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

ABSTRACT: Current nonsurgical treatments of discogenic lumbar radiculopathy are neither effective nor safe. Our prior studies have suggested that hydroxylated fullerene (fullerol) nanomaterial could attenuate proinflammatory cytokine tumor necrosis factor alpha (TNF-?)-induced neuroinflammation and oxidative stress in mouse dorsal root ganglia (DRG) and primary neurons. Here, we aim to investigate the analgesic effect of fullerol in a clinically relevant lumbar radiculopathy mouse model and to understand its underlying molecular mechanism in mouse DRGs and neurons. Surprisingly, single and local application of fullerol solution (1 ?M, 10 ?L) was sufficient to alleviate ipsilateral paw pain sensation in mice up to 2 weeks postsurgery. In addition, microCT data suggested fullerol potentially promoted disc height recovery following injury-induced disc herniation. Alcian blue/picrosirius red staining also suggested that fullerol promoted regeneration of extracellular matrix proteins visualized by the presence of abundant newly formed collagen and proteoglycan in herniated discs. For in vitro DRG culture, fullerol attenuated TNF-?-elicited expression of transient receptor potential cation channel subfamily V member 1 (TRPV-1) and neuropeptides release (substance P and calcitonin gene-related peptide). In addition, fullerol suppressed TNF-?-stimulated increase in intracellular Ca2+ concentrations in primary neurons. Moreover, Western blot analysis in DRG revealed that fullerol's beneficial effects against TNF-? might be mediated through protein kinase B (AKT) and extracellular protein-regulated kinase (ERK) pathways. These TNF-? antagonizing and analgesic effects indicated therapeutic potential of fullerol in treating lumbar radiculopathy, providing solid preclinical evidence toward further translational studies.

SUBMITTER: Xiao L

PROVIDER: S-EPMC6054467 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Xiao Li L Hong Kwangseok K Roberson Charles C Ding Mengmeng M Fernandez Andrew A Shen Francis F Jin Li L Sonkusare Swapnil S Li Xudong X

ACS biomaterials science & engineering 20171207 1

Current nonsurgical treatments of discogenic lumbar radiculopathy are neither effective nor safe. Our prior studies have suggested that hydroxylated fullerene (fullerol) nanomaterial could attenuate proinflammatory cytokine tumor necrosis factor alpha (TNF-α)-induced neuroinflammation and oxidative stress in mouse dorsal root ganglia (DRG) and primary neurons. Here, we aim to investigate the analgesic effect of fullerol in a clinically relevant lumbar radiculopathy mouse model and to understand ...[more]

PMID: 30038959

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Project description:BackgroundPainful lumbar radiculopathy is a neuropathic pain condition, commonly attributed to nerve root inflammation/compression by disc herniation. The present exploratory study searched for associations between pain intensity and inflammatory markers, herniated disc size, infection, psychological factors and pain modulation in patients with confirmed painful lumbar radiculopathy scheduled for spine surgery.MethodsPrior to surgery, 53 patients underwent the following evaluation: pain intensity measured on a 0-10 numeric rating scale (NRS) and the Short-Form McGill Pain Questionnaire; sensory testing (modified DFNS protocol); pain processing including temporal summation and conditioned pain modulation (CPM); neurological examination; psychological assessment including Spielberger's Anxiety Inventory, Pain Sensitivity Questionnaire and the Pain Catastrophizing Scale. Pro-inflammatory cytokine levels (IL-1b, IL-6, IL-8, IL-17, TNFα, IFNg) and microbial infection (ELISA and rt-PCR) in blood and disc samples obtained during surgery. MRI scans assessments for disc herniation size/volume (MSU classification/ three-dimensional volumetric analysis).ResultsComplete data were available from 40 (75%) patients (15 female) aged 44.8 ± 16.3 years. Pain intensity (NRS) positively correlated with pain catastrophizing and CPM (r = 0.437, p = 0.006; r = 0.421, p = 0.007; respectively), but not with disc/blood cytokine levels, bacterial infection or MRI measures. CPM (p = 0.001) and gender (p = 0.029) were associated with average pain intensity (adjusted R2 = 0.443).ConclusionsThis exploratory study suggests that pain catastrophizing, CPM and gender, seem to contribute to pain intensity in patients with painful lumbar radiculopathy. The role of mechanical compression and inflammation in determining the intensity of painful radiculopathy remains obscure.Significance of studyPain catastrophizing, CPM and gender rather than objective measures of inflammation and imaging seem to contribute to pain in patients with painful radiculopathy.

Dataset Information

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

Publications

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

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