Comparison of the efficacy of carbamazepine, gabapentin and lamotrigine for neuropathic pain in rats

Chogtu, Bharti; Bairy, KL; Smitha, D; Dhar, Supurna; Himabindu, Penuganchiprolu

doi:10.4103/0253-7613.84980

Cited by 18 publications

(7 citation statements)

References 14 publications

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“…Systemic CBZ has been reported to reduce inflammatory hyperalgesia in a dose‐dependent way. Under experimental conditions in rats, CBZ also exhibits antiinflammatory action . Likewise, we noticed a marked inactivation of previously activated microglia in M30 co‐cultures under CBZ treatment; this effect was not seen under the M5 condition.…”

Section: Discussionmentioning

confidence: 48%

Glia and epilepsy: Experimental investigation of antiepileptic drugs in an astroglia/microglia co‐culture model of inflammation

et al. 2013

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SUMMARYPurpose: The contribution of glial cells, mainly astrocytes and microglia, to the pathophysiology of epilepsy is increasingly appreciated. Glia play a pivotal role in the initiation and maintenance of the central nervous system (CNS) immune response and neuronal metabolic and trophic supply. Recent clinical and experimental evidence suggests a direct relationship between epileptic activity and CNS inflammation, which is characterized by accumulation, activation, and proliferation of microglia and astrocytes. Concomitant glia-mediated mechanisms of action of several antiepileptic drugs (AEDs) have been proposed. However, their direct effects on glial cells have been rarely investigated. We aimed to investigate the effect of commonly used AEDs on glial viability, the gap junctional network, the microglial activation, and cytokine expression in an in vitro astroglia/microglia co-culture model. Methods: Primary astrocytic cultures were prepared from brains of postnatal (P0-P2) Wistar rats and co-cultured with a physiologic amount of 5%, as well as 30% microglia in order to mimic inflammatory conditions. Co-cultures were treated with valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHE), and gabapentin (GBT). Viability and proliferation were measured using the tetrazolium (MTT) assay. The microglial activation state was determined by immunocytochemical labeling. The astroglial connexin 43 (Cx43) expression was measured by Western blot analysis. The transforming growth factor-b1 (TGF-b1) and tumor necrosis factor-a (TNF-a) cytokine levels were measured by the quantitative sandwich enzyme immunosorbent assay (ELISA). Key Findings: Astrocytes, co-cultured with 5% microglia (M5 co-cultures), showed a dose-dependent, significant reduction in glial viability after incubation with PHE and CBZ. Furthermore, VPA led to highly significant microglial activation at all doses examined. The antiinflammatory cytokine TGF-b1 release was induced by high doses of GBT and PHE. Astrocytes co-cultured with 30% microglia (M30 co-cultures) revealed a dose-dependent significant reduction in glial viability after incubation with PHE, accompanied by increased TGF-b1 and TNF-a levels. However, CBZ significantly reduced the amount of activated microglial cells and increased the total number of inactivated microglia. Finally, CBZ resulted in reduced viability at all doses examined. Significance: CNS inflammation is characterized by a disturbance of glial cell functions. Strong microglial activation, a typical hallmark of inflammation, was induced by VPA in M5 and continued in M30 co-cultures. With regard to the direct relation between CNS inflammation and seizures, VPA seems to be unsuitable for reducing inflammatory conditions. The reverse effect was achieved after CBZ. We noticed significant microglial inactivation, after incubation of the M30 co-cultures. In conclusion, we suggest that AEDs with antiinflammatory glial features are beneficial for seizures caused by persistent brain inflammation.

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Section: Discussionmentioning

confidence: 48%

Glia and epilepsy: Experimental investigation of antiepileptic drugs in an astroglia/microglia co‐culture model of inflammation

et al. 2013

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“…Analgetic drugs are often ineffective (Chogtu et al, 2011;Dworkin et al, 2010;Kissin, 2010;Teasell et al, 2010;Vranken, 2009). The development of various technologies in physical medicine results from seeking for alternative and complementary, non-pharmacological methods of treatment (Cruccu et al, 2007;Guastella et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The influence of spatial pulsed magnetic field application on neuropathic pain after tibial nerve transection in rat

Szajkowski¹,

Marcol²,

Właszczuk³

et al. 2013

Electromagnetic Biology and Medicine

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The purpose of the study was to examine the influence of the spatial variable magnetic field (induction: 150-300 µT, 80-150 µT, 20-80 µT; frequency 40 Hz) on neuropathic pain after tibial nerve transection. The experiments were carried out on 64 male Wistar C rats. The exposure of animals to magnetic field was performed 1 d/20 min., 5 d/week, for 28 d. Behavioural tests assessing the intensity of allodynia and sensitivity to mechanical and thermal stimuli were conducted 1 d prior to surgery and 3, 7, 14, 21 and 28 d after the surgery. The extent of autotomy was examined. Histological and immunohistochemical analysis was performed. The use of extremely low-frequency magnetic fields of minimal induction values (20-80 µT/40 Hz) decreased pain in rats after nerve transection. The nociceptive sensitivity of healthy rats was not changed following the exposition to the spatial magnetic field of the low frequency. The results of histological and immunohistochemical investigations confirm those findings. Our results indicate that extremely low-frequency magnetic field may be useful in the neuropathic pain therapy.

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“…The effect shown by gabapentin is similar to our earlier study in paclitaxel induced neuropathic pain where gabapentin was effective in mechanical allodynia but did not show a significant response in hot plate withdrawal latency. [24] Lamotrigine acts by stabilizing the slow inactivated conformation of a subtype of Na + channel [25] and modulates Ca ++ and K + currents. [26] Single and repeated injections of lamotrigine were devoid of effects on von Frey filament induced hypersensitivity in trigeminal neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Comparing the efficacy of carbamazepine, gabapentin and lamotrigine in chronic constriction injury model of neuropathic pain in rats

Chogtu

Bairy

Himabindu

et al. 2013

Int J Nutr Pharmacol Neurol Dis

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Context: Anti-epileptics are used in the treatment of neuropathic pain. Newer anti-epileptics with improved safety profile are being used in neuropathic pain. The animal models of neuropathic pain have helped to find newer drugs for this condition. As the efficacy of these drugs is modest, there is always a need to compare the efficacy of newer anti-epileptics with conventional drugs in this condition. Aims: The aim of this study was to compare the efficacy of anti-epileptics in neuropathic pain induced by chronic constriction injury. Settings and Design: It was a randomised, prospective study. Materials and Methods: The rats were divided into four groups. The first three groups were administered each of carbamazepine, gabapentin and lamotrigine respectively and the fourth group acted as control. Assessment was started on day five of surgery by hot plate method and Randall Selitto test. Statistical Analysis Used: Statistical analysis was done by one way analysis of variance followed by posthoc test. Results: In mechanical allodynia rats treated with lamotrigine and gabapentin (P = 0.001) showed a significant increase in mechanical threshold whereas in thermal hyperalgesia, it was the carbamazepine (P = 0.027) which was superior to other two drugs. Conclusions: Lamotrigine and gabapentin are efficacious in mechanical allodynia whereas carbamazepine is superior in thermal hyperalgesia. This shows that effect of drugs vary in different behavioral tests. So, the choice of treatment in different types of neuropathic pain can vary.

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Comparison of the efficacy of carbamazepine, gabapentin and lamotrigine for neuropathic pain in rats

Cited by 18 publications

References 14 publications

Glia and epilepsy: Experimental investigation of antiepileptic drugs in an astroglia/microglia co‐culture model of inflammation

Glia and epilepsy: Experimental investigation of antiepileptic drugs in an astroglia/microglia co‐culture model of inflammation

The influence of spatial pulsed magnetic field application on neuropathic pain after tibial nerve transection in rat

Comparing the efficacy of carbamazepine, gabapentin and lamotrigine in chronic constriction injury model of neuropathic pain in rats

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