Advertisement

Neurochemical Research

, Volume 43, Issue 4, pp 869–877 | Cite as

Analgesic Effect of Methane Rich Saline in a Rat Model of Chronic Inflammatory Pain

  • Shu-Zhuan Zhou
  • Ya-Lan Zhou
  • Feng Ji
  • Hao-Ling Li
  • Hu Lv
  • Yan Zhang
  • Hua Xu
Original Paper
  • 85 Downloads

Abstract

How oxidative stress contributes to neuro-inflammation and chronic pain is documented, and methane is reported to protect against ischemia–reperfusion injury in the nervous system via anti-inflammatory and antioxidant properties. We studied whether methane in the form of methane rich saline (MS) has analgesic effects in a monoarthritis (MA) rat model of chronic inflammatory pain. Single and repeated injections of MS (i.p.) reduced MA-induced mechanical allodynia and multiple methane treatments blocked activation of glial cells, decreased IL-1β and TNF-α production and MMP-2 activity, and upregulated IL-10 expression in the spinal cord on day 10 post-MA. Furthermore, MS reduced infiltrating T cells and expression of IFN-γ and suppressed MA-induced oxidative stress (MDA and 8-OHDG), and increased superoxide dismutase and catalase activity. Thus, MS may offer anti-inflammatory and antioxidant effects to reduce chronic inflammatory pain.

Keywords

Chronic inflammatory pain Oxidative stress T cells Glial cell Neuro-inflammation Methane rich saline 

Notes

Acknowledgements

This study was supported by the Science and Technology Commission of Shanghai Municipality, China (STCSM, 16ZR1400500).

Author Contributions

S-ZZ, YLZ and FJ performed the behavioral tests, western blot, flow cytometry, gelatin zymographic analysis and drafted the manuscript. HLL and HL participated in the oxidative stress assays, immunohistochemistry, ELISA experiments. YZ produced the statistical analysis. HX conceived the study, designed the experiments, wrote the paper. All of the authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they do not have any conflicts of interest.

Supplementary material

11064_2018_2490_MOESM1_ESM.tif (246.4 mb)
Supplementary material 1 (TIF 252364 KB)

References

  1. 1.
    Chen JJ, Dai L, Zhao LX, Zhu X, Cao S, Gao YJ (2015) Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis. Sci Rep 5:10278CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Hui J, Zhang ZJ, Zhang X, Shen Y, Gao YJ (2013) Repetitive hyperbaric oxygen treatment attenuates complete Freund’s adjuvant-induced pain and reduces glia-mediated neuroinflammation in the spinal cord. J Pain 14(7):747–758CrossRefPubMedGoogle Scholar
  3. 3.
    Mi WL, Mao-Ying QL, Wang XW et al (2011) Involvement of spinal neurotrophin-3 in electroacupuncture analgesia and inhibition of spinal glial activation in rat model of monoarthritis. J Pain 12(9):974–984CrossRefPubMedGoogle Scholar
  4. 4.
    Weyerbacher AR, Xu Q, Tamasdan C, Shin SJ, Inturrisi CE (2010) N-Methyl-d-aspartate receptor (NMDAR) independent maintenance of inflammatory pain. Pain 148(2):237–246CrossRefPubMedGoogle Scholar
  5. 5.
    Kular L, Rivat C, Lelongt B et al (2012) NOV/CCN3 attenuates inflammatory pain through regulation of matrix metalloproteinases-2 and -9. J Neuroinflamm 9:36CrossRefGoogle Scholar
  6. 6.
    Zhang L, Berta T, Xu ZZ, Liu T, Park JY, Ji RR (2011) TNF-α contributes to spinal cord synaptic plasticity and inflammatory pain: distinct role of TNF receptor subtypes 1 and 2. Pain 152(2):419–427CrossRefPubMedGoogle Scholar
  7. 7.
    Xiao MM, Zhang YQ, Wang WT et al (2016) Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation. Sci Rep 6:37251CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Yang KY, Bae WS, Kim MJ et al (2013) Participation of the central p38 and ERK1/2 pathways in IL-1β-induced sensitization of nociception in rats. Prog Neuropsychopharmacol Biol Psychiatry 46:98–104CrossRefPubMedGoogle Scholar
  9. 9.
    Zhu MD, Zhao LX, Wang XT, Gao YJ, Zhang ZJ (2014) Ligustilide inhibits microglia-mediated proinflammatory cytokines production and inflammatory pain. Brain Res Bull 109:54–60CrossRefPubMedGoogle Scholar
  10. 10.
    Grace PM, Rolan PE, Hutchinson MR (2011) Peripheral immune contributions to the maintenance of central glial activation underlying neuropathic pain. Brain Behav Immun 25(7):1322–1332CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang X, Wu Z, Hayashi Y, Okada R, Nakanishi H (2014) Peripheral role of cathepsin S in Th1 cell-dependent transition of nerve injury-induced acute pain to a chronic pain state. J Neurosci 34(8):3013–3022CrossRefPubMedGoogle Scholar
  12. 12.
    Keeble JE, Bodkin JV, Liang L et al (2009) Hydrogen peroxide is a novel mediator of inflammatory hyperalgesia, acting via transient receptor potential vanilloid 1-dependent and independent mechanisms. Pain 141(1–2):135–142CrossRefPubMedGoogle Scholar
  13. 13.
    Kallenborn-Gerhardt W, Möser CV, Lorenz JE et al (2017) Rab7-a novel redox target that modulates inflammatory pain processing. Pain 158(7):1354–1365CrossRefPubMedGoogle Scholar
  14. 14.
    Im YB, Jee MK, Choi JI, Cho HT, Kwon OH, Kang SK (2012) Molecular targeting of NOX4 for neuropathic pain after traumatic injury of the spinal cord. Cell Death Dis 3:e426CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Geis C, Geuss E, Sommer C, Schmidt HH, Kleinschnitz C (2017) NOX4 is an early initiator of neuropathic pain. Exp Neurol 288:94–103CrossRefPubMedGoogle Scholar
  16. 16.
    Iida T, Yi H, Liu S et al (2016) Spinal CPEB-mtROS-CBP signaling pathway contributes to perineural HIV gp120 with ddC-related neuropathic pain in rats. Exp Neurol 281:17–27CrossRefPubMedGoogle Scholar
  17. 17.
    Ge Y, Wu F, Sun X et al (2014) Intrathecal infusion of hydrogen-rich normal saline attenuates neuropathic pain via inhibition of activation of spinal astrocytes and microglia in rats. PLoS ONE 9(5):e97436CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Schwartz ES, Kim HY, Wang J et al (2009) Persistent pain is dependent on spinal mitochondrial antioxidant levels. J Neurosci 29(1):159–168CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lv H, Chen H, Xu JJ et al (2016) Redox imbalance in the peripheral mechanism underlying the mirror-image neuropathic pain due to chronic compression of dorsal root ganglion. Neurochem Res 41(5):958–964CrossRefPubMedGoogle Scholar
  20. 20.
    Singh AK, Vinayak M (2015) Curcumin attenuates CFA induced thermal hyperalgesia by modulation of antioxidant enzymes and down regulation of TNF-α, IL-1β and IL-6. Neurochem Res 40(3):463–472CrossRefPubMedGoogle Scholar
  21. 21.
    CCF B, Zarpelon AC, Pinho-Ribeiro FA et al. (2017) Tempol, a superoxide dismutase mimetic agent, inhibits superoxide anion-induced inflammatory pain in mice. Biomed Res Int 2017: 9584819Google Scholar
  22. 22.
    Ye Z, Chen O, Zhang R et al (2015) Methane attenuates hepatic ischemia/reperfusion injury in rats through antiapoptotic, anti-inflammatory, and antioxidative actions. Shock 44(2):181–187CrossRefPubMedGoogle Scholar
  23. 23.
    Boros M, Ghyczy M, Érces D et al (2012) The anti-inflammatory effects of methane. Crit Care Med 40(4):1269–1278CrossRefPubMedGoogle Scholar
  24. 24.
    He R, Wang L, Zhu J et al (2016) Methane-rich saline protects against concanavalin A-induced autoimmune hepatitis in mice through anti-inflammatory and anti-oxidative pathways. Biochem Biophys Res Commun 470(1):22–28CrossRefPubMedGoogle Scholar
  25. 25.
    Zhang X, Li N, Shao H et al (2016) Methane limit LPS-induced NF-κB/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-3β-mediated IL-10 expression. Sci Rep 6:29359CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Wu J, Wang R, Ye Z et al (2015) Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model. Biochem Biophys Res Commun 466(2):155–161CrossRefPubMedGoogle Scholar
  27. 27.
    Fan DF, Hu HJ, Sun Q et al (2016) Neuroprotective effects of exogenous methane in a rat model of acute carbon monoxide poisoning. Brain Res 1633:62–72CrossRefPubMedGoogle Scholar
  28. 28.
    Wang L, Yao Y, He R et al (2017) Methane ameliorates spinal cord ischemia-reperfusion injury in rats: antioxidant, anti-inflammatory and anti-apoptotic activity mediated by Nrf2 activation. Free Radic Biol Med 103:69–86CrossRefPubMedGoogle Scholar
  29. 29.
    Zhang J, Su YM, Li D et al (2014) TNF-α-mediated JNK activation in the dorsal root ganglion neurons contributes to Bortezomib-induced peripheral neuropathy. Brain Behav Immun 38:185–191CrossRefPubMedGoogle Scholar
  30. 30.
    Chen O, Ye Z, Cao Z et al (2016) Methane attenuates myocardial ischemia injury in rats through anti-oxidative, anti-apoptotic and anti-inflammatory actions. Free Radic Biol Med 90:1–11CrossRefPubMedGoogle Scholar
  31. 31.
    Ji RR, Chamessian A, Zhang YQ (2016) Pain regulation by non-neuronal cells and inflammation. Science 354(6312):572–577CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Zhang ZJ, Jiang BC, Gao YJ (2017) Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain. Cell Mol Life Sci 74(18):3275–3291CrossRefPubMedGoogle Scholar
  33. 33.
    Hua XY, Svensson CI, Matsui T, Fitzsimmons B, Yaksh TL, Webb M (2005) Intrathecal minocycline attenuates peripheral inflammation-induced hyperalgesia by inhibiting p38 MAPK in spinal microglia. Eur J Neurosci 22(10):2431–2440CrossRefPubMedGoogle Scholar
  34. 34.
    Liabakk NB, Talbot I, Smith RA, Wilkinson K, Balkwill F (1996) Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res 56(1):190–196PubMedGoogle Scholar
  35. 35.
    Kawasaki Y, Xu ZZ, Wang X et al (2008) Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med 14(3):331–336CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lee JY, Lee HE, Kang SR, Choi HY, Ryu JH, Yune TY (2014) Fluoxetine inhibits transient global ischemia-induced hippocampal neuronal death and memory impairment by preventing blood–brain barrier disruption. Neuropharmacology 79:161–171CrossRefPubMedGoogle Scholar
  37. 37.
    Costigan M, Moss A, Latremoliere A et al (2009) T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J Neurosci 29(46):14415–14422CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Liu XJ, Zhang Y, Liu T et al (2014) Nociceptive neurons regulate innate and adaptive immunity and neuropathic pain through MyD88 adapter. Cell Res 24(11):1374–1377CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Smith JR, Galie PA, Slochower DR, Weisshaar CL, Janmey PA, Winkelstein BA (2016) Salmon-derived thrombin inhibits development of chronic pain through an endothelial barrier protective mechanism dependent on APC. Biomaterials 80:96–105CrossRefPubMedGoogle Scholar
  40. 40.
    Kim RY, Hoffman AS, Itoh N et al (2014) Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis. J Neuroimmunol 274(1–2):53–61CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Hassler SN, Johnson KM, Hulsebosch CE (2014) 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(4):413–417CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of AnesthesiologyChanghai Hospital, The Second Military Medical UniversityShanghaiChina
  2. 2.Department of Anesthesiology188 Hospital of PLAChaozhouChina
  3. 3.Department of Anesthesiology, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  4. 4.Department of AnesthesiologyThe First Affiliated Hospital of Zhejiang UniversityHangzhouChina
  5. 5.Department of AnesthesiologyFudan University Shanghai Cancer CenterShanghaiChina

Personalised recommendations