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

Abstract

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.

[Retracted] Effects of Ozone on Hippocampus BDNF and Fos Expressions in Rats with Chronic Compression of Dorsal Root Ganglia

“…In this preliminary study found that 20 μg/ml of O 3 did not affect the survival of spinal cord cells, whereas ozone concentrations of 30 to 100 μg/ml have been shown to be concentration-dependently neurotoxic to spinal cord neurons [17]. Intrathecal injection of ozone at concentrations of 10, 20, or 30 μg/mL has been shown to significantly reduce mechanical PWT; ozone concentration of 20 μg/ml could not induce nerve damage and was reported to have an anti-inflammatory effect [18]. Ozone at high concentrations Figure 3: BDNF was mainly expressed in the cytoplasm and on the membrane of hippocampal cells in each group, as represented by brown staining.…”

Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine

“…Given that EA could influence multiple signaling pathways, including β-endorphins ( Han, 2003 ), cannabinoid CB2 receptors, and adenosine A1 receptor ( Goldman et al, 2010 ), the 5-HT 7 R-associated PKA and ERK 1 / 2 phosphorylation through Gαs-cAMP signaling is likely only one of the key factors involved in EA’s maintenance of antihyperalgesic effects. Moreover, cAMP interacts with several other proteins in addition to PKA and ERK 1 / 2 , including ROS ( Gu et al, 2018 ), NF-κB ( Wang J. et al, 2018 ), and AKAP ( Miyano et al, 2019 ), which might also be involved in the maintenance of the antihyperalgesic effects by EA. Next, we will use naloxone to block opioid receptors, or DPCPX to block A1 receptors, so as to exclude the effect of other factors on EA antihyperalgesia, and then confirm the role of 5-HT 7 R.…”

Determining 5HT7R’s involvement in modifying the antihyperalgesic effects of electroacupuncture on rats with recurrent migraine

“…including β-endorphins [73], cannabinoid CB2 receptors [74], and adenosine A1 receptor [75], the 5-HT 7 Rmediated PKA and ERK 1/2 phosphorylation through Gαs-cAMP signaling is likely only one of the key factors involved in EA's maintenance of antihyperalgesic effects. Moreover, cAMP interacts with several other proteins in addition to PKA and ERK 1/2 , including ROS [76], NF-κB [77], and AKAP [78], which might also be involved in the maintenance of the antihyperalgesic effects by EA. Next, we will use naloxone to block opioid receptors, or DPCPX to block A1 receptors, so as to exclude the effect of other factors on EA antihyperalgesia, and then con rm the role of 5-HT 7 R.…”