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Neuroprotective Effect of Anethole Against Neuropathic Pain Induced by Chronic Constriction Injury of the Sciatic Nerve in Mice

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Abstract

Neuropathic pain is an intractable disease with few definitive therapeutic options. Anethole (AN) has been confirmed to possess potent anti-inflammatory and neuroprotective properties, but its effect on neuropathic pain has not been reported. The present study was designed to investigate the antinociceptive effect of AN on chronic constriction injury (CCI)-induced neuropathic pain in mice. AN (125, 250, and 500 mg/kg) and pregabalin (40 mg/kg) were intragastric administered for 8 consecutive days from the 7th day post-surgery. Behavioral parameters were measured on different days, namely, 0, 7, 8, 10, 12, and 14, from CCI operation. Additionally, electrophysiological and histopathological changes were analyzed on the 14th day. Afterward, immunofluorescence and Western blot were utilized to examine the activation of glial cells and the expression of inflammatory cytokines, respectively. AN treatment of CCI mice considerably alleviated hyperalgesia and allodynia, ameliorated abnormal sciatic nerve conduction, and restored injured sciatic nerves in a dose-dependent manner. Furthermore, AN suppressed the activation of glial cells, down-regulated pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL-6, and IL-1β), and up-regulated the anti-inflammatory cytokine (IL-10). These assays first indicated that AN exerted an antinociceptive effect on CCI-induced neuropathic pain, and might be attributed to the anti-inflammatory and neuroprotective activities of AN.

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References

  1. Haanpää M (2010) NeuPSIG guidelines on neuropathic pain assessment. Eur J Neurol 17(8):1010

    Article  PubMed  Google Scholar 

  2. Kerstman E, Ahn S, Battu S, Tariq S, Grabois M (2013) Chap. 15—Neuropathic pain. Elsevier Health Sciences, Philadelphia, pp 175–187

    Google Scholar 

  3. DiBonaventura MD, Sadosky A, Concialdi K, Hopps M, Kudel I, Parsons B, Cappelleri JC, Hlavacek P, Alexander AH, Stacey BR, Markman JD, Farrar JT (2017) The prevalence of probable neuropathic pain in the US: results from a multimodal general-population health survey. J Pain Res 10:2525–2538

    Article  PubMed  PubMed Central  Google Scholar 

  4. O’Connor AB (2009) Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy. Pharmacoeconomics 27(2):95–112

    Article  PubMed  Google Scholar 

  5. Gong SS, Li YX, Zhang MT, Du J, Ma PS, Yao WX, Zhou R, Niu Y, Sun T, Yu JQ (2016) Neuroprotective effect of matrine in mouse model of vincristine-induced neuropathic pain. Neurochem Res 41(11):1–13

    Article  Google Scholar 

  6. Jie W, Jones M, Tanaka M, Selvaraj P, Symes AJ, Cox B, Zhang Y (2018) WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms. J Neuroinflamm 15(1):9

    Article  Google Scholar 

  7. Lee JY, Choi HY, Ju BG, Yune TY (2018) Estrogen alleviates neuropathic pain induced after spinal cord injury by inhibiting microglia and astrocyte activation. Biochim Biophys Acta 1864:2472–2480

    Article  CAS  Google Scholar 

  8. Zahner G, Schaper M, Panzer U, Kluger M, Stahl RA, Thaiss F, Schneider A (2009) Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation. Biochem J 422(3):563–570

    Article  CAS  PubMed  Google Scholar 

  9. Montague K, Simeoli R, Valente J, Malcangio M (2018) A novel interaction between CX3CR1 and CCR2 signalling in monocytes constitutes an underlying mechanism for persistent vincristine-induced pain. J Neuroinflamm 15(1):101

    Article  Google Scholar 

  10. Tsuda M, Inoue K (2016) Neuron-microglia interaction by purinergic signaling in neuropathic pain following neurodegeneration. Neuropharmacology 104:76–81

    Article  CAS  PubMed  Google Scholar 

  11. Yang Y, Hu L, Xia Y, Jiang C, Miao C, Yang C, Yuan M, Wang L (2016) Resveratrol suppresses glial activation and alleviates trigeminal neuralgia via activation of AMPK. J Neuroinflamm 13(1):84

    Article  Google Scholar 

  12. Bridges D, Thompson SW, Rice AS (2001) Mechanisms of neuropathic pain. Br J Anaesth 87(1):12–26

    Article  CAS  PubMed  Google Scholar 

  13. Gao YJ, Ji RR (2010) Chemokines, neuronal–glial interactions, and central processing of neuropathic pain. Pharmacol Ther 126(1):56–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Milligan E, Watkins L (2009) Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 10(1):23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Scholz J, Woolf CJ (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10(11):1361

    Article  CAS  PubMed  Google Scholar 

  16. Tao L, Ding Q, Gao C, Sun X (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 

  17. Eliav E, Benoliel R, Herzberg U, Kalladka M, Tal M (2009) The role of IL-6 and IL-1beta in painful perineural inflammatory neuritis. Brain Behav Immun 23(4):474–484

    Article  CAS  PubMed  Google Scholar 

  18. 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 

  19. Campana WM (2007) Schwann cells: activated peripheral glia and their role in neuropathic pain. Brain Behav Immun 21(5):522–527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Milligan ED, Langer SJ, Sloane EM, He L, Wieselerfrank J, O’Connor K, Martin D, Forsayeth JR, Maier SF, Johnson K (2015) Controlling pathological pain by adenovirally driven spinal production of the anti-inflammatory cytokine, interleukin-10. Eur J Neurosci 21(8):2136–2148

    Article  Google Scholar 

  21. Wiffen PJ, Mcquay HJ, Edwards J, Moore RA (2011) Gabapentin for acute and chronic pain. Cochrane Database Syst Rev 3(2):CD006044

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Modaress NV, Asadipour M (2006) Comparison of the effectiveness of fennel and mefenamic acid on pain intensity in dysmenorrhoea. East Mediterr Health J 12 (3–4):423

    Google Scholar 

  24. Javidnia K, Dastgheib L, Mohammadi SS, Nasiri A (2003) Antihirsutism activity of fennel (fruits of Foeniculum vulgare) extract. A double-blind placebo controlled study. Phytomedicine 10(6):455–458

    Article  CAS  PubMed  Google Scholar 

  25. Choi EM, Hwang JK (2004) Antiinflammatory, analgesic and antioxidant activities of the fruit of Foeniculum vulgare. Fitoterapia 75(6):557–565

    Article  PubMed  Google Scholar 

  26. Chainy GB, Manna SK, Chaturvedi MM, Aggarwal BB (2000) Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF-kappaB, AP-1, JNK, MAPKK and apoptosis. Oncogene 19(25):2943–2950

    Article  CAS  PubMed  Google Scholar 

  27. Kang P, Kim KY, Lee HS, Min SS, Seol GH (2013) Anti-inflammatory effects of anethole in lipopolysaccharide-induced acute lung injury in mice. Life Sci 93(24):955–961

    Article  CAS  PubMed  Google Scholar 

  28. Geronikaki AA, Gavalas AM (2006) Antioxidants and inflammatory disease: synthetic and natural antioxidants with anti-inflammatory activity. Comb Chem High Throughput Screen 9(6):425–442

    Article  CAS  PubMed  Google Scholar 

  29. Newberne P, Smith RL, Doull J, Goodman JI, Munro IC, Portoghese PS, Wagner BM, Weil CS, Woods LA, Adams TB (1999) The FEMA GRAS assessment of trans-anethole used as a flavouring substance. Flavour and Extract Manufacturer’s Association. Food Chem Toxicol 37(7):789–811

    Article  CAS  PubMed  Google Scholar 

  30. Abraham SK (2001) Anti-genotoxicity of trans-anethole and eugenol in mice. Food Chem Toxicol 39(5):493–498

    Article  CAS  PubMed  Google Scholar 

  31. Ritter AM, Domiciano TP Jr, Zarpelon VW, Da AC, Barbosa SL, Natali CP, Cuman MR, Bersani-Amado RK CA (2013) Antihypernociceptive activity of anethole in experimental inflammatory pain. Inflammopharmacology 21(2):187–197

    Article  CAS  PubMed  Google Scholar 

  32. Aprotosoaie AC, Costache II, Miron A (2016) Anethole and its role in chronic diseases. Oxyg Transp Tissue XXXIII 929:247–267

    CAS  Google Scholar 

  33. Drukarch B, Schepens E, Stoof JC, Langeveld CH (1997) Anethole dithiolethione prevents oxidative damage in glutathione-depleted astrocytes. Eur J Pharmacol 329(2–3):259

    Article  CAS  PubMed  Google Scholar 

  34. Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33(1):87

    Article  CAS  PubMed  Google Scholar 

  35. Hervera A, Negrete R, Leánez S, Martín-Campos J, Pol O (2010) The role of nitric oxide in the local antiallodynic and antihyperalgesic effects and expression of delta-opioid and cannabinoid-2 receptors during neuropathic pain in mice. J Pharmacol Exp Ther 334(3):887

    Article  CAS  PubMed  Google Scholar 

  36. Darwish IS, Dessouky IS (2015) Does serum Visfatin represent a biochemical marker to an experimental peripheral neuropathic pain in mice. Pharmacology 96(5–6):248–252

    Article  CAS  Google Scholar 

  37. Domiciano TP, Dalalio MM, Silva EL, Ritter AM, Estevão-Silva CF, Ramos FS, Caparroz-Assef SM, Cuman RK, Bersani-Amado CA (2013) Inhibitory effect of anethole in nonimmune acute inflammation. Naunyn-Schmiedeberg’s Arch Pharmacol 386(4):331–338

    Article  CAS  Google Scholar 

  38. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53(1):55–63

    Article  CAS  PubMed  Google Scholar 

  39. Jasmin L, Kohan L, Franssen M, Janni G, Goff JR (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

    Article  CAS  PubMed  Google Scholar 

  40. Hargreaves K, Dubner R, Brown F, Flores C, Joris J (2015) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32(1):77–88

    Article  Google Scholar 

  41. Beyreuther BK, Geis C, Stöhr T, Sommer C (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 

  42. Kayser V, Farré A, Hamon M, Bourgoin S (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 

  43. Ja’Afer FM, Hamdan FB, Mohammed FH (2006) Vincristine-induced neuropathy in rat: electrophysiological and histological study. Exp Brain Res 173(2):334–345

    Article  PubMed  Google Scholar 

  44. Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL (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 

  45. Liu N, Li YX, Gong SS, Du J, Liu G, Jin SJ, Zhao CJ, Niu Y, Sun T, Yu JQ (2016) Antinociceptive effects of gentiopicroside on neuropathic pain induced by chronic constriction injury in mice: a behavioral and electrophysiological study. Can J Physiol Pharmacol 94(7):1–10

    Google Scholar 

  46. Gould HJ, Soignier RD, Cho SR, Hernandez C, Diamond I, Taylor BK, Paul D (2014) Ranolazine attenuates mechanical allodynia associated with demyelination injury. Pain Med 15(10):1771

    Article  PubMed  Google Scholar 

  47. Sudoh Y, Desai SP, Haderer AE, Sudoh S, Gerner P, Anthony DC, De GU, Wang GK (2004) Neurologic and histopathologic evaluation after high-volume intrathecal amitriptyline. Reg Anesth Pain Med 29(5):434–440

    Article  PubMed  Google Scholar 

  48. Xu L, Zhou S, Feng GY, Zhang LP, Zhao DM, Sun Y, Liu Q, Huang F (2012) Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats. Mol Neurobiol 46(2):265–274

    Article  CAS  PubMed  Google Scholar 

  49. Woolf CJ, Mannion RJ (1999) Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 353(9168):1959–1964

    Article  CAS  PubMed  Google Scholar 

  50. Wang ZF, Li Q, Liu SB, Mi WL, Hu S, Zhao J, Tian Y, Mao-Ying QL, Jiang JW, Ma HJ (2014) Aspirin-triggered Lipoxin A4 attenuates mechanical allodynia in association with inhibiting spinal JAK2/STAT3 signaling in neuropathic pain in rats. Neuroscience 273:65–78

    Article  CAS  PubMed  Google Scholar 

  51. Wang B, Liu S, Fan B, Xu X, Chen Y, Lu R, Xu Z, Liu X (2018) PKM2 is involved in neuropathic pain by regulating ERK and STAT3 activation in rat spinal cord. J Headache Pain 19(1):7

    Article  PubMed  PubMed Central  Google Scholar 

  52. Yeesuk K, Huejung P, Taekwan K, Dongeon M, Haejin L (2009) The effects of Ginkgo biloba extract EGb 761 on mechanical and cold allodynia in a rat model of neuropathic pain. Anesth Analgesia 108(6):1958–1963

    Article  Google Scholar 

  53. Zhang MT, Wang B, Jia YN, Liu N, Ma PS, Gong SS, Niu Y, Sun T, Li YX, Yu JQ (2017) Neuroprotective effect of liquiritin against neuropathic pain induced by chronic constriction injury of the sciatic nerve in mice. Biomed Pharmacother 95(1):186–198

    Article  CAS  PubMed  Google Scholar 

  54. Uçeyler N, Kobsar I, Biko L, Ulzheimer J, Levinson SR, Martini R, Sommer C (2006) Heterozygous P0 deficiency protects mice from vincristine-induced polyneuropathy. J Neurosci Res 84(1):37–46

    Article  PubMed  Google Scholar 

  55. Lehning EJ, Jortner BS, Fox JH, Arezzo JC, Kitano T, Lopachin RM (2000) gamma-diketone peripheral neuropathy. I. Quality morphometric analyses of axonal atrophy and swelling. Toxicol Appl Pharmacol 165(2):127–140

    Article  CAS  PubMed  Google Scholar 

  56. Jarahi M, Sheibani V, Safakhah HA, Torkmandi H, Rashidy-Pour A (2014) Effects of progesterone on neuropathic pain responses in an experimental animal model for peripheral neuropathy in the rat: a behavioral and electrophysiological study. Neuroscience 256(1):403–411

    Article  CAS  PubMed  Google Scholar 

  57. Popiolek-Barczyk K, Mika J (2016) Targeting the microglial signaling pathways: new insights in the modulation of neuropathic pain. Curr Med Chem 23(26):2908–2928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rojewska E, Piotrowska A, Popiolekbarczyk K, Mika J (2018) Botulinum toxin type A-A modulator of spinal neuron-glia interactions under neuropathic pain conditions. Toxins 10(4):145

    Article  PubMed Central  Google Scholar 

  59. Moalem G, Tracey DJ (2006) Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev 51(2):240–264

    Article  CAS  PubMed  Google Scholar 

  60. Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji RR, Bean BP, Woolf CJ (2008) Nociceptors are interleukin-1beta sensors. J Neurosci 28(52):14062–14073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Xu YQ, Jin SJ, Liu N, Li YX, Zheng J, Ma L, Du J, Zhou R, Zhao CJ, Niu Y (2014) Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway. Biochem Biophys Res Commun 451(4):568–573

    Article  CAS  PubMed  Google Scholar 

  62. Chen SX, Liao GJ, Yao PW, Wang SK, Li YY, Zeng WA, Liu XG, Zang Y (2018) Calpain-2 regulates TNF-α expression associated with neuropathic pain following motor nerve injury. Neuroscience 376:142–151

    Article  Google Scholar 

  63. Kim SH, Kim DS, Sung YY, Kim HK (2016) Suppression of airway inflammation by Illicium verum and trans-anethole. Planta Med 81(S 01):S1

    Google Scholar 

  64. Kim KY, Lee HS, Seol GH (2017) Anti-inflammatory effects of trans-anethole in a mouse model of chronic obstructive pulmonary disease. Biomed Pharmacother 91:925

    Article  CAS  PubMed  Google Scholar 

  65. Vanderwall AG, Noor S, Sun MS, Sanchez JE, Yang XO, Jantzie LL, Mellios N, Milligan ED (2018) Effects of spinal non-viral interleukin-10 gene therapy formulated with d-mannose in neuropathic interleukin-10 deficient mice: Behavioral characterization, mRNA and protein analysis in pain relevant tissues. Brain Behav Immun 69:91–112

    Article  CAS  PubMed  Google Scholar 

  66. Sawada M, Suzumura A, Hosoya H, Marunouchi T, Nagatsu T (1999) Interleukin-10 inhibits both production of cytokines and expression of cytokine receptors in microglia. J Neurochem 72(4):1466

    Article  CAS  PubMed  Google Scholar 

  67. Navarro A, Saldaña MT, Pérez C, Torrades S, Rejas J (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(1):1–11

    Article  Google Scholar 

  68. Sałat K, Gdulaargasińska J, Malikowska N, Podkowa A, Lipkowska A, Librowski T (2016) Effect of pregabalin on contextual memory deficits and inflammatory state-related protein expression in streptozotocin-induced diabetic mice. Naunyn-Schmiedeberg’s Arch Pharmacol 389(6):613–623

    Article  Google Scholar 

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Acknowledgements

This project was supported by the National Natural Science Foundation of China (Grant No. 81360182), the Key Research and Development Project in Ningxia Hui Autonomous Region (2017BY079) and the “13th Five-Year Plan” Major Science and Technology Project in Ningxia Hui Autonomous Region (2016BZ07). We are indebted to the staff in the Animal Center and the Science and Technology Centre who provided assistances in the study.

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Correspondence to Huanran Tan or Jianqiang Yu.

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All procedures were performed as approved by the Institutional Animal Ethics Committee of Ningxia Medical University. This study complied with the IASP guidelines and ethical regulations on conscious-experimental animals research.

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Wang, B., Zhang, G., Yang, M. et al. Neuroprotective Effect of Anethole Against Neuropathic Pain Induced by Chronic Constriction Injury of the Sciatic Nerve in Mice. Neurochem Res 43, 2404–2422 (2018). https://doi.org/10.1007/s11064-018-2668-7

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