Cholecalciferol (Vitamin D3) Reduces Rat Neuropathic Pain by Modulating Opioid Signaling

Poisbeau, Pierrick; Aouad, Maya; Gazzo, Géraldine; Lacaud, Adrien; Kemmel, Véronique; Landel, Véréna; Lelièvre, Vincent; Féron, François

doi:10.1007/s12035-019-1582-6

Cited by 32 publications

(24 citation statements)

References 85 publications

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“…A neuroprotective effect of vitamin D against methamphetamine-induced dopamine depletion has been demonstrated [51]. Vitamin D3 has been shown to reduce neuropathic pain by modulating opioid signaling in the rodent brain [52]. A low level of vitamin D was observed in methadone maintenance patients [53] and associated with a higher dose opioid for treatment of cancer patients [54].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Opioid Cessation

Cox

Sherva

Lunetta

et al. 2020

JCM

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The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Opioid Cessation

Cox

Sherva

Lunetta

et al. 2020

JCM

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“…The vitamin D receptor has been reported in the amygdala previously [49]. Application of vitamin D has been efficacious in reducing the pain response in rats [50]. It was hypothesized that vitamin D would affect the expression of several opioid genes, leading to pain relief [50].…”

Section: Discussionmentioning

confidence: 99%

“…Application of vitamin D has been efficacious in reducing the pain response in rats [50]. It was hypothesized that vitamin D would affect the expression of several opioid genes, leading to pain relief [50]. Elevation of the vitamin D receptor could trigger an increase in opioid signaling due to neurons being more sensitive to vitamin D. If so, the elevation of the vitamin D receptor at proestrus would lead to an increase in opioid signaling within the amygdala and reduce the pain response during proestrus, as previously observed [40].…”

Section: Discussionmentioning

confidence: 99%

Comparing Gene Expression in the Parabrachial and Amygdala of Diestrus and Proestrus Female Rats after Orofacial Varicella Zoster Injection

Hornung

Pritchard

Kinchington

et al. 2020

IJMS

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The orofacial pain pathway projects to the parabrachial and amygdala, and sex steroids have been shown to affect neuronal activity in these regions. GABA positive cells in the amygdala are influenced by sex steroid metabolites to affect pain, and sex steroids have been shown to alter the expression of genes in the parabrachial, changing neuronal excitability. Mechanisms by which sex steroids affect amygdala and parabrachial signaling are unclear. The expression of genes in the parabrachial and amygdala in diestrus (low estradiol) and proestrus (high estradiol) female rats were evaluated in this study. First, varicella zoster virus was injected into the whisker pad of female rats to induce a pain response. Second, gene expression was quantitated using RNA-seq one week after injection. Genes that had the greatest change in expression and known to function in pain signaling were selected for the quantitation of protein content. Protein expression of four genes in the parabrachial and seven genes in the amygdala were quantitated by ELISA. In the parabrachial, neurexin 3 (Nrnx3) was elevated at proestrus. Nrnx3 has a role in AMPA receptor and GABA signaling. Neuronatin (Nnat) and protein phosphatase, Mg2+/Mn2+ dependent 1E (Ppm1e) were elevated in the parabrachial of diestrus animals both genes having a role in pain signaling. Epoxide hydroxylase (Ephx2) was elevated in the parabrachial at proestrus and the vitamin D receptor (Vdr) was elevated in the amygdala. Ephx2 antagonists and vitamin D have been used to treat neuropathic pain. In conclusion, sex steroids regulate genes in the parabrachial and amygdala that might result in the greater pain response observed during diestrus.

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“…Several previous works illustrated that a high dose of vitamin D supplementation significantly conduces to decrease typical pathogen species and increase the abundance of phylotype of microbes in the gut [ 154 ]. Though numerous studies have reported that vitamin D supplementation prevents neuronal degeneration and improves cold allodynia, mechanical, and heat hyperalgesia in the rat models of NP [ 155 , 156 ], the proven mechanism remains uncertain. Based on these findings, future studies could address more insights on vitamin D and gut microbiota and exploit a novel and promising strategy to treat or prevent NP (Fig.…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy

et al. 2020

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Neuropathic pain (NP) is a sustained and nonreversible condition characterized by long-term devastating physical and psychological damage. Therefore, it is urgent to identify an effective treatment for NP. Unfortunately, the precise pathogenesis of NP has not been elucidated. Currently, the microbiota-gut-brain axis has drawn increasing attention, and the emerging role of gut microbiota is investigated in numerous diseases including NP. Gut microbiota is considered as a pivotal regulator in immune, neural, endocrine, and metabolic signaling pathways, which participates in forming a complex network to affect the development of NP directly or indirectly. In this review, we conclude the current understanding of preclinical and clinical findings regarding the role of gut microbiota in NP and provide a novel therapeutic method for pain relief by medication and dietary interventions.

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Cholecalciferol (Vitamin D3) Reduces Rat Neuropathic Pain by Modulating Opioid Signaling

Cited by 32 publications

References 85 publications

Genome-Wide Association Study of Opioid Cessation

Genome-Wide Association Study of Opioid Cessation

Comparing Gene Expression in the Parabrachial and Amygdala of Diestrus and Proestrus Female Rats after Orofacial Varicella Zoster Injection

Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy

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