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

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.

• Authors: Jun-Nan Wang, Xue-Jun Zhao, Zhi-Hua Liu, Xu-Li Zhao, Tao Sun, Zhi-Jian Fu
• Journal: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society (Eur Spine J) Vol. 26 Issue 7 Pg. 1961-1968 (07 2017) ISSN: 1432-0932 [Electronic] Germany
• PMID: 28283839 (Publication Type: Journal Article)

Chemical References

• 2-(3,4-dimethoxybenzyl)-7-(1-(1-hydroxyethyl)-4-phenylbutyl)-5-methylimidazo(5,1-f)(1,2,4)triazin-4 (3H)-one
• Anti-Inflammatory Agents
• Biomarkers
• Imidazoles
• Triazines
• Cyclic Nucleotide Phosphodiesterases, Type 2

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Biomarkers (metabolism)
• Blotting, Western
• Cyclic Nucleotide Phosphodiesterases, Type 2 (antagonists & inhibitors)
• Enzyme-Linked Immunosorbent Assay
• Hyperalgesia (drug therapy, etiology, metabolism)
• Imidazoles (therapeutic use)
• Injections, Spinal
• Intervertebral Disc Displacement (complications, drug therapy, metabolism)
• Male
• Random Allocation
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Spinal Cord (metabolism)
• Treatment Outcome
• Triazines (therapeutic use)