Nanoparticle fullerol alleviates radiculopathy via NLRP3 inflammasome and neuropeptides

Abstract

The present study aimed to evaluate the analgesic effect of the antioxidant nanoparticle fullerol in a mouse radiculopathy and a dorsal root ganglion (DRG) culture models. Intervertebral disc degeneration causes significant hyperalgesia and nerve inflammation. Pain sensitization and inflammatory reaction were counteracted by fullerol when disc material was bathed in 10 or 100µM of fullerol prior to implantation. Immunohistochemistry showed similar massive IBA1 positive macrophage infiltration surrounding implanted disc material among groups, but IL-1β and IL-6 expression was decreased in fullerol treated group. In the DRG explant culture, after treatment with TNF-α, the expression of IL-1β, NLRP3, and caspase 1 was significantly increased but this was reversed by the addition of fullerol. In addition, fullerol also decreased the expression of substance P and CGRP in the cultured DRGs. Nanoparticle fullerol effectively counteracts pain sensitization and the inflammatory cascade caused by disc degeneration.

Link protein N-terminal peptide and fullerol promote matrix production and decrease degradation enzymes in rabbit annulus cells

“…However, IVD degeneration is a complex process, involving mechanical stress, oxidation, and a combination of inflammatory cytokines, of which IL-1α plays a crucial, albeit incomplete role. Other studies have used an acute annulus-puncture model to create disc degeneration in rabbits but this method is also limited since multiple factors, rather than a single injury, are involved in the induction of disc degeneration in humans (32,33). Future studies investigating the combined effects of LN and fullerol on the whole IVD using an in vivo model are needed.…”

Neuroimmunomodulatory and Neuroprotective Effects of the Flavonoid Apigenin in in vitro Models of Neuroinflammation Associated With Alzheimer’s Disease

“…LPS a component of the gram-negative bacteria cell membrane, is known to be a potent inducer of the inflammatory response via toll-like receptor 4 (Park and Lee, 2013;Xu et al, 2017) and according to Jin et al (2017), the IL-1β is a proinflammatory cytokine that plays a key role in the initiation and development of a complex cellular inflammatory cascade. Excessive IL-1β production in the CNS, mainly by glial cells, is associated with neuroinflammation found in neurodegenerative processes.…”

Hydroxylated Fullerene: A Stellar Nanomedicine to Treat Lumbar Radiculopathy via Antagonizing TNF-α-Induced Ion Channel Activation, Calcium Signaling, and Neuropeptide Production

“…3 Recently, we further revealed that fullerol inhibited disc material implantation-induced neuronal inflammation by regulating the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome activity and suppressing neurotropic peptide release in a nucleus pulposus (NP) implantation mouse model. 4 Additionally, fullerol has been shown to have a neuroprotective effect for both memory and neuronal damage through Ca 2+ signal transduction. 20 However, it is unclear whether and how fullerol possesses a therapeutic effect in a clinically relevant model that recapitulates herniation-caused radicular pain in humans.…”