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Neuroprotective Effect of Matrine in Mouse Model of Vincristine-Induced Neuropathic Pain

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Abstract

Chemotherapy drugs such as vincristine (VCR) can cause neuropathic pain, and there is still lack of ideal strategy to treat it. The current study was designed to investigate effect of matrine (MT) on VCR-induced neuropathic pain in animal model. VCR (75 μg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy model in mice. MT (15, 30 and 60 mg/kg, i.p.) and pregabalin (10 mg/kg, i.p.) were administered for 11 consecutive days. Various tests were performed to assess the degree of pain at different days (1, 6, 11, 16, and 21). Von Frey hair, hot plate, cold-plate and paw pressure tests were conducted to assess the degree of mechanical allodynia, thermal hyperalgesia, cold allodynia and mechanical hyperalgesia in the hind paw respectively. The electrophysiological and histopathological changes were also analyzed. Furthermore, tissue malondialdehyde (MDA), total antioxidant capacity (T-AOC),superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total calcium (TCA), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) were measured to investigate possible involvement of MT in inflammation and oxidative stress. Administration of MT attenuated the VCR-induced behavioral alterations as well as electrophysiological and histopathological changes in a dose dependent manner. Further, MT also attenuated the VCR-induced oxidative stress (MDA, T-AOC, GSH-Px, SOD and TCA) and inflammation (MPO, TNF-α, IL-6 and IL-10). Taken together, MT ameliorated VCR-induced painful neuropathy, which might be attributed to neuroprotective effects by subsequent reduction in oxidative stress and anti-inflammatory actions.

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References

  1. Breivik H et al (2006) Survey of chronic pain in Europe: prevalence impact on daily life treatment. Eur J Pain 10(4):287–333

    Article  PubMed  Google Scholar 

  2. Bouhassira D et al (2008) Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 136(3):380–387

    Article  PubMed  Google Scholar 

  3. Woolf CJ, Mannion RJ (1999) Neuropathic pain: a etiology, symptoms, mechanisms, and management. The Lancet 353:1959–1964

    Article  CAS  Google Scholar 

  4. Jensen TS et al (2001) The clinical picture of neuropathic pain. Eur J Pharmacol 429(1–3):1–11

    Article  CAS  PubMed  Google Scholar 

  5. Woolf CJ, Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science 288(5472):1765–1769

    Article  CAS  PubMed  Google Scholar 

  6. Jaggi AS, Singh N (2012) Mechanisms in cancer-chemotherapeutic drugs induced peripheral neuropathy. Toxicology 291(1–3):1–9

    Article  CAS  PubMed  Google Scholar 

  7. Greeshma N et al (2015) Tetrahydrocurcumin exerts protective effect on vincristine induced neuropathy: behavioral, biochemical, neurophysiological and histological evidence. Chem Biol Interact 238:118–128

    Article  CAS  PubMed  Google Scholar 

  8. Dworkin RH et al (2010) Impact of post-herpetic neuralgia and painful diabetic peripheral neuropathy on health care costs. J Pain 11(4):360–368

    Article  PubMed  Google Scholar 

  9. Sałat K et al (2016) Effect of pregabalin on contextual memory deficits and inflammatory state-related protein expression in streptozotocin-induced diabetic mice. Naunyn Schmiedebergs Arch Pharmacol 389(6):613–623

    Article  PubMed  PubMed Central  Google Scholar 

  10. Quintans J et al (2014) Natural products evaluated in neuropathic pain models: a systematic review. Basic Clin Pharmacol Toxicol 114(6):442–450

    Article  CAS  PubMed  Google Scholar 

  11. Zareba G (2009) Phytotherapy for pain relief. Drugs Today 45(6):445–467

    Article  CAS  PubMed  Google Scholar 

  12. Xu YQ et al (2014) Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B. Biochem Biophys Res Commun 451 (4):568–573

    Article  CAS  PubMed  Google Scholar 

  13. Zhao P et al (2015) Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice. Int J Mol Med 36(3):633–644

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang H et al (2013) Protective effects of matrine against progression of high-fructose diet-induced steatohepatitis by enhancing antioxidant and anti-inflammatory defences involving Nrf2 translocation. Food Chem Toxicol 55:70–77

    Article  CAS  PubMed  Google Scholar 

  15. Kim HK et al (2004) Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain 111(1–2):116–124

    Article  CAS  PubMed  Google Scholar 

  16. Novellis V (2007) Role of reactive oxygen species and spinal cord apoptotic genes in the development of neuropathic pain. Pharmacol Res 55(2):158–166

    Article  PubMed  Google Scholar 

  17. Zhao X et al (2015) Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: engagement of antioxidant mechanisms and spinal GABAA receptors. Pharmacol Res 102:286–297

    Article  CAS  PubMed  Google Scholar 

  18. Sircuta C et al (2016) Correlation between the increased release of catecholamines evoked by local anesthetics and their analgesic and adverse effects: role of K+ channel inhibition. Brain Res Bull 124:21–26

    Article  CAS  PubMed  Google Scholar 

  19. Sun T et al (2012) Small interfering RNA-mediated knockdown of NF-κBp65 attenuates neuropathic pain following peripheral nerve injury in rats. Eur J Pharmacol 682(1–3):79–85

    Article  CAS  PubMed  Google Scholar 

  20. Xu M et al (2012) Direct protection of neurons and astrocytes by matrine via inhibition of the NF-κB signaling pathway contributes to neuroprotection against focal cerebral ischemia. Brain Res 1454:48–64

    Article  CAS  PubMed  Google Scholar 

  21. Hu Z et al (1996) Effects of inhibitor of protein kinase C on brain edema formation evoked by experimental cerebral ischemia in gerbils and rats. Yao Xue Xue Bao 31(12):886–890

    CAS  PubMed  Google Scholar 

  22. Yu J et al (2014) Matrine improved the function of heart failure in rats via inhibiting apoptosis and blocking β3 adrenoreceptor/endothelial nitric oxide synthase pathway. Mol Med Rep 10(6):3199–3204

    PubMed  Google Scholar 

  23. Wang H et al (2013) Antinociceptive effects of matrine on neuropathic pain induced by chronic constriction injury. Pharm Biol 51(7):844–850

    Article  CAS  Google Scholar 

  24. Authier N et al (1999) Pain related behaviour during vincristine-induced neuropathy in rats. Neurorep 10(5):965–968

    Article  CAS  Google Scholar 

  25. Pourmohammadi N et al (2012) Lithium attenuates peripheral neuropathy induced by paclitaxel in rats. Basic Clin Pharmacol Toxicol 110(3):231–237

    Article  CAS  PubMed  Google Scholar 

  26. Chaplan SR et al (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53(1):55–63

    Article  CAS  PubMed  Google Scholar 

  27. Jasmin L et al (1998) The cold plate as a test of nociceptive behaviors: description and application to the study of chronic neuropathic and inflammatory pain models. Pain 75(2–3):367–382

    Article  CAS  PubMed  Google Scholar 

  28. Borta A, Schwarting RK (2005) Inhibitory avoidance, pain reactivity, and plus-maze behavior in wistar rats with high versus low rearing activity. Physiol Behav 84(3):387–396

    Article  CAS  PubMed  Google Scholar 

  29. Beyreuther BK et al (2007) Antihyperalgesic efficacy of lacosamide in a rat model for muscle pain induced by TNF. Neuropharmacology 52(5):1312–1317

    Article  CAS  PubMed  Google Scholar 

  30. Kayser V et al (2003) Effects of the novel analgesic, cizolirtine, in a rat model of neuropathic pain. Pain 104(1–2):169–177

    Article  CAS  PubMed  Google Scholar 

  31. Bain JR et al (1989) Functional evaluation of completesciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg 83(1):129–136

    Article  CAS  PubMed  Google Scholar 

  32. De Medinaceli L et al (1982) An index of the functional condition of rats sciatic nerve based on measurements made from walking tracks. Exp Neurol 77(3):634–643

    Article  PubMed  Google Scholar 

  33. Ja’afer F et al (2006) Vincristine-induced neuropathy in rat: electrophysiological and histological study. Exp Brain Res 173(2):334–345

    Article  PubMed  Google Scholar 

  34. Kandhare A et al (2012) Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia 83(4):650–659

    Article  CAS  PubMed  Google Scholar 

  35. Sudoh Y et al (2004) Neurologic and histopathologic evaluation after high volume intrathecal amitriptyline. Reg Anesth Pain Med 29(5):434–440

    Article  PubMed  Google Scholar 

  36. Villani F et al (2008) Serum cytokine in response to chemo-radiotherapy for Hodgkin’s disease. Tumori 94(6):803–808

    CAS  PubMed  Google Scholar 

  37. Lynch JJ et al (2004) Attenuation of mechanical allodynia by clinically utilized drugs in a rat chemotherapy induced neuropathic pain model. Pain 110(1–2):56–63

    Article  CAS  PubMed  Google Scholar 

  38. Diouf B et al (2015) Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia. JAMA 313(8):815–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mei L et al (2015) Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy. Blood Rev 29(4):243–249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Muthuraman A et al (2008) Ameliorative effects of amiloride and pralidoxime in chronic constriction injury and vincristine induced painful neuropathy in rats. Eur J Pharmacol 587(1–3):104–111

    Article  CAS  PubMed  Google Scholar 

  41. Muthuraman A et al (2010) Development of animal model for vasculatic neuropathy: induction by ischemic-reperfusion in the rat femoral artery. J Neurosci Methods 186(2):215–221

    Article  PubMed  Google Scholar 

  42. Shi GB et al (2015) Antinociceptive activity of astragaloside IV in the animal model of chronic constriction injury. Behav Pharmacol 26(5):436–446

    Article  CAS  PubMed  Google Scholar 

  43. Geis C et al (2011) Lacosamide has protective disease modifying properties in experimental vincristine neuropathy. Neuropharmacology 61(4):600–607

    Article  CAS  PubMed  Google Scholar 

  44. Djouhri L, Lawson SN (2004) Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals. Brain Res Rev 46(2):131–145

    Article  PubMed  Google Scholar 

  45. Kiguchi N et al (2008) The critical role of invading peripheral macrophage-derived interleukin-6 in vincristine-induced mechanical allodynia in mice. Eur J Pharmacol 592(1–3):87–92

    Article  CAS  PubMed  Google Scholar 

  46. Milligan ED et al (2005) Controlling pathological pain by adeno virally driven spinal production of the anti-inflammatory cytokine, interleukin-10. Eur J Neurosci 21(8):2136–2148

    Article  PubMed  Google Scholar 

  47. Milligan ED et al (2005) Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10. Mol Pain 1:9

    Article  PubMed  PubMed Central  Google Scholar 

  48. Uceyler N et al (2006) Heterozygous P0 deficiency protects mice from vincristine-induced polyneuropathy. J Neurosci Res 84(1):37–46

    Article  PubMed  Google Scholar 

  49. Muthuraman A, Singh N (2011) Attenuating effect of hydroalcoholic extract of Acorus calamus in vincristine-induced painful neuropathy in rats. J Nat Med 65(3–4):480–487

    Article  CAS  PubMed  Google Scholar 

  50. Young W (1992) Role of calcium in central nervous system injuries. J Neurotrauma 9(suppl 1):S9–S25

    PubMed  Google Scholar 

  51. Muthuraman A, Singh N (2011) Attenuating effect of Acorus calamus extract in chronic constriction injury induced neuropathic pain in rats: an evidence of anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory effects. BMC Complement Altern Med 11:24

    Article  PubMed  PubMed Central  Google Scholar 

  52. Jain V et al (2009) Ameliorative potential of rosiglitazone in tibial and sural nerve transection-induced painful neuropathy in rats. Pharmacol Res 59(6):385–392

    Article  CAS  PubMed  Google Scholar 

  53. Thiagarajan VR et al (2014) Ameliorative effect of Vernonia cinerea in vincristineinduced painful neuropathy in rats. Toxicol Ind Health 30(9):794–805

    Article  PubMed  Google Scholar 

  54. Luo T et al (2015) Matrine inhibits mouse sperm function by reducing sperm [Ca2+] and phospho-ERK1/2. Cell Physiol Biochem 35(1):374–385

    Article  CAS  PubMed  Google Scholar 

  55. Babu A et al (2015) Effect of curcumin in mice model of vincristine-induced neuropathy. Pharm Biol 53(6):838–848

    Article  CAS  PubMed  Google Scholar 

  56. Zimmermann C et al (2004) Antioxidant status in acute stroke patients and patients at stroke risk. Eur Neurol 51(3):157–161

    Article  CAS  PubMed  Google Scholar 

  57. Chen H et al (2011) Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Antioxid Redox Signal 14(8):1505–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Pop-Busui R et al (2002) Dissection of metabolic, vascular, and nerve conduction interrelationships in experimental diabetic neuropathy by cyclo-oxygenase inhibition and acetyl-l-carnitine administration. Diabetes 51(8):2619–2628

    Article  CAS  PubMed  Google Scholar 

  59. Mika J et al (2013) Importance of glial activation in neuropathic pain. Eur J Pharmacol 716(1–3):106–119

    Article  CAS  PubMed  Google Scholar 

  60. Tao L et al (2016) Resveratrol attenuates neuropathic pain through balancing pro-inflammatory and anti-inflammatory cytokines release in mice. Int Immunopharmacol 34:165–172

    Article  CAS  PubMed  Google Scholar 

  61. Sommer C (1999) Animal studies on neuropathic pain: the role of cytokines and cytokine receptors in pathogenesis and therapy. Schmerz 13(5):315–323

    Article  CAS  PubMed  Google Scholar 

  62. Oft M (2014) IL-10: master switch from tumor-promoting inflammation to antitumor immunity. Cancer Immunol Res 2(3):194–199

    Article  CAS  PubMed  Google Scholar 

  63. Sharma R et al (2013) Association of IL-6, IL-10, and TNF-alpha gene polymorphism with malnutrition inflammation syndrome and survival among end stage renal disease patients. J Interferon Cytokine Res 33(7):384–391

    Article  CAS  PubMed  Google Scholar 

  64. Liou CJ et al (2016) Matrine attenuates COX-2 and ICAM-1 expressions in human lung epithelial cells and prevents acute lung injury in LPS-induced mice. Mediat Inflamm 2016:3630485

    Article  Google Scholar 

  65. Navarro A et al (2011) A cost-consequences analysis of the effect of pregabalin in the treatment of peripheral neuropathic pain in routine medical practice in primary care settings. BMC Neurol 11:7

    Article  PubMed  PubMed Central  Google Scholar 

  66. Vasudevan D et al (2014) Efficacy and safety of methylcobalamin, alpha lipoic acid and pregabalin combination versus pregabalin monotherapy in improving pain and nerve conduction velocity in type 2 diabetes associated impaired peripheral neuropathic condition. Ann Indian Acad Neurol 17(1):19–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (Grant No. 81360182), the Ningxia Hui Autonomous Region Science and Technology Support Program (2015BAK45B01), the International Cooperation of Ningxia Scientific Research Projects (2013) and the Key Scientific Research Projects of Ningxia Health Department (20130X). We are indebted to the staff in the Animal Center and the Science and Technology Centre who provided assistance in the study.

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    Authors and Affiliations

    1. Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Xingqing, Ningxia Hui Autonomous Region, Yinchuan, 750004, China

      Shuai-Shuai Gong, Meng-Ting Zhang, Juan Du, Peng-Sheng Ma, Wan-Xia Yao, Ru Zhou & Jian-Qiang Yu

    2. College of Nursing, Ningxia Medical University, Yinchuan, 750004, China

      Yu-Xiang Li

    3. Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China

      Yang Niu

    4. Ningxia Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, 750004, China

      Tao Sun

    5. Ningxia Hui Medicine Modern Engineering Research Center and Collaborative Innovation Center, Ningxia Medical University, Yinchuan, 750004, China

      Jian-Qiang Yu

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    1. Shuai-Shuai Gong
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    The experiments were performed as approved by the Institutional Animal Ethics Committee of Ningxia Medical University. This study complied with the internationally accredited guidelines and ethical regulations on animal research.

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    Shuai-Shuai Gong and Yu-Xiang Li have equally contributed in this work.

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    Gong, SS., Li, YX., Zhang, MT. et al. Neuroprotective Effect of Matrine in Mouse Model of Vincristine-Induced Neuropathic Pain. Neurochem Res 41, 3147–3159 (2016). https://doi.org/10.1007/s11064-016-2040-8

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