Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats

Shannon, Harlan E.; Eberle, Elizabeth L.; Peters, Steven

doi:10.1016/j.neuropharm.2005.01.013

Cited by 76 publications

(42 citation statements)

References 49 publications

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“…had produced analgesic effect alone or in combination with opioid and pretreatment with local diclofenac, 25-200mg/paw in formalin test in the past. 16,17 Our study reveals that Gabapentin inhibits late phase of formalin test. The second or the late phase of formalin test represents the central sensitization to pain which plays a key role in perpetuation of pain, especially in neuropathic pain syndromes even after the painful stimulus has been withdrawn.…”

Section: Discussionmentioning

confidence: 69%

Antinociceptive evaluation of conventional anticonvulsant with conventional analgesics on pain model of albino rats and mice

Agarwal¹,

Kansal²

2018

Int J Res Med Sci

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Background: Pain is one of the most common presentations of any disorder and needs immediate and appropriate attention of the treating physician. As pain syndrome involves a variety of etiopathogenesis and temporal domains, management of pain as such requires consideration of many factors that may dictate appropriate therapeutic management. Carabmazepine is an established drug for trigeminal neuralgia while Gabapentin has been tried in postoperative pain but its effectiveness per se and when compared to conventional analgesics needs to be evaluated.Methods: The present study was planned to study the analgesic effects of Gabapentin in various pain models like writhing and formalin test and to compare it with conventional analgesics like Diclofenac sodium and Tramadol in various acute pain models.Results: This study has been carried out in department of Pharmacology, HIMS, Dehradun, for evaluation of Gabapentin for its antinociceptive effect in rats and mice. In the writhing test, a reduction in number of writhes, though insignificant, was found in the Gabapentin pre-treatment group. However, in the first phase of Formalin test which is characterized by licking and biting, Gabapentin produced no significant effect in comparison to control values. In the second phase of leg raising (LR), all three drugs, i.e. Gabapentin and the two positive controls i.e. diclofenac and tramadol produced significant decrease (p< 0.05) in episodes when compared to the control group.Conclusions: Hence the result conclude that Gabapentin could be an effective analgesic drug in visceral and chronic pain in humans but not in acute pain as first phase of formalin test is model of acute and second phase denote chronic pain while writhing test is a model of visceral pain.

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Section: Discussionmentioning

confidence: 69%

Antinociceptive evaluation of conventional anticonvulsant with conventional analgesics on pain model of albino rats and mice

Agarwal¹,

Kansal²

2018

Int J Res Med Sci

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“…In this study, we have demonstrated that single administration of LTG does not induce apoptotic neurodegeneration in the neonatal rats when administered alone in doses at or above those effective for preventing seizures in a variety of rodent models (Dalby and Nielsen, 1997;Yamashita et al, 2004;Shannon et al, 2005) and equivalent to doses at or above the therapeutic range in humans (GlaxoSmithKline, 2006). Although higher doses of LTG (i.e., 50 and 100 mg/kg) caused widespread neuronal cell death, these doses are not likely to be used therapeutically.…”

Section: Discussionmentioning

confidence: 85%

Effects of Lamotrigine Alone and in Combination with MK-801, Phenobarbital, or Phenytoin on Cell Death in the Neonatal Rat Brain

Katz

Kim²,

Gale³

et al. 2007

J Pharmacol Exp Ther

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The neonatal rat brain is vulnerable to neuronal apoptosis induced by antiepileptic drugs (AEDs), especially when given in combination. This study evaluated lamotrigine alone or in combination with phenobarbital, phenytoin, or the glutamate antagonist (ϩ)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) for a proapoptotic action in the developing rat brain. Cell death was assessed in brain regions (striatum, thalamus, and cortical areas) of rat pups (postnatal day 8) by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, 24 h after acute drug treatment. Lamotrigine alone did not increase neuronal apoptosis when given in doses up to 50 mg/kg; a significant increase in cell death occurred after 100 mg/kg. Combination of 20 mg/kg lamotrigine with 0.5 mg/kg MK-801 or 75 mg/kg phenobarbital resulted in a significant increase in TUNEL-positive cells, compared with MK-801 or phenobarbital treatment alone. A similar enhancement of phenytoininduced cell death occurred after 30 mg/kg lamotrigine. In contrast, 20 mg/kg lamotrigine significantly attenuated phenytoininduced cell death. Lamotrigine at 10 mg/kg was without effect on apoptosis induced by phenytoin. Although the functional and clinical implications of AED-induced developmental neuronal apoptosis remain to be elucidated, our finding that lamotrigine alone is devoid of this effect makes this drug attractive as monotherapy for the treatment of women during pregnancy, and for preterm or neonatal infants. However, because AEDs are often introduced as add-on medication, careful selection of drug combinations and doses may be required to avoid developmental neurotoxicity when lamotrigine is used in polytherapy.

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“…39 Of relevance to this review, the antinociceptive effects of several anticonvulsants have been evaluated in the rodent formalin pain model (Table I). While both phases 1 and 2 formalin-induced nociception were shown to be reduced by ethosuximide 40,41 and vigabatrin, 42 only phase 2 was reduced by carbamazepine, 43 gabapentin, 44 lamotrigine, 45 oxcarbazepine 46 and pregabalin. 44 Equivocal results were reported for tiagabine 41,45 and valproic acid, 41,47 possibly due to species differences.…”

Section: Preclinical Evidence Of Analgesic Efficacymentioning

confidence: 99%

Review article: The role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective

Gilron

2006

Can J Anesth/J Can Anesth

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Purpose: Anticonvulsant drugs are effective in the treatment of chronic neuropathic pain but were not, until recently, thought to be useful in more acute conditions such as postoperative pain. However, similar to nerve injury, surgical tissue injury is known to produce neuroplastic changes leading to spinal sensitization and the expression of stimulus-evoked hyperalgesia and allodynia. Pharmacological effects of anticonvulsant drugs which may be important in the modulation of these postoperative neural changes include suppression of sodium channel, calcium channel and glutamate receptor activity at peripheral, spinal and supraspinal sites. The purpose of this article is to review preclinical evidence and clinical trial data describing the efficacy and safety of anticonvulsant drugs in the setting of postoperative pain management. Source: A Medline search was performed to retrieve available literature on the basic and clinical pharmacology of anticonvulsant drugs as they pertain to postoperative pain management. Principal findings: Numerous laboratory studies have described analgesic effects of different anticonvulsant drugs in experimental pain models. Furthermore, several recent clinical trials have shown that anticonvulsants may reduce spontaneous and movement-evoked pain, as well as decrease opioid requirements postoperatively. Some early findings suggest further that anticonvulsant drugs may alleviate postoperative anxiety, accelerate postoperative functional recovery and reduce chronic postsurgical pain. Conclusion: Given the incomplete efficacy of currently available non-opioid analgesics, and the identified benefits of opioid sparing, anticonvulsant medications may be useful adjuncts for postoperative analgesia. Further research in this field is warranted. Objectif

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Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats

Cited by 76 publications

References 49 publications

Antinociceptive evaluation of conventional anticonvulsant with conventional analgesics on pain model of albino rats and mice

Antinociceptive evaluation of conventional anticonvulsant with conventional analgesics on pain model of albino rats and mice

Effects of Lamotrigine Alone and in Combination with MK-801, Phenobarbital, or Phenytoin on Cell Death in the Neonatal Rat Brain

Review article: The role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective

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