Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.
BACKGROUND
Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats.


METHODS
The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA).


RESULTS
In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection.


CONCLUSIONS
This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug.
Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
Shukai
S
Sun
Yue
Y
Yin
Xin
X
Yin
Fale
F
Cao
Daoshu
D
Luo
Ting
T
Zhang
Yunqing
Y
Li
Longxing
L
Ni
D045784:Abietanes / Q000494:pharmacology / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000209:etiology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005620:Freund's Adjuvant / Q000633:toxicity; D005727:Ganglia, Spinal / Q000737:chemistry / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008161:Lumbosacral Region; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza; D016037:Single-Blind Method; D013314:Stress, Mechanical; D050916:TRPV Cation Channels / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D045784:Abietanes; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C021751:tanshinone; C028972:dan-shen root extract; D005620:Freund's Adjuvant