Antinociceptive and neuroprotective effects of bromelain in chronic constriction injury-induced neuropathic pain in Wistar rats
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Background: The continuous search for a novel neuropathic pain drug with few or no side effects has been a main focus of researchers for decades. This study investigated the antinociceptive and neuroprotective effects of bromelain in sciatic nerve ligation-induced neuropathic pain in Wistar rats. Methods: Forty-eight Wistar rats randomly divided into eight groups comprised of six animals each were used for this study. Peripheral neuropathy was induced via chronic constriction of the common sciatic nerve. Thermal hyperalgesic and mechanical allodynia were assessed using a hotplate and von Frey filaments, respectively. The functional recovery and structural architecture of the ligated sciatic nerve were evaluated using the sciatic functional index test and a histological examination of the transverse section of the sciatic nerve. The neuroprotective effects of bromelain were investigated in the proximal sciatic nerve tissue after 21 days of treatment. Results: Bromelain significantly (P < 0.05) attenuated both the thermal hyperalgesia and mechanical allodynic indices of neuropathic pain. There were improvements in sciatic function and structural integrity in rats treated with bromelain. These rats showed significant (P < 0.05) increases in sciatic nerve nuclear transcription factors (nuclear factor erythroid-derived-2-related factors-1 [NrF-1] and NrF-2), antioxidant enzymes (superoxide dismutase and glutathione), and reduced membranelipid peroxidation compared with the ligated control group. Conclusions: This study suggest that bromelain mitigated neuropathic pain by enhancing the activities of nuclear transcription factors (NrF-1 and NrF-2) which increases the antioxidant defense system that abolish neuronal stress and structural disorganization.
Abstract
Background: The continuous search for a novel neuropathic pain drug with few or no side effects has been a main focus of researchers for decades. This study investigated the antinociceptive and neuroprotective effects of bromelain in sciatic nerve ligation-induced neuropathic pain in Wistar rats. Methods: Forty-eight Wistar rats randomly divided into eight groups comprised of six animals each were used for this study. Peripheral neuropathy was induced via chronic constriction of the common sciatic nerve. Thermal hyperalgesic and mechanical allodynia were assessed using a hotplate and von Frey filaments, respectively. The functional recovery and structural architecture of the ligated sciatic nerve were evaluated using the sciatic functional index test and a histological examination of the transverse section of the sciatic nerve. The neuroprotective effects of bromelain were investigated in the proximal sciatic nerve tissue after 21 days of treatment. Results: Bromelain significantly (P < 0.05) attenuated both the thermal hyperalgesia and mechanical allodynic indices of neuropathic pain. There were improvements in sciatic function and structural integrity in rats treated with bromelain. These rats showed significant (P < 0.05) increases in sciatic nerve nuclear transcription factors (nuclear factor erythroid-derived-2-related factors-1 [NrF-1] and NrF-2), antioxidant enzymes (superoxide dismutase and glutathione), and reduced membranelipid peroxidation compared with the ligated control group. Conclusions: This study suggest that bromelain mitigated neuropathic pain by enhancing the activities of nuclear transcription factors (NrF-1 and NrF-2) which increases the antioxidant defense system that abolish neuronal stress and structural disorganization.
참고문헌 (31)
- Jensen TS, "Allodynia and hyperalgesia in neuropathic pain : clinical manifestations and mechanisms", Lancet Neurol, 13, pp.924~935 (2014)
- Muthuraman A, "Drug therapy of neuropathic pain : current developments and future perspectives", Curr Drug Targets, 15, pp.210~253 (2014)
- Kanyadhara S, "Ethanolic extract of Aloe vera ameliorates sciatic nerve ligation induced neuropathic pain", Anc Sci Life, 33, pp.208~215 (2014)
- Duggett NA, "Oxidative stress in the development, maintenance and resolution of paclitaxel-induced painful neuropathy", Neuroscience, 333, pp.13~26 (2016)
- ZHANGENJI, "Intrathecal Administration of Mesenchymal Stem Cells Reduces the Reactive Oxygen Species and Pain Behavior in Neuropathic Rats", The Korean Journal of Pain, 27(3), pp.239~245 (2014), 대한통증학회
- Kim HK, "Phenyl N-tert-butylnitrone, a free radical scavenger, reduces mechanical allodynia in chemotherapy-induced neuropathic pain in rats", Anesthesiology, 112, pp.432~439 (2010)
- Negi G, "Oxidative stress and Nrf2 in the pathophysiology of diabetic neuropathy : old perspective with a new angle", Biochem Biophys Res Commun, 408, pp.1~5 (2011)
- Biswas M, "Role of Nrf1 in antioxidant response element-mediated gene expression and beyond", Toxicol Appl Pharmacol, 244, pp.16~20 (2010)
- Li W, "Molecular mechanisms of Nrf2-mediated antioxidant response", Mol Carcinog, 48, pp.91~104 (2009)
- Majid OW, "Perioperative bromelain reduces pain and swelling and improves quality of life measures after mandibular third molar surgery : a randomized, double-blind, placebo-controlled clinical trial", J Oral Maxillofac Surg, 72, pp.1043~1048 (2014)
- Golezar S, "Ananas comosus Effect on perineal pain and wound healing after episiotomy : a randomized double-blind placebo-controlled clinical trial", Iran Red Crescent Med J, 18, pp.e21019~ (2016)
- Sudjarwo SA, "Anti-inflammatory and analgesic effect of bromelain in mice and rats", Univ Med, 24, pp.155~160 (2005)
- Jiang X, "Chronic trans-astaxanthin treatment exerts antihyperalgesic effect and corrects co-morbid depressive like behaviors in mice with chronic pain", Neurosci Lett, 662, pp.36~43 (2018)
- Kilic FS, "Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies", Indian J Med Res, 135, pp.630~635 (2012)
- Zhu YF, "Changes in functional properties of A-type but not C-type sensory neurons in vivo in a rat model of peripheral neuropathy", J Pain Res, 5, pp.175~192 (2012)
- Zhang MT, "Neuroprotective effect of liquiritin against neuropathic pain induced by chronic constriction injury of the sciatic nerve in mice", Biomed Pharmacother, 95, pp.186~198 (2017)
- Bain JR, "Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat", Plast Reconstr Surg, 83, pp.129~138 (1989)
- Hunter FE Jr, "Swelling and lysis of rat liver mitochondria induced by ferrous ions", J Biol Chem, 238, pp.828~835 (1963)
- Gutteridge JM, "Copper-dependent hydroxyl radical damage to ascorbic acid : formation of a thiobarbituric acid-reactive product", FEBS Lett, 137, pp.327~330 (1982)
- Misra HP, "The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase", J Biol Chem, 247, pp.3170~3175 (1972)
- Ellman GL, "Tissue sulfhydryl groups", Arch Biochem Biophys, 82, pp.70~77 (1959)
- Muthuraman A, "Ameliorative effects of Ocimum sanctum in sciatic nerve transection-induced neuropathy in rats", J Ethnopharmacol, 120, pp.56~62 (2008)
- Taraneh Moini Zanjani, "The Attenuation of Pain Behavior and Serum COX-2 Concentration by Curcumin in a Rat Model of Neuropathic Pain", The Korean Journal of Pain, 27(3), pp.246~252 (2014), 대한통증학회
- Ishola IO, "Analgesic and anti-inflammatory effects of the methanol root extracts of some selected Nigerian medicinal plants", Pharm Biol, 52, pp.1208~1216 (2014)
- Owoyele BV, "Analgesic properties of aqueous bark extract of Adansonia digitata in Wistar rats", Biomed Pharmacother, 97, pp.209~212 (2018)
- Shen N, "Application of sciatic functional index in nerve functional assessment", Microsurgery, 16, pp.552~555 (1995)
- Monte-Raso VV, "Is the Sciatic Functional Index always reliable and reproducible?", J Neurosci Methods, 170, pp.255~261 (2008)
- Hassler SN, "Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats", J Neurochem, 131, pp.413~417 (2014)
- Goel R, "Potential contribution of antioxidant mechanism in the defensive effect of lycopene against partial sciatic nerve ligation induced behavioral, biochemical and histopathological modification in wistar rats", Drug Res (Stuttg), 66, pp.633~638 (2016)
- Luo ZD, "Upregulation of dorsal root ganglion(alpha)2(delta)calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats", J Neurosci, 21, pp.1868~1875 (2001)
- 김민준, "The efficacy of combination treatment of gabapentin and electro-acupuncture on paclitaxel-induced neuropathic pain", The Korean Journal of Physiology & Pharmacology, 21(6), pp.657~666 (2017), 대한약리학회