Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia, phosphorylation of NMDA receptors, and cytokines expression in the thoracic spinal dorsal horn

BMC Gastroenterology

Wang Wei¹  Zhao Qing-Chuan²  Zhang Xu-Jie²  Liu Zhao-Xu²  Wang Shi-Qi²  Li Shu-Jun²  Feng Xiang-Ying²  Feng Fan²  Feng Quan-Xin² 

[1] Department of Anesthesiology, School of Stomatology, the Fourth Military Medical University, No. 145 West Changle Road, Xi’an, 710032, China;Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, No. 127 West Changle Road, Xi’an, 710032, China

关键词: NMDA Receptor;    Resolvin D1;    Spinal dorsal horn;    Pain;    Chronic pancreatitis;   

Others  :  858327
DOI  :  10.1186/1471-230X-12-148

 received in 2012-05-07, accepted in 2012-10-10,  发布年份 2012

【 摘 要 】

Background

We previously reported that immune activation in the spinal dorsal horn contributes to pain induced by chronic pancreatitis (CP). Targeting immune response in the CNS may provide effective treatments for CP-induced pain. Recent findings demonstrate that resolvin D1 (RvD1) can potently dampen inflammatory pain. We hypothesized that intrathecal injection of RvD1 may inhibit pain of CP.

Methods

Rat CP model was built through intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). All the rats were divided into three groups: TNBS, sham, and naïve controls and were further divided for intrathecal RvD1 administration. Pain behavior of rats was tested with von Frey filaments. Anxiety-like behavior and free locomotor and exploration of rats were evaluated by open field test and elevated plus maze. Pancreatic histology was evaluated with hematoxylin and eosin staining. Phosphorylation of NMDA receptor and expression of inflammatory cytokines were examined with Western blot, real-time RT-PCR and ELISA.

Results

Behavioral study indicated that compared to the vehicle control, RvD1 (100 ng/kg) significantly decreased TNBS-induced mechanical allodynia at 2 h after administration (response frequencies: 49.2 ± 3.7% vs 71.3 ± 6.1%), and this effect was dose-dependent. Neither CP nor RvD1 treatment could affect anxiety-like behavior. CP or RvD1 treatment could not affect free locomotor and exploration of rats. Western blot analysis showed that compared with that of naïve group, phosphorylated NR1 (pNR1) and pNR2B in TNBS rats were significantly increased in the spinal cord (pNR1: 3.87±0.31 folds of naïve control, pNR2B: 4.17 ± 0.24 folds of naïve control). Compared to vehicle control, 10 ng/kg of RvD1 could significantly block expressions of pNR1 (2.21 ± 0.26 folds of naïve) and pNR2B (3.31 ± 0.34 folds of naïve). Real-time RT-PCR and ELISA data showed that RvD1 (10 ng/kg) but not vehicle could significantly block expressions of TNF-alpha, IL-1beta and IL-6. In addition, RvD1 did not influence pain behavior, NMDA receptor phosphorylation or cytokines production in sham-operated rats.

Conclusions

These data highly suggest that RvD1 could be a novel and effective treatment for CP-induced chronic pain.

【 授权许可】

   
2012 Quan-Xin et al.; licensee BioMed Central Ltd.

【 图 表 】

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