Combination of Diacerhein and Antiepileptic Drugs After Local Peripheral, and Oral Administration in the Rat Formalin Test

Zúñiga-Romero, Ángel; Ponce-Chávez, Martha Karina; Gauthereau-Torres, Marcia Yvette; Ortega-Varela, Luis Fernando

doi:10.1002/ddr.21232

Cited by 7 publications

(4 citation statements)

References 61 publications

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“…Commonly reported adverse effects of topiramate are dizziness, ataxia, and disorientation 36 . However, previous data of our group indicates that topiramate did not alter rota-rod performance at doses employed here 9 . In fact, Shank et al 37 reported the same effect of this drug even in doses higher than 2000 mg/kg.…”

Section: Antinociceptive Effect Of Topiramate and Ketorolac Combinationcontrasting

confidence: 67%

Evaluation of Antinociceptive Effect of the Ketorolac-Topiramate Combination in the Rat Formalin Test

Cervantes-Durán

Sánchez-Serrano

Gauthereau-Torres

et al. 2021

Bulletin of Pharmaceutical Sciences. Assiut

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Combination therapy approaches to manage acute and chronic pain are commonly used. To characterize the interaction between ketorolac and topiramate in the formalin test, female Wistar rats (200-300 g) were submitted to 1% formalin test. Antinociceptive effect was determined by the administration of ketorolac (3, 10, 30 and 100 mg/kg), topiramate (25, 50, 100 and 200 mg/kg) and their combination by oral route; or ketorolac (25, 50, 100 and 200 µg/paw), topiramate (10, 30, 100 and 300 µg/paw) and their combination by local peripheral route. Isobolographic analysis was used in a fixed dose combination (0.5:0.5) to analyze the nature of the interaction of the combination based on the ED 50 of ketorolac (62.8±21.9 mg/kg) and topiramate (24.3±8.5 mg/kg) by oral administration; or the ED 30 of ketorolac (67.0±7.97 µg/paw) and topiramate (391.3±51.7 µg/paw) by local peripheral route. Combination of these two drugs significantly reduced the number of flinches in second phase of the test. Theoretical ED 50 of the oral combination (ED 50 T) was 43.5±11.7 mg/kg. Experimentally, the ED 50 of the combination (ED 50 E) had a significantly lower value: 16.7±4.0 mg/kg; indicating the presence of supra additive effects (interaction index was 0.38). For local peripheral route, ED 30 T was 229.21±64.99 µg/kg. Experimentally, the ED 30 E had a significantly lower value: 62.00±15.72 µg/paw; indicating synergistic effects (interaction index was 0.27). Results show that oral and local peripheral administration of the combination can interact synergistically to reduce inflammatory pain in the rat formalin test.

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Section: Antinociceptive Effect Of Topiramate and Ketorolac Combinationcontrasting

confidence: 67%

Evaluation of Antinociceptive Effect of the Ketorolac-Topiramate Combination in the Rat Formalin Test

Cervantes-Durán

Sánchez-Serrano

Gauthereau-Torres

et al. 2021

Bulletin of Pharmaceutical Sciences. Assiut

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“…In addition to the release of various inflammatory mediators, formalin can also activate TRPA1 directly to elicit pain and inflammation . This test has been successfully used to assess the efficacy of a variety of compounds like morphine, oxyphenylbutazone, acetylsalicylic acid, corticosteroids , diflunisal , diacerhein, carbamazepine, topiramate, and gabapentin . Antagonists targeting TRPA1 ion channels , NMDA receptors , and neurokinin‐1 receptors have also been examined.…”

Section: Models Of Cutaneous Painmentioning

confidence: 99%

Preclinical Assessment of Inflammatory Pain

2015

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While acute inflammation is a natural physiological response to tissue injury or infection, chronic inflammation is maladaptive and engenders a considerable amount of adverse pain. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings to lower neuronal excitation threshold and sensitize afferent firing rate leading to the development of allodynia and hyperalgesia, respectively. Animal models have aided in our understanding of the pathophysiological mechanisms responsible for the generation of chronic inflammatory pain and allowed us to identify and validate numerous analgesic drug candidates. Here we review some of the commonly used models of skin, joint, and gut inflammatory pain along with their relative benefits and limitations. In addition, we describe and discuss several behavioral and electrophysiological approaches used to assess the inflammatory pain in these preclinical models. Despite significant advances having been made in this area, a gap still exists between fundamental research and the implementation of these findings into a clinical setting. As such we need to characterize inherent pathophysiological pathways and develop new endpoints in these animal models to improve their predictive value of human inflammatory diseases in order to design safer and more effective analgesics.

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“…The doses of GBP used in our study (4.6–16.8 μg/kg) are significantly less than the oral dosages (ca. 25 mg/kg) commonly used in animal models of pain . Even at such a low dose, however, GBP could produce antimetastatic effects.…”

Section: Discussionmentioning

confidence: 99%

Gabapentin, an Analgesic Used Against Cancer‐Associated Neuropathic Pain: Effects on Prostate Cancer Progression in an In Vivo Rat Model

Bugan

Karagoz

Altun

et al. 2015

Basic Clin Pharma Tox

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A major problem associated with clinical management of cancer is controlling the accompanying pain, and various analgesics are in common use for this purpose. Recent evidence suggests that some of the targets of analgesics, such as ion channels and receptors, may also be involved in the cancer process, thereby raising the possibility that such use of some analgesics may impact upon cancer itself. The main aim of this study was to determine whether gabapentin, a common adjuvant analgesic in current use against cancer-associated neuropathic pain, would affect tumour development and progression in vivo. The Dunning rat model of prostate cancer was used. Strongly metastatic Mat-LyLu cells were implanted subcutaneously into syngeneic Copenhagen rats which were then treated every other day with 4.6-16.8 lg/kg gabapentin by gavage. Primary tumourigenesis was monitored daily. Lung metastases were counted and measured after killing the rats 21 days later. Gabapentin had no effect on primary tumourigenesis but produced dose-dependent effects on lung metastasis. Whilst 4.6 lg/kg had no effect, 9.1 lg/kg gabapentin decreased the number of lung metastases significantly by 64%. In contrast, 16.8 lg/kg gabapentin promoted metastasis significantly by 112% and showed a strong tendency to shorten mean survival time. It is concluded that gabapentin prescribed to cancer patients against pain could impact upon the cancer process itself.

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Combination of Diacerhein and Antiepileptic Drugs After Local Peripheral, and Oral Administration in the Rat Formalin Test

Cited by 7 publications

References 61 publications

Evaluation of Antinociceptive Effect of the Ketorolac-Topiramate Combination in the Rat Formalin Test

Evaluation of Antinociceptive Effect of the Ketorolac-Topiramate Combination in the Rat Formalin Test

Preclinical Assessment of Inflammatory Pain

Gabapentin, an Analgesic Used Against Cancer‐Associated Neuropathic Pain: Effects on Prostate Cancer Progression in an In Vivo Rat Model

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