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Simvastatin attenuates formalin-induced nociceptive behaviors by inhibiting microglial RhoA and p38 MAPK activation.
J Pain. 2013 Nov; 14(11):1310-9.JP

Abstract

Several recent studies have revealed that statins exert anti-inflammatory effects in addition to their lipid-lowering property in vivo and in vitro. Recently, statins were shown to alleviate pain associated trauma in a neuropathic pain model. The aim of the present study was to investigate the underlying mechanisms of analgesia caused by the lipophilic statin simvastatin in an animal model of formalin-induced pain in the rat. Intrathecal pretreatment with simvastatin significantly attenuated the second phase of the acute nociceptive response to formalin injection, and daily administration of simvastatin for 7 days inhibited the long-term mechanical hyperalgesia caused by formalin injection. Spinal microglial activation (detected by Iba-1 and CD11 b immunohistochemistry and Western blot), and phosphorylated-p38 mitogen-activated protein kinase (detected by immunohistochemistry and Western blot) were significantly inhibited by simvastatin treatment at day 7 after formalin injection. In addition, peripheral formalin injection induced a significant increase in microglial RhoA activation (detected by membrane RhoA translocation ratio using Western blot) in the spinal cord. The spinal RhoA activation in microglia was reversed by simvastatin treatment. These findings suggest that simvastatin attenuates formalin-induced nociceptive behaviors, at least in part, by inhibiting microglial RhoA and p38 mitogen-activated protein kinase activation.

PERSPECTIVE

Our novel findings indicated that simvastatin attenuated formalin-induced nociceptive responses by inhibiting microglial RhoA and p38 mitogen-activated protein kinase activation. Inactivation of RhoA-p38 signaling pathway may be a pharmacologic target for treating microglia-directed central nervous system inflammation and chronic pain conditions.

Authors+Show Affiliations

Center for TMD & Orofacial Pain, Peking University School & Hospital of Stomatology, Beijing, P R China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23900131

Citation

Chen, Xin-Yi, et al. "Simvastatin Attenuates Formalin-induced Nociceptive Behaviors By Inhibiting Microglial RhoA and P38 MAPK Activation." The Journal of Pain : Official Journal of the American Pain Society, vol. 14, no. 11, 2013, pp. 1310-9.
Chen XY, Li K, Light AR, et al. Simvastatin attenuates formalin-induced nociceptive behaviors by inhibiting microglial RhoA and p38 MAPK activation. J Pain. 2013;14(11):1310-9.
Chen, X. Y., Li, K., Light, A. R., & Fu, K. Y. (2013). Simvastatin attenuates formalin-induced nociceptive behaviors by inhibiting microglial RhoA and p38 MAPK activation. The Journal of Pain : Official Journal of the American Pain Society, 14(11), 1310-9. https://doi.org/10.1016/j.jpain.2013.05.011
Chen XY, et al. Simvastatin Attenuates Formalin-induced Nociceptive Behaviors By Inhibiting Microglial RhoA and P38 MAPK Activation. J Pain. 2013;14(11):1310-9. PubMed PMID: 23900131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simvastatin attenuates formalin-induced nociceptive behaviors by inhibiting microglial RhoA and p38 MAPK activation. AU - Chen,Xin-Yi, AU - Li,Kai, AU - Light,Alan R, AU - Fu,Kai-Yuan, Y1 - 2013/07/27/ PY - 2013/02/19/received PY - 2013/05/07/revised PY - 2013/05/26/accepted PY - 2013/8/1/entrez PY - 2013/8/1/pubmed PY - 2014/6/21/medline KW - Formalin pain model KW - RhoA KW - microglia KW - p38 mitogen-activated protein kinase KW - statins SP - 1310 EP - 9 JF - The journal of pain : official journal of the American Pain Society JO - J Pain VL - 14 IS - 11 N2 - UNLABELLED: Several recent studies have revealed that statins exert anti-inflammatory effects in addition to their lipid-lowering property in vivo and in vitro. Recently, statins were shown to alleviate pain associated trauma in a neuropathic pain model. The aim of the present study was to investigate the underlying mechanisms of analgesia caused by the lipophilic statin simvastatin in an animal model of formalin-induced pain in the rat. Intrathecal pretreatment with simvastatin significantly attenuated the second phase of the acute nociceptive response to formalin injection, and daily administration of simvastatin for 7 days inhibited the long-term mechanical hyperalgesia caused by formalin injection. Spinal microglial activation (detected by Iba-1 and CD11 b immunohistochemistry and Western blot), and phosphorylated-p38 mitogen-activated protein kinase (detected by immunohistochemistry and Western blot) were significantly inhibited by simvastatin treatment at day 7 after formalin injection. In addition, peripheral formalin injection induced a significant increase in microglial RhoA activation (detected by membrane RhoA translocation ratio using Western blot) in the spinal cord. The spinal RhoA activation in microglia was reversed by simvastatin treatment. These findings suggest that simvastatin attenuates formalin-induced nociceptive behaviors, at least in part, by inhibiting microglial RhoA and p38 mitogen-activated protein kinase activation. PERSPECTIVE: Our novel findings indicated that simvastatin attenuated formalin-induced nociceptive responses by inhibiting microglial RhoA and p38 mitogen-activated protein kinase activation. Inactivation of RhoA-p38 signaling pathway may be a pharmacologic target for treating microglia-directed central nervous system inflammation and chronic pain conditions. SN - 1528-8447 UR - https://www.unboundmedicine.com/medline/citation/23900131/Simvastatin_attenuates_formalin_induced_nociceptive_behaviors_by_inhibiting_microglial_RhoA_and_p38_MAPK_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1526-5900(13)01073-0 DB - PRIME DP - Unbound Medicine ER -