Glial cells as target for antidepressants in neuropathic pain

Damo, Elisa; Rieder, Phillip; Çoban, İlknur; Silva, Rangel L.; Kirchhoff, Frank; Simonetti, Manuela; Agarwal, Amit

doi:10.1515/nf-2021-0036

Cited by 3 publications

(5 citation statements)

References 80 publications

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“…This provides a new way of action on the current therapeutic applications of SNRIs, such as Duloxetine in neuropathic pain. SNRIs act by increasing NA availability for signaling in neural pathways and our results suggest that SNRIs-induced analgesia is likely to involve β2-AR signaling in microglia [46,47]. Our observation that β2-AR expression increases in microglia after nerve injury is supportive of this hypothesis.…”

Section: Discussionsupporting

confidence: 77%

Activation of β2-Adrenergic Receptors in Microglia Alleviates Neuropathic Hypersensitivity in Mice

Damo

Agarwal

Simonetti

2023

Cells

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Drugs enhancing the availability of noradrenaline are gaining prominence in the therapy of chronic neuropathic pain. However, underlying mechanisms are not well understood, and research has thus far focused on α2-adrenergic receptors and neuronal excitability. Adrenergic receptors are also expressed on glial cells, but their roles toward antinociception are not well deciphered. This study addresses the contribution of β2-adrenergic receptors (β2-ARs) to the therapeutic modulation of neuropathic pain in mice. We report that selective activation of β2-ARs with Formoterol inhibits pro-inflammatory signaling in microglia ex vivo and nerve injury-induced structural remodeling and functional activation of microglia in vivo. Systemic delivery of Formoterol inhibits behaviors related to neuropathic pain, such as mechanical hypersensitivity, cold allodynia as well as the aversive component of pain, and reverses chronically established neuropathic pain. Using conditional gene targeting for microglia-specific deletion of β2-ARs, we demonstrate that the anti-allodynic effects of Formoterol are primarily mediated by microglia. Although Formoterol also reduces astrogliosis at late stages of neuropathic pain, these functions are unrelated to β2-AR signaling in microglia. Our results underline the value of developing microglial β2-AR agonists for relief from neuropathic pain and clarify mechanistic underpinnings.

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Section: Discussionsupporting

confidence: 77%

Activation of β2-Adrenergic Receptors in Microglia Alleviates Neuropathic Hypersensitivity in Mice

Damo

Agarwal

Simonetti

2023

Cells

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“…SNRIs act by increasing NA availability for signaling in neural pathways our results suggest that SNRIs-induced analgesia is likely to involve β2-AR signaling in microglia [44]. Our observation that β2-AR expression increases in microglia after nerve injury is supportive of this hypothesis.…”

Section: Discussionsupporting

confidence: 73%

Activation of β2-adrenergic receptors in microglia alleviates neuropathic hypersensitivity in mice

Damo

Agarwal

Simonetti

2022

Preprint

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Drugs enhancing the availability of noradrenaline are gaining prominence in the therapy of chronic neuropathic pain. However, underlying mechanisms are not well understood, and research has thus far focused on α2-adrenergic receptors and neuronal excitability. Adrenergic receptors are also expressed on glial cells, but their roles toward antinociception are not well deciphered. This study addresses the contribution of β2-adrenergic receptors (β2-ARs) to the therapeutic modulation of neuropathic pain in mice. We report that selective activation of β2-ARs with Formoterol inhibits pro-inflammatory signaling in microgliaex-vivoand nerve injury-induced structural remodeling and functional activation of microgliain vivo. Systemic delivery of Formoterol inhibits behaviors related to neuropathic pain, such as mechanical hypersensitivity, cold allodynia and the aversive component of pain, and reverses chronically established neuropathic pain. Using conditional gene targeting for microglia-specific deletion of β2-ARs, we demonstrate that the anti-allodynic effects of Formoterol are primarily mediated by microglia. Although Formoterol also reduces astrogliosis at late stages of neuropathic pain, these functions are unrelated to β2-AR signaling in microglia. Our results underline the value of developing microglial β2-AR agonists for relief from neuropathic pain and clarify mechanistic underpinnings.

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“…The description of 2,3-butanediol (5 ′ , 6 ′ ) has already been provided in other laboratory work [30]. For other compounds, it is even the first description of metabolites in the Bacillus genus: methyl iso-stearate (iC18:0) (44), 2-methyl-trans-decalin (5, 6, 8), 2-methyl-cis-decalin (9, 10), 2,6-dimethyldecalin (11), hexylcyclohexane (15), 1,1 ′ -bicyclohexyl (18), 9,17-octadecadienal (45), phenyl-alkanes (26,27,31,33), di-2-propylpentyl-phthalate (59) and the di-2-ethylhexylisophthalate (61), di-t-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione (37), 2,4,6-triisopropylp henol (43), 3,4-dimethylbenzamide (19), octinoxate (50) and dihydroisophorone (3), tertoctyldiphenylamine (48), n-butylbenzenesulfonamide (32), myo-inositol (43 ′ ) and D-pinitol (29 ′ ), and D-galactose oxime (38 ′ ). These metabolites identified for the first time provide a wealth of chemical families for varied applications.…”

Section: Discussionmentioning

confidence: 99%

“…To determine the relevancy of results comparison, significance tests were chosen considering the number of repetitions and the distribution models of the measured variables. Thus, Kruskal-Wallis and Dunn's nonparametric tests were performed with Prism GraphPad 8.2.1 software [50]. The Kruskal-Wallis indicator allows us to determine if there are one or more results deviating from the rank average of all results.…”

Section: Discussionmentioning

confidence: 99%

“…A total of 75 compounds were found to be present in BC extracts and not present in CS2 extracts, as illustrated in Table 3 for analysis without derivatization, and in Table 4 for analysis with derivatization. Some of these identified compounds were strictly found in BC extracts, suggesting a probable production by B. megaterium: 10 fatty acids derivatives (23 ′ , 32 ′ , 34 ′ , 39 ′ , 42 ′ , 44 ′ , 46 ′ , 47 ′ , 36, 44), 5 linear hydrocarbons (4,12,20,24,25), 5 cyclic hydrocarbons with 3 isomers (5,6,8,9,10,11,15,18), 6 amino acids (10 ′ , 12 ′ , 15 ′ , 18 ′ , 20 ′ , 22 ′ ), 2 dipeptides (29, 47), 2 cyclic dipeptides (46, 64), 6 aromatic hydrocarbons (1,16,26,27,31,33), 2 phthalates (59, 61), 2 sugar acids with 1 isomer (9 ′ , 24 ′ , 41 ′ ), 4 polyols with 1 isomer (2 ′ , 4 ′ , 5 ′ , 6 ′ , 21 ′ ), 2 cyclitols (29 ′ , 43 ′ ) and 17 others were identified (3,7,13,14,19,21,23,32,37,43,45,48,50,62, 63, 17 ′ , 38 ′ ). tr indicates integration inferior to 0.1 × 10 6 ; "ND": not detected.…”

Section: Chemical Identification By Gc-msmentioning

confidence: 99%

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Bacillus megaterium: Evaluation of Chemical Nature of Metabolites and Their Antioxidant and Agronomics Properties

Hur,

Saoudi,

Ferhout

et al. 2024

IJMS

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Bacillus megaterium is particularly known for its abundance in soils and its plant growth promotion. To characterize the metabolites excreted by this specie, we performed successive liquid/liquid extractions from bacteria culture medium with different polarity solvents (cyclohexane, dichloromethane, ethyl acetate and butanol) to separate the metabolites in different polarity groups. The extracts were characterized regarding their total phenolic content, the amount of reducing sugar, the concentration of primary amines and proteins, their chromatographic profile by HPLC-DAD-ELSD and their chemical identification by GC-MS. Among the 75 compounds which are produced by the bacteria, 19 identifications were for the first time found as metabolites of B. megaterium and 23 were described for the first time as metabolites in Bacillus genus. The different extracts containing B. megaterium metabolites showed interesting agronomic activity, with a global inhibition of seed germination rates of soya, sunflower, corn and ray grass, but not of corn, compared to culture medium alone. Our results suggest that B. megaterium can produce various metabolites, like butanediol, cyclic dipeptides, fatty acids, and hydrocarbons, with diverse effects and sometimes with opposite effects in order to modulate its response to plant growth and adapt to various environmental effects. These findings provide new insight into bioactive properties of this species for therapeutic uses on plants.

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Glial cells as target for antidepressants in neuropathic pain

Cited by 3 publications

References 80 publications

Activation of β2-Adrenergic Receptors in Microglia Alleviates Neuropathic Hypersensitivity in Mice

Activation of β2-Adrenergic Receptors in Microglia Alleviates Neuropathic Hypersensitivity in Mice

Activation of β2-adrenergic receptors in microglia alleviates neuropathic hypersensitivity in mice

Bacillus megaterium: Evaluation of Chemical Nature of Metabolites and Their Antioxidant and Agronomics Properties

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