify formalin-induced nociception in diabetic rats. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of melatonin (75-300 mg/kg) dose-dependently reduced tactile allodynia in diabetic rats. Both antinociceptive and antiallodynic effects were not related to motor changes as melatonin did not modify number of falls in the rotarod test. Results indicate that melatonin is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that melatonin MT(2) and delta opioid receptors may play an important role in these effects. 相似文献
2.
Benfotiamine relieves inflammatory and neuropathic pain in rats 总被引:3,自引:0,他引:3
Sánchez-Ramírez GM Caram-Salas NL Rocha-González HI Vidal-Cantú GC Medina-Santillán R Reyes-García G Granados-Soto V 《European journal of pharmacology》2006,530(1-2):48-53
Benfotiamine has shown therapeutic efficacy in the treatment of painful diabetic neuropathy in human beings. However, so far there is no evidence about the efficacy of this drug in preclinical models of pain. The purpose of this study was to assess the possible antinociceptive and antiallodynic effect of benfotiamine in inflammatory and neuropathic pain models in the rat. Inflammatory pain was induced by injection of formalin in non-diabetic and diabetic (2 weeks) rats. Reduction of flinching behavior was considered as antinociception. Neuropathic pain was induced by either ligation of left L5/L6 spinal nerves or administration of streptozotocin (50 mg/kg, i.p.) in Wistar rats. Benfotiamine significantly reduced inflammatory (10-300 mg/kg) and neuropathic (75-300 mg/kg) nociception in non-diabetic and diabetic rats. Results indicate that oral administration of benfotiamine is able to reduce tactile allodynia from different origin in the rat and they suggest the use of this drug to reduce inflammatory and neuropathic pain in humans. 相似文献
3.
Guadalupe del Carmen Baeza-Flores Erick J. Rodríguez-Palma Valeria Reyes-Pérez Crystell G. Guzmán-Priego Jorge E. Torres-López 《Drug development research》2020,81(6):728-735
Ceftriaxone (CFX) is a β-lactam antibiotic with analgesic properties. However, its role in the formalin-induced nociception remains unknown. The purpose of this study was to investigate the antinociceptive effect of CFX in the 1% formalin test in rats. Formalin induced a typical nociceptive response (flinching behavior) of two phases. Local peripheral pretreatment (20 min) with CFX (400–800 μg/paw) slightly attenuated the flinching behavior in phase 2, but not phase 1. Acute intraperitoneal pretreatment (20 min) also reduced phase 2 of the formalin test. In both cases, CFX induced a dose-dependent antinociception. We also tested the effect of CFX 1 day after its administration and in two schedules of repeated administration. One-day pretreatment with CFX (50–400 mg/kg, ip) induced a dose-dependent antinociceptive effect in formalin-treated rats. Repeated administration (daily during 3 or 7 days) with CFX (50–400 mg/kg, ip) diminished formalin-induced nociception. Results suggest that local or systemic as well as single or repeated administration of CFX reduces formalin-induced nociception. 相似文献
4.
Bermúdez-Ocaña DY Aguilar-Mariscal H Frías TR Blé-Castillo JL Flores-Murrieta FJ Díaz-Zagoya JC Granados-Soto V Juárez-Rojop IE 《European journal of pharmacology》2011,664(1-3):8-13
The purpose of this study was to assess the effect of the non-selective cholecystokinin receptor antagonist proglumide on the antinociceptive activity of ketorolac and meloxicam in non-diabetic and diabetic rats. Streptozotocin (60 mg/kg) injection caused hyperglycemia which was maintained for 2 weeks. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Local peripheral ipsilateral, but not contralateral, administration of ketorolac and meloxicam produced antinociception in non-diabetic and diabetic rats. However, the antinociceptive effect of both drugs was significantly reduced in diabetic animals. Proglumide was ineffective by itself and it did not affect the antinociception induced by the cyclooxygenase inhibitors in non-diabetic rats. Contrariwise, proglumide reduced formalin-induced nociception and it increased ketorolac- or meloxicam-induced antinociception in diabetic rats. These results suggest that peripheral cholecystokinin plays an important role in diabetes-induced sensitization as well as in the reduction of the antinociceptive effects of ketorolac and meloxicam in diabetic rats. The combination of cholecystokinin receptor antagonists and ketorolac or meloxicam may be a useful strategy to reduce nociception in diabetic patients. 相似文献
5.
《Drug development research》2017,78(8):371-380
Preclinical Research |
6.
Fosinopril Prevents the Development of Tactile Allodynia in a Streptozotocin‐Induced Diabetic Rat Model
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Claudia Ivonne Araiza‐Saldaña Erick Fabián Pedraza‐Priego Jorge Elías Torres‐López Héctor Isaac Rocha‐González Gabriela Castañeda‐Corral Enrique Hong‐Chong Vinicio Granados‐Soto 《Drug development research》2015,76(8):442-449
Preclinical Research |
7.
ABT-627, an endothelin ET(A) receptor-selective antagonist, attenuates tactile allodynia in a diabetic rat model of neuropathic pain 总被引:5,自引:0,他引:5
Jarvis MF Wessale JL Zhu CZ Lynch JJ Dayton BD Calzadilla SV Padley RJ Opgenorth TJ Kowaluk EA 《European journal of pharmacology》2000,388(1):29-35
Tactile allodynia, the enhanced perception of pain in response to normally non-painful stimulation, represents a common complication of diabetic neuropathy. The activation of endothelin ET(A) receptors has been implicated in diabetes-induced reductions in peripheral neurovascularization and concomitant endoneurial hypoxia. Endothelin receptor activation has also been shown to alter the peripheral and central processing of nociceptive information. The present study was conducted to evaluate the antinociceptive effects of the novel endothelin ET(A) receptor-selective antagonist, 2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N, N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (ABT-627), in the streptozotocin-induced diabetic rat model of neuropathic pain. Rats were injected with 75 mg/kg streptozotocin (i. p.), and drug effects were assessed 8-12 weeks following streptozotocin treatment to allow for stabilization of blood glucose levels (>/=240 mg/dl) and tactile allodynia thresholds (=8.0 g). Systemic (i.p.) administration of ABT-627 (1 and 10 mg/kg) was found to produce a dose-dependent increase in tactile allodynia thresholds. A significant antinociceptive effect (40-50% increase in tactile allodynia thresholds, P<0.05) was observed at the dose of 10 mg/kg, i.p., within 0.5-2-h post-dosing. The antinociceptive effects of ABT-627 (10 mg kg(-1) day(-1), p.o.) were maintained following chronic administration of the antagonist in drinking water for 7 days. In comparison, morphine administered acutely at a dose of 8 mg/kg, i.p., produced a significant 90% increase in streptozotocin-induced tactile allodynia thresholds. The endothelin ET(B) receptor-selective antagonist, 2R-(4-propoxyphenyl)-4S-(1, 3-benzodioxol-5-yl)-1-(N-(2, 6-diethylphenyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxy lic acid (A-192621; 20 mg/kg, i.p.), did not significantly alter tactile allodynia thresholds in streptozotocin-treated rats. Although combined i.p. administration of ABT-627 and A-192621 produced a significant, acute increase in tactile allodynia thresholds, this effect was significantly less than that produced by ABT-627 alone. These results indicate that the selective blockade of endothelin ET(A) receptors results in an attenuation of tactile allodynia in the streptozotocin-treated rat. 相似文献
8.
Mixcoatl-Zecuatl T Quinonez-Bastidas GN Caram-Salas NL Ambriz-Tututi M Araiza-Saldana CI Rocha-Gonzalez HI Medina-Santillan R Reyes-Garcia G Granados-Soto V 《Methods and findings in experimental and clinical pharmacology》2008,30(6):431-441
Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans. 相似文献
9.
Barua CC Roy JD Buragohain B Barua AG Borah P Lahkar M 《Indian journal of pharmacology》2011,43(2):121-125
Objectives:
To study the analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd.Materials and Methods:
Wistar rats and Swiss albino mice were used for studying analgesic and anti-nociceptive activity of Drymaria cordata hydroethanolic extract (DCHE) at doses 50, 100 and 200 mg/kg p.o. Various models viz. acetic acid induced writhing model (female mice), Eddy''s hot plate (mice) and tail flick model (rat) for analgesic study and formalin-induced paw licking model (mice) were used for anti-nociceptive study.Results:
In acetic acid induced writhing model, effect of DCHE was better than the standard drug- indomethacin 10 mg/kg (p.o.). In the hot plate model, the maximum effect was observed at 60 min at a dose of 200 mg/kg p.o., which was higher than the standard drug morphine sulfate (1.5 mg/kg i.p.), whereas in the tail flick model, effect was comparable with morphine sulfate. In formalin-induced paw licking model, administration of DCHE completely abolished the early phase at 100 and 200 mg/kg p.o. and in the late phase, the effect of DCHE (200 mg/kg p.o.) was higher than indomethacin (10 mg/kg p.o.).Conclusion:
DCHE was effective in both non-narcotic and narcotic models of nociception, suggesting its possible action via peripheral and central mechanism. It also abolished the early phase in formalin-induced paw licking model, suggesting complete inactivation of C-fiber at higher dose. The activity can be attributed to the phyto-constituents viz tannins, diterpenes, triterpenes and steroids present in the DCHE extract. In conclusion, DCHE can be developed as a potent analgesic and anti-nociceptive agent in future. 相似文献10.
Effect of dipyrone and thalidomide alone and in combination on STZ-induced diabetic neuropathic pain
Diabetic neuropathy is recognized as one of the most common complications of chronic diabetes, but its pathophysiological
mechanism is complex and yet to be completely explored. Monotherapy with conventional analgesics fails to provide adequate
pain relief in peripheral diabetic neuropathy. There are a number of evidence suggesting that tumor necrosis factor (TNF-α)
plays an important role in the pathogenesis of peripheral diabetic neuropathy. TNF-α up-regulation activates nuclear factor
κB, which further up-regulates cyclooxygenase (COX)-2 leading to altered prostaglandin profile. Inhibition of TNF-α and COX-2
provides beneficial effect on diabetic neuropathy by decreasing the oxidative stress level and by preventing neuronal hypersensitivity
due to an increased prostaglandin level. The present study was designed to assess the effect of dipyrone and thalidomide on
streptozotocin (STZ)-induced neuropathic pain behavior in rats. STZ 50 mg/kg, i.p. was administered to induce experimental
diabetes in the rats. Three weeks following STZ, dipyrone (300 and 600 mg/kg, i.p.) and thalidomide (25 and 50 mg/kg, i.p.)
alone and subeffective dose combination of dipyrone and thalidomide (300 and 25 mg/kg−1, i.p.) administered daily for 2 weeks significantly attenuated thermal hyperalgesia, mechanical allodynia, and formalin-induced
phase-2 flinching response. Moreover, the subeffective dose combination of dipyrone and thalidomide and preemptive treatment
with thalidomide (50 mg/kg) reduces oxidative stress in diabetic rats. In conclusion, the combination of subeffective dose
of dipyrone and thalidomide prevented the development and maintenance of experimental diabetic neuropathy. The combination
of thalidomide (TNF-α inhibitor) and dipyrone (COX inhibitor) may be used as a potential therapeutic agent for the treatment
of diabetic neuropathy. 相似文献
11.
Ambriz-Tututi M Sánchez-González V Drucker-Colín R 《European journal of pharmacology》2011,668(1-2):147-154
In the present study, the effect of chromaffin cell transplant in the spinal cord was evaluated on formalin-induced mechanical secondary allodynia in the rat. Chromaffin cells were transplanted into the lumbar subarachnoid space before or after formalin injection. Subcutaneous formalin injection (50 μl, 1%) produced long-lasting secondary allodynia in the ipsilateral and contralateral hind paws. Once secondary allodynia was established, treatment with chromaffin cells produced a significant reduction in the nociceptive behavior in both hind paws. The antiallodynic effect was time-dependent since it was observed 15 days after chromaffin cell transplants but not before. On the other hand, pre-treatment with chromaffin cells prevented the expression of secondary allodynia in both hind paws in the rat. Antiallodynic effect of chromaffin cells was reverted with the non-selective opioid receptor antagonist naltrexone and the non-selective α(2)-adrenoceptor antagonist rauwolscine. Clusters of viable chromaffin cells labeled with anti-tyrosine hydroxylase antibodies were observed in the retrieved transplants 15 days after transplant. These results establish the analgesic efficacy of intrathecal chromaffin cells on formalin-induced secondary allodynia. Our data suggest that chromaffin cells release neuroactive substances including opioid peptides and adrenergic amines that reduce secondary allodynia in rats through activation of their receptors. 相似文献
12.
Naltrexone's influence on neurobehavioral development 总被引:1,自引:0,他引:1
The ontogeny of spontaneous motor and sensorimotor behaviors of preweaning rats, as well as ambulation, emotionality, and nociception at weaning (day 21), were studied in rats given chronic administration of 1 or 50 mg/kg naltrexone from birth to day 21. The age at which a specific spontaneous motor behavior or performance initially appeared and the age at which 100% of the animals demonstrated a particular behavior were accelerated in animals given 50 mg/kg naltrexone, but delayed in rats injected with 1 mg/kg naltrexone. In general, ambulation, emotionality, and nociceptive responses were not affected by naltrexone treatment, although the frequency of face-washing in both naltrexone groups and activity cage performance in the 50 mg/kg naltrexone group deviated from control levels. Observations of head-shake and wet-dog shake behaviors in naltrexone-treated animals at 2 hr and 10 hr post-drug injection were similar to controls with the exception of an abnormal increase in the 1 mg/kg naltrexone group at 10 hr. Although these results may imply that endogenous opioid systems play a role in regulating neurobehavioral development, further study is needed to distinguish whether these changes are a consequence of the somatic and morphological alterations known to occur with naltrexone administration or if the timetable of behavioral ontogeny is governed by endorphin-opiate receptor interaction. 相似文献
13.
Influence of felbamate on the antinociceptive action of morphine, metamizol and indomethacin in mice
The influence of felbamate (200 mg/kg or 50 mg/kg) on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg or 1.4 mg/kg) was investigated in a mouse model using the hot-plate test. All drugs were injected intraperitoneally. Felbamate was administered to mice 30 min before applying the analgesic drugs. Measurement of nociception was performed within 2 h after felbamate administration. The research studies were further conducted with a multiple (10 days) drug dosage. Felbamate in the dose of 200 mg/kg significantly increases the analgesic effect of morphine and weakens the effect of metamizol and indomethacin. Multiple administration of felbamate does not affect the activity of morphine and metamizol, but decreases analgesic effect of indomethacin. 相似文献
14.
《European journal of pharmacology》1999,364(2-3):141-146
The present study was conducted to characterize the development of tactile allodynia in the streptozotocin-induced rat model of diabetes, and to evaluate the antinociceptive effects of systemically administered morphine and the adenosine kinase inhibitor, 5′-deoxy-5-iodotubercidin (5′d-5IT) in this model. Rats were injected with 75 mg/kg streptozotocin (i.p.), and blood glucose levels were determined 3–4 weeks later. Diabetic (blood glucose levels≥250 mg/dl) and vehicle-injected rats were examined weekly for the development of tactile allodynia by measuring the threshold for hind paw withdrawal using von Frey hairs. Withdrawal thresholds were reduced to 6.8±0.6 g (mean±S.E.M.) in approximately one-third of streptozotocin-treated rats 7 weeks after streptozotocin treatment as compared to control thresholds (13.2±0.1 g), and this allodynia persisted for at least an additional 7 weeks. In additional experiments, morphine sulfate (5–21 μmol/kg, i.p.) produced dose-dependent antinociceptive effects on tactile allodynia for up to 2 h post-dosing. The adenosine kinase inhibitor, 5′d-5IT (2.5 and 5 μmol/kg, i.p.) also dose-dependently attenuated tactile allodynia. Pretreatment with the opioid receptor antagonist, naloxone (27 μmol/kg, i.p.) or the non-selective adenosine receptor antagonist, theophylline (111 μmol/kg, i.p.) significantly diminished the anti-allodynic effects of morphine and 5′d-5IT, respectively. The present study demonstrates that the potent and selective adenosine kinase inhibitor, 5′d-5IT, is equally effective as morphine in blocking tactile allodynia in this model. 相似文献
15.
Luis F. Ortega‐Varela Jorge E. Herrera Nadia L. Caram‐Salas Hector I. Rocha‐Gonzalez Jorge E. Torres‐López Vinicio Granados‐Soto 《Drug development research》2009,70(5):386-394
This study was designed to evaluate the possible antiallodynic interaction between metamizol and gabapentin in rats submitted to L5/L6 spinal nerve ligation. Metamizol, gabapentin, or a combination of both drugs were assessed after oral and intrathecal administration in neuropathic rats. Metamizol partially reduced tactile allodynia after intrathecal, but not oral, administration. Conversely, gabapentin reduced tactile allodynia in a dose‐dependent manner after both administration routes. Oral administration of a constant dose of metamizol (600 mg/kg) significantly increased the gabapentin‐induced antiallodynic effect. Moreover, the gabapentin ED50 value was lower in the presence than in the absence of metamizol. Intrathecal co‐administration of metamizol and gabapentin in a dose‐fixed ratio (0.5:0.5) reduced tactile allodynia in rats. The theoretical ED30 value for the spinal combination estimated from the isobologram was 118.4±12 µg, whereas that experimental ED30 value was 66.2±10.1 µg indicating a synergistic interaction. Results indicate that metamizol, a cyclo‐oxygenase 2 inhibitor, is able to reduce tactile allodynia as well to increase the antiallodynic effect of gabapentin in the neuropathic rat. This combination could be useful to treat neuropathic pain in humans. Drug Dev Res 2009. © 2009 Wiley‐Liss, Inc. 相似文献
16.
Evaluation of the anti-inflammatory, anti-nociceptive and gastric effects of Ginkgo biloba in the rat. 总被引:2,自引:0,他引:2
Omar M E Abdel-Salam Ayman R Baiuomy Seham El-batran Mahmoud S Arbid 《Pharmacological research》2004,49(2):133-142
Ginkgo biloba extract (GbE) was assessed in models of acute inflammation induced by carrageenan, formalin or capsaicin in the rat, in models of nociceptive pain, such as hot-plate (55 degrees C) latency, tail-electric stimulation assay and capsaicin-induced paw licking and in the model of acute gastric damage induced by indomethacin. The agent showed marked anti-inflammatory activity in the carrageenan model of paw oedema. When given subcutaneously (s.c.) (25 and 50 mg kg(-1)) 30 min before challenge, GbE inhibited paw oedema with a maximal effect of 43.7 and 56.9%, respectively, at 2h post-carrageenan. Significant inhibition of oedema was also observed when GbE (50 mg kg(-1), s.c.) was given 30 min after carrageenan challenge. The agent was also active p.o. in acute inflammation caused by carrageenan. The administration of GbE with indomethacin, rofecoxib, celecoxib, dexamethasone or melatonin resulted in an additive effect. GbE (50 mg kg(-1), s.c.) caused significant inhibition of formalin-induced paw oedema, but did not reduce the capsaicin-induced paw oedema. In tests of nociception, GbE (25, 50 or 100 mg kg(-1)) decreased in dose-dependent manner the capsaicin-induced hind paw licking time and was similarly effective in the hot-plate assay of nociception. In contrast, when assessed in the tail-electric stimulation test, GbE was only effective in the highest dose (100 mg kg(-1)). In pylorus-ligated rats, GbE (25 or 50 mg kg(-1)) increased gastric acid secretion, but reduced gastric mucosal damage caused by IND. Results suggest that GbE may be of clinical value as an anti-inflammatory and analgesic drug alone or in conjunction with NSAIDs. 相似文献
17.
Analysis of the mechanism underlying the peripheral antinociceptive action of sildenafil in the formalin test 总被引:1,自引:0,他引:1
Ambriz-Tututi M Velázquez-Zamora DA Urquiza-Marín H Granados-Soto V 《European journal of pharmacology》2005,512(2-3):121-127
The mechanism of the antinociceptive action of the phosphodiesterase 5 inhibitor, sildenafil, was assessed in the formalin test. Local peripheral ipsilateral, but not contralateral, administration of sildenafil (50-200 microg/paw) produced a dose-related antinociception during both phases of the formalin test. The local peripheral pretreatment with protein kinase G inhibitor peptide (PKG inhibitor, 0.01-1 microg/paw), charybdotoxin (large- and intermediate-conductance Ca2+-activated K+ channel blocker, 0.01-1 microg/paw), apamin (small-conductance Ca2+-activated K+ channel blocker, 0.1-2 microg/paw), tolbutamide (ATP-sensitive K+ channel blocker, 12.5-50 microg/paw), and tetraethylammonium (non-selective voltage-dependent K+ channel blocker, 12.5-50 microg/paw), but not 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, inhibitor of guanylyl cyclase, 12.5-50 microg/paw) or saline, significantly diminished in a dose-dependent manner sildenafil-induced local peripheral antinociception. Given alone, local peripheral administration of inhibitors did not modify formalin-induced nociceptive behavior. Results suggest that sildenafil produces its local peripheral antinociceptive effect via activation of the cyclic GMP-PKG-K+ channel pathway. 相似文献
18.
Bermúdez-Ocaña DY Ambriz-Tututi M Pérez-Severiano F Granados-Soto V 《Pharmacology, biochemistry, and behavior》2006,84(3):535-542
The possible participation of the nitric oxide (NO)-cyclic GMP-protein kinase G (PKG)-K+ channels pathway in the antiallodynic action of resveratrol and YC-1 in spinal nerve injured rats was assessed. Ligation of L5/L6 spinal nerves produced a clear-cut tactile allodynia in the rats. Intrathecal administration of resveratrol (100-600 microg) and 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (0.1-2.7 microg, YC-1, a soluble guanylyl cyclase activator) decreased tactile allodynia induced by ligation of L5/L6 spinal nerves. Intrathecal treatment with NG-L-nitro-arginine methyl ester (10-100 microg, L-NAME, a NO synthase inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (1-10 microg, ODQ, a soluble guanylyl cyclase inhibitor), KT-5823 (5-500 ng, a PKG inhibitor) and iberiotoxin (5-500 ng, a large-conductance Ca2+ -activated K+ channel blocker), but not NG-D-nitro-arginine methyl ester (100 microg, D-NAME, an inactive isomer of L-NAME), glibenclamide (12.5-50 microg, ATP-sensitive K+ channel blocker) or vehicle, significantly diminished resveratrol (300 microg)- and YC-1 (2.7 microg)-induced spinal antiallodynia. These effects were independent of prostaglandin synthesis inhibition as indomethacin did not affect resveratrol-induced antiallodynia. Results suggest that resveratrol and YC-1 could activate the proteins of the NO-cyclic GMP-PKG spinal pathway or large-conductance Ca2+ -activated, but not ATP-sensitive, K+ channels at the spinal cord in order to produce at least part of their antiallodynic effect in this model of neuropathy. 相似文献
19.
Thiamine and cyanocobalamin relieve neuropathic pain in rats: synergy with dexamethasone 总被引:1,自引:0,他引:1
Treatment of neuropathic pain is an area of largely unmet medical need. Therefore, this pain may require the development of novel drug entities. In the search for alternatives, B vitamins have been found to be a clinically useful pharmacological tool for patients with neuropathic pain. However, preclinical studies supporting this use are lacking. In this study, we assessed the possible antiallodynic effects of thiamine, pyridoxine, and cyanocobalamin as well as dexamethasone and their combination on spinal nerve ligation induced allodynia. Sub cutaneous administration of thiamine (75-600 mg/kg), pyridoxine (75-600 mg/kg), cyanocobalamin(0.75-6 mg/kg), and dexamethasone (4-32 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with 600 mg/kg of thiamine (approximately 58%), 600 mg/kg of pyridoxine (approximately 22%), 6 mg/kg of cyanocobalamin (approximately 73%), and 32 mg/kg of dexamethasone (approximately 68%). Since a small antiallodynic effect was observed with pyridoxine, this drug was not further analyzed in the combinations. Coadministration of thiamine or cyanocobalamin and dexamethasone remarkably reduced spinal nerve ligation induced allodynia (approximately 90%), showing a synergistic interaction between either thiamine or cyanocobalamin and dexamethasone. Our data indicate that thiamine and pyridoxine as well as the combination of B vitamins and dexamethasone are able to reduce tactile allodynia in rats and suggest the possible clinical use of these drugs in the treatment of neuropathic pain in human beings. 相似文献
20.