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J Neuroinflammation. 2017 Aug 31;14(1):174. doi: 10.1186/s12974-017-0947-x.

Selective suppression of the JNK-MMP2/9 signal pathway by tetramethylpyrazine attenuates neuropathic pain in rats.

Author information

1
Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Han-Zhong Road, Nanjing, 210029, China.
2
Department of Ophthalmology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
3
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, 221000, China.
4
Department of pain, Shandong Qianfoshan Hospital, Shandong, 250014, China.
5
Department of Gynecologic Oncology, Jiangsu Institute of Cancer Research, Jiangsu Cancer Hospital, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, 210009, China.
6
Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Han-Zhong Road, Nanjing, 210029, China. painresearch@njmu.edu.cn.

Abstract

BACKGROUND:

Activated astrocytes release matrix metalloproteinase-2/9 (MMP-2/9) to induce central sensitization and maintain neuropathic pain. However, the mechanisms involved in the activation of MMP-2/9 on astrocytes during pain remain poorly understood. Meanwhile, there is a lack of effective treatment to inhibit the activation of MMP-2/9 on astrocytes. In this study, we aim to investigate the effect of tetramethylpyrazine (TMP), a natural compound with analgesic effects but unknown mechanisms, on MMP-2/9 in neuropathic pain.

METHODS:

The nociception was assessed by measuring the incidence of foot withdrawal in response to mechanical indentation in rats (n = 6). Cell signaling was assayed using western blotting (n = 6) and immunohistochemistry (n = 5). The astrocyte cell line C8-D1A was cultured to investigate the in vitro effects.

RESULTS:

TMP significantly attenuated the maintenance of chronic constrictive injury (CCI)-induced neuropathic pain, inhibited the activation of astrocytes, and decreased the expression of MMP-2/9. Furthermore, our results indicated that TMP could selectively suppress JNK activity but had no notable effects on ERK and p38. Our study also revealed that the effect of TMP may be dependent on the inhibition of TAK1.

CONCLUSIONS:

Inhibition of astrocyte activation in the spinal cord by tetramethylpyrazine may have utility in the treatment of CCI-induced neuroinflammation, and our results further implicate JNK-MMP-2/9 as a novel target for the attenuation of neuropathic pain.

PMID:
28859670
PMCID:
PMC5580313
DOI:
10.1186/s12974-017-0947-x
[Indexed for MEDLINE]
Free PMC Article

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