کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8839081 | 1613222 | 2017 | 32 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chemokine CCL8 and its receptor CCR5 in the spinal cord are involved in visceral pain induced by experimental colitis in mice
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Visceral hypersensitivity induced by inï¬ammatory bowel disease (IBD) is a clinical challenge since the underlying mechanisms remain elusive. Chemokines and their receptors have been suggested to modulate inï¬ammatory pain and neuropathic pain. However, the exact chemokines involved in visceral pain remain to be determined. Here, we investigated the effects of spinal chemokine CCL8 and its major receptor CCR5 on the development of visceral hyperalgesia. We showed that intracolonic injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice produced significant colonic inflammation and visceral hypersensitivity to colorectal distension. Moreover, the mRNA and protein expression of CCL8 and CCR5 in the lumbosacral spinal cord were significantly upregulated. Both of CCL8 and CCR5 were expressed in spinal neurons. Furthermore, TNBS induced the activation of extracellular signal-regulated kinase (ERK) in the spinal cord. The induction of visceral pain by TNBS was attenuated by injection of ERK upstream kinase (MEK) inhibitor PD98059. Finally, intrathecal CCL8 neutralizing antibody or CCR5 antagonist DAPTA dose-dependently suppressed TNBS-evoked visceral hyperalgesia and spinal ERK activation. Taken together, these data demonstrated that CCL8 and CCR5, expressed and upregulated in spinal neurons after colonic inflammation, are involved in the maintenance of visceral hyperalgesia via the activation of spinal ERK. Targeting CCL8/CCR5/ERK pathway in the spinal cord might provide a novel treatment for the relief of visceral pain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research Bulletin - Volume 135, October 2017, Pages 170-178
Journal: Brain Research Bulletin - Volume 135, October 2017, Pages 170-178
نویسندگان
Ying Lu, Bao-Chun Jiang, De-Li Cao, Lin-Xia Zhao, You-Li Zhang,