Procyanidins Attenuate Neuropathic Pain by Suppressing Matrix Metalloproteinase-9/2

Overview

Journal J Neuroinflammation

Publisher Biomed Central

Date 2018 Jun 23

PMID 29929563

Citations 15

Authors

Cailong Pan

Chaoyu Wang

Li Zhang

Ling Song

Yuan Chen

Bingqian Liu

Wen-Tao Liu

Liang Hu

Yinbing Pan

Affiliations

Soon will be listed here.

Abstract

Background: Management of neuropathic pain is a real clinical challenge. Despite intense investigation, the mechanisms of neuropathic pain remain substantially unidentified. Matrix metalloproteinase (MMP)-9 and MMP-2 have been reported to contribute to the development and maintenance of neuropathic pain. Therefore, inhibition of MMP-9/2 may provide a novel therapeutic approach for the treatment of neuropathic pain. In this study, we aim to investigate the effect of procyanidins (PC), clinically used health product, on MMP-9/2 in neuropathic pain.

Methods: The nociception was assessed by measuring the incidence of foot withdrawal in response to mechanical indentation in mice. Cell signaling was assayed using gelatin zymography, western blotting, and immunohistochemistry. The BV2 cells were cultured to investigate the effects of PC on microglia.

Results: Both in vitro and in vivo administration of PC significantly suppresses the activity of MMP-9/2. Oral administration of PC relieves neuropathic pain behaviors induced by chronic constriction sciatic nerve injury (CCI) in mice. Additionally, PC blocks the maturation of interleukin-1β, which is a critical substrate of MMPs, and markedly suppresses CCI-induced MAPK phosphorylation and neuronal and microglia activation, including the reduced phosphorylation of protein kinase C γ and NMDAR1. Furthermore, PC decreases the phosphorylation of p38 mitogen-activated protein kinase and inhibits the translocation of nuclear factor-κB (NF-κB) in microglia.

Conclusions: PC is an effective and safe approach to alleviate neuropathic pain via a powerful inhibition on the activation of MMP-9/2.

Citing Articles

MMP9: Link between neuropathy and colorectal cancer?.

Regalado C, Balogh M Front Mol Biosci. 2024; 11:1451611.

PMID: 39664453 PMC: 11631744. DOI: 10.3389/fmolb.2024.1451611.

Grape seed-derived procyanidins decreases neuropathic pain and nerve regeneration by suppression of toll-like receptor 4-myeloid differentiation factor-88 signaling.

Hu L, An E, Zhu Z, Cai Y, Ye X, Zhou H Mol Pain. 2024; 20:17448069241256466.

PMID: 38716504 PMC: 11110500. DOI: 10.1177/17448069241256466.

SPOCK2 modulates neuropathic pain by interacting with MT1-MMP to regulate astrocytic MMP-2 activation in rats with chronic constriction injury.

Wang C, Xu Y, Xu M, Sun C, Zhang X, Tao X J Neuroinflammation. 2024; 21(1):57.

PMID: 38388415 PMC: 10885439. DOI: 10.1186/s12974-024-03051-5.

Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study.

Li X, Wu Y, Wang H, Li Z, Ding X, Dou C Evid Based Complement Alternat Med. 2023; 2023:3734861.

PMID: 37876856 PMC: 10593550. DOI: 10.1155/2023/3734861.

Developmental Approaches to Chronic Pain: A Narrative Review.

Patel N, Bates C, Patel A Cureus. 2023; 15(9):e45238.

PMID: 37842431 PMC: 10576536. DOI: 10.7759/cureus.45238.

References

Tseng H, Lee I, Lin C, Chi P, Cheng S, Shih R . IL-1β promotes corneal epithelial cell migration by increasing MMP-9 expression through NF-κB- and AP-1-dependent pathways. PLoS One. 2013; 8(3):e57955. PMC: 3591450. DOI: 10.1371/journal.pone.0057955. View

Li J, Lau G, Chen L, Dong S, Lan H, Huang X . Interleukin 17A promotes hepatocellular carcinoma metastasis via NF-kB induced matrix metalloproteinases 2 and 9 expression. PLoS One. 2011; 6(7):e21816. PMC: 3131399. DOI: 10.1371/journal.pone.0021816. View

Malmberg A, Chen C, Tonegawa S, Basbaum A . Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma. Science. 1997; 278(5336):279-83. DOI: 10.1126/science.278.5336.279. View

Zhou R, Yazdi A, Menu P, Tschopp J . A role for mitochondria in NLRP3 inflammasome activation. Nature. 2010; 469(7329):221-5. DOI: 10.1038/nature09663. View

Li J, Xu L, Deng X, Jiang C, Pan C, Chen L . N-acetyl-cysteine attenuates neuropathic pain by suppressing matrix metalloproteinases. Pain. 2016; 157(8):1711-1723. DOI: 10.1097/j.pain.0000000000000575. View

Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P . Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II. Life Sci. 2004; 75(21):2505-13. DOI: 10.1016/j.lfs.2003.10.043. View

Ji R, Berta T, Nedergaard M . Glia and pain: is chronic pain a gliopathy?. Pain. 2013; 154 Suppl 1:S10-S28. PMC: 3858488. DOI: 10.1016/j.pain.2013.06.022. View

Milligan E, Watkins L . Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci. 2008; 10(1):23-36. PMC: 2752436. DOI: 10.1038/nrn2533. View

Monagas M, Khan N, Andres-Lacueva C, Casas R, Urpi-Sarda M, Llorach R . Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Am J Clin Nutr. 2009; 90(5):1144-50. DOI: 10.3945/ajcn.2009.27716. View

10.

Ji R, Xu Z, Gao Y . Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 2014; 13(7):533-48. PMC: 4228377. DOI: 10.1038/nrd4334. View

11.

Vecil G, LARSEN P, Corley S, Herx L, Besson A, Goodyer C . Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo. J Neurosci Res. 2000; 61(2):212-24. DOI: 10.1002/1097-4547(20000715)61:2<212::AID-JNR12>3.0.CO;2-9. View

12.

Costigan M, Scholz J, Woolf C . Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009; 32:1-32. PMC: 2768555. DOI: 10.1146/annurev.neuro.051508.135531. View

13.

Kawasaki Y, Xu Z, Wang X, Park J, Zhuang Z, Tan P . Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med. 2008; 14(3):331-6. PMC: 2279180. DOI: 10.1038/nm1723. View

14.

Basbaum A, Bautista D, Scherrer G, Julius D . Cellular and molecular mechanisms of pain. Cell. 2009; 139(2):267-84. PMC: 2852643. DOI: 10.1016/j.cell.2009.09.028. View

15.

Kim H, Park H, Son K, Chang H, Kang S . Biochemical pharmacology of biflavonoids: implications for anti-inflammatory action. Arch Pharm Res. 2008; 31(3):265-73. DOI: 10.1007/s12272-001-1151-3. View

16.

Jha S, Srivastava S, Brickey W, Iocca H, Toews A, Morrison J . The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J Neurosci. 2010; 30(47):15811-20. PMC: 6633756. DOI: 10.1523/JNEUROSCI.4088-10.2010. View

17.

Ji R, Xu Z, Wang X, Lo E . Matrix metalloprotease regulation of neuropathic pain. Trends Pharmacol Sci. 2009; 30(7):336-40. PMC: 2706286. DOI: 10.1016/j.tips.2009.04.002. View

18.

Simon C, Simon M, Vucelic G, Hicks M, Plinkert P, Koitschev A . The p38 SAPK pathway regulates the expression of the MMP-9 collagenase via AP-1-dependent promoter activation. Exp Cell Res. 2001; 271(2):344-55. DOI: 10.1006/excr.2001.5374. View

19.

Van Wart H, Birkedal-Hansen H . The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci U S A. 1990; 87(14):5578-82. PMC: 54368. DOI: 10.1073/pnas.87.14.5578. View

20.

Liu W, Han Y, Liu Y, Song A, Barnes B, Song X . Spinal matrix metalloproteinase-9 contributes to physical dependence on morphine in mice. J Neurosci. 2010; 30(22):7613-23. PMC: 3842477. DOI: 10.1523/JNEUROSCI.1358-10.2010. View