title: Tanshinone IIA attenuates neuropathic pain via inhibiting glial activation and immune response.
abstract: Neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia, is a devastating neurological disease that seriously affects patients' quality of life. We have previously shown that tanshinone IIA (TIIA), an important lipophilic component of Danshen, had significant anti-nociceptive effect in somatic and visceral pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA on neuropathic pain and the underlying mechanisms. Therefore, in the present study, by using spinal nerve ligation (SNL) pain model, the antinociceptive and antihyperalgesic effects of TIIA on neuropathic pain were evaluated by intraperitoneal administration in rats. The results indicated that TIIA dose-dependently inhibited SNL-induced mechanical hyperalgesia. As revealed by OX42 levels, TIIA effectively repressed the activation of spinal microglial activation in SNL-induced neuropathic pain. Meanwhile, TIIA also decreased the expressions of inflammatory cytokines TNF-α and IL-1β in the spinal cord. Furthermore, TIIA inhibited oxidative stress by significantly rescuing the superoxide dismutase (SOD) activity and decreasing the malondialdehyde (MDA). Moreover, TIIA depressed SNL-induced MAPKs activation in spinal cord.
  
  
  CONCLUSIONS
  Taken together, our study provides evidence that TIIA inhibited SNL-induced neuropathic pain through depressing microglial activation and immune response by the inhibition of mitogen-activated protein kinases (MAPKs) pathways. Our findings suggest that TIIA might be a promising agent in the treatment of neuropathic pain.
authors.affiliation: The Department of Neurology, The 88th Hospital of PLA, Hongmen Road 6, Taian, 271000, PR China. Electronic address: falecao@163.com.
authors.forename: Fa-Le
authors.initials: FL
authors.lastname: Cao
authors.affiliation: The Department of Pathology, The 88th Hospital of PLA, Hongmen Road 6, Taian, 271000, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
authors.forename: Ke-Rui
authors.initials: KR
authors.lastname: Gong
authors.affiliation: The Department of Neurology, The 88th Hospital of PLA, Hongmen Road 6, Taian, 271000, PR China.
authors.forename: Jin-Tao
authors.initials: JT
authors.lastname: Zhang
mesh_terms: D045784:Abietanes / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D045784:Abietanes; D000700:Analgesics; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C021751:tanshinone
keywords: Glial activation; Immune response; MAPKs; Neuropathic pain; Spinal nerve ligation; Tanshinone IIA