Low-Concentration Oxygen/Ozone Treatment Attenuated Radiculitis and Mechanical Allodynia via PDE2A-cAMP/cGMP-NF-κB/p65 Signaling in Chronic Radiculitis Rats

BACKGROUND: Oxygen/ozone therapy is a minimally invasive technique for the treatment of radiculitis from lumbar disc herniation. This study aimed at investigating whether intrathecal administration of low-concentration oxygen/ozone could attenuate chronic radiculitis and mechanical allodynia after noncompressive lumbar disc herniation and at elucidating the underlying mechanisms. METHODS: First, we transplanted autologous nucleus pulposus into dorsal root ganglions to establish chronic radiculitis in rats. Then, filtered oxygen or oxygen/ozone (10, 20, or 30 μg/mL) was intrathecally injected on day 1 after surgery. The ipsilateral paw withdrawal thresholds (PWTs) to mechanical stimuli were tested daily with von Frey filaments. The expression of the tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), phosphodiesterase 2A (PDE2A), and nuclear factor- (NF-) κB/p65 in spinal dorsal horns was measured by enzyme-linked immunosorbent assay, polymerase chain reaction, and western blot on day 7 after surgery. RESULTS: Chronic radiculitis was established in rats. Intrathecal administration of 10 μg/mL, 20 μg/mL, or 30 μg/mL oxygen/ozone significantly attenuated the decreased mechanical PWTs, downregulated the overexpression of spinal TNF-α, IL-1β, and IL-6, and increased the expression of cGMP and cAMP in chronic radiculitis rats. In addition, the effects of treatment with 20 μg/mL oxygen/ozone were greater than the effects of the 10 μg/mL or 30 μg/mL doses. Moreover, intrathecal administration of 20 μg/mL oxygen/ozone reversed the increased levels of spinal PDE2A and NF-κB/p65 mRNA and protein expressions in rats with chronic radiculitis. CONCLUSION: Intrathecal administration of low-concentration oxygen/ozone alleviated mechanical allodynia and attenuated radiculitis, likely by a PDE2A-cGMP/cAMP-NF-κB/p65 signaling pathway in chronic radiculitis rats.