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Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats

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Abstract

Purpose

Phosphodiesterase inhibitors possess anti-inflammatory properties. In addition, some studies report that phosphodiesterase 2A (PDE2A) are highly expressed in the dorsal horn of the spinal cord. The present study aimed to investigate whether intrathecal administration of Bay 60-7550, a specific PDE2A inhibitor, could alleviate mechanical allodynia in non-compressive lumbar disc herniation (NCLDH) rats.

Methods

Rat NCLDH models by autologous nucleus pulposus implantation to dorsal root ganglion were established. Vehicle or Bay 60-7550 (0.1, 1.0 mg/kg) was injected by intrathecal catheter at day 1 post-operation. The ipsilateral mechanical withdrawal thresholds were analyzed from the day before surgery to day 7 after surgery. At day 7 post-operation, the ipsilateral lumbar (L4–L6) segments of the spinal dorsal horns were removed, and tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) expressions were measured by ELISA. Furthermore, PDE2A mRNA and protein expressions in spinal cord were measured by Real-Time PCR and Western blot.

Results

Intrathecal administration of the PDE2A inhibitor Bay 60-7550, significantly attenuated mechanical allodynia, down-regulated spinal TNF-α, IL-1β and IL-6 over-expressions, increased the expression of spinal cAMP, as well as cGMP in a more remarkable manner, and decreased the spinal PDE2A expression in NCLDH rats in a dose-dependent manner.

Conclusions

Bay 60-7550 alleviated mechanical allodynia and inflammation in NCLDH rats, which might be associated with increased cAMP and especially cGMP increase. Thus, spinal PDE2A inhibition might represent a potential analgesic strategy for radiculopathy treatment in non-compressive lumbar disc herniation.

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Acknowledgements

All authors were involved in drafting or revising this work. This work was written by Junnan Wang. The coauthors made important improvement to the article. Zhijian Fu had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors approve the article to be published and declare no conflicts of interest. This work was supported by the National key clinical specialty on pain department of China, the National Natural Science Foundation of China (81271346) and the Natural Science Foundation of Shandong Province, China (ZR2010HM097).

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    Authors and Affiliations

    1. Department of Pain Management, Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, Shandong, 250021, China

      Jun-Nan Wang, Xue-jun Zhao, Zhi-hua Liu, Xu-li Zhao, Tao Sun & Zhi-jian Fu

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    1. Jun-Nan Wang
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    Correspondence to Zhi-jian Fu.

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    J. Wang and X. Zhao contributed equally to this work.

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    Wang, JN., Zhao, Xj., Liu, Zh. et al. Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats. Eur Spine J 26, 1961–1968 (2017). https://doi.org/10.1007/s00586-017-5023-9

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