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Activation of mammalian target of rapamycin mediates rat pain-related responses induced by BmK I, a sodium channel-specific modulator.

Jiang F, Pang XY, Niu QS, Hua LM, Cheng M, Ji YH - Mol Pain (2013)

Bottom Line: In this study, intraplantar injections of BmK I were found to induce the activation of mTOR, p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) in rat L5-L6 spinal neurons.In addition, intrathecal (i.t.) injection of rapamycin - a specific inhibitor of mTOR - was observed to result in the reduction of spontaneous pain responses and the attenuation of unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I.Thus, these results indicate that the mTOR signaling pathway is mobilized in the induction and maintenance of pain-activated hypersensitivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Lab of Neuropharmacology & Neurotoxicology, Shanghai University, 200444 Shanghai, P,R, China. yhji@staff.shu.edu.cn.

ABSTRACT
The mammalian target of rapamycin (mTOR) is known to regulate cell proliferation and growth by controlling protein translation. Recently, it has been shown that mTOR signaling pathway is involved in long-term synaptic plasticity. However, the role of mTOR under different pain conditions is less clear. In this study, the spatiotemporal activation of mTOR that contributes to pain-related behaviors was investigated using a novel animal inflammatory pain model induced by BmK I, a sodium channel-specific modulator purified from scorpion venom. In this study, intraplantar injections of BmK I were found to induce the activation of mTOR, p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) in rat L5-L6 spinal neurons. In the spinal cord, mTOR, p70 S6K and 4E-BP1 were observed to be activated in the ipsilateral and contralateral regions, peaking at 1-2 h and recovery at 24 h post-intraplantar (i.pl.) BmK I administration. In addition, intrathecal (i.t.) injection of rapamycin - a specific inhibitor of mTOR - was observed to result in the reduction of spontaneous pain responses and the attenuation of unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I. Thus, these results indicate that the mTOR signaling pathway is mobilized in the induction and maintenance of pain-activated hypersensitivity.

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Cellular localization of p-mTOR immunoreactivity in the spinal cord dorsal horn. (A-I) Cell-type-specific immunolabeling of p-mTOR in the ipsilateral dorsal horn at 2 h after intraplantar BmK I injection. Arrows indicate colocalization of the p-mTOR (red) with the respective cell markers (green). (J) Histogram of the cellular distribution of p-mTOR.
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Figure 5: Cellular localization of p-mTOR immunoreactivity in the spinal cord dorsal horn. (A-I) Cell-type-specific immunolabeling of p-mTOR in the ipsilateral dorsal horn at 2 h after intraplantar BmK I injection. Arrows indicate colocalization of the p-mTOR (red) with the respective cell markers (green). (J) Histogram of the cellular distribution of p-mTOR.

Mentions: Confocal microphotography revealed that 74.5 ± 4.2% p-mTOR immunostaining positive profiles were co-localized with the neuronal marker NeuN in the dorsal horn (Figure 5D-F). p-mTOR could be detected in only 9.8 ± 1.2% GFAP-positive astrocytes (Figure 5A-C) and 2.2 ± 0.7% Iba-1-positive microglia (Figure 5G-I).


Activation of mammalian target of rapamycin mediates rat pain-related responses induced by BmK I, a sodium channel-specific modulator.

Jiang F, Pang XY, Niu QS, Hua LM, Cheng M, Ji YH - Mol Pain (2013)

Cellular localization of p-mTOR immunoreactivity in the spinal cord dorsal horn. (A-I) Cell-type-specific immunolabeling of p-mTOR in the ipsilateral dorsal horn at 2 h after intraplantar BmK I injection. Arrows indicate colocalization of the p-mTOR (red) with the respective cell markers (green). (J) Histogram of the cellular distribution of p-mTOR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842742&req=5

Figure 5: Cellular localization of p-mTOR immunoreactivity in the spinal cord dorsal horn. (A-I) Cell-type-specific immunolabeling of p-mTOR in the ipsilateral dorsal horn at 2 h after intraplantar BmK I injection. Arrows indicate colocalization of the p-mTOR (red) with the respective cell markers (green). (J) Histogram of the cellular distribution of p-mTOR.
Mentions: Confocal microphotography revealed that 74.5 ± 4.2% p-mTOR immunostaining positive profiles were co-localized with the neuronal marker NeuN in the dorsal horn (Figure 5D-F). p-mTOR could be detected in only 9.8 ± 1.2% GFAP-positive astrocytes (Figure 5A-C) and 2.2 ± 0.7% Iba-1-positive microglia (Figure 5G-I).

Bottom Line: In this study, intraplantar injections of BmK I were found to induce the activation of mTOR, p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) in rat L5-L6 spinal neurons.In addition, intrathecal (i.t.) injection of rapamycin - a specific inhibitor of mTOR - was observed to result in the reduction of spontaneous pain responses and the attenuation of unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I.Thus, these results indicate that the mTOR signaling pathway is mobilized in the induction and maintenance of pain-activated hypersensitivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Lab of Neuropharmacology & Neurotoxicology, Shanghai University, 200444 Shanghai, P,R, China. yhji@staff.shu.edu.cn.

ABSTRACT
The mammalian target of rapamycin (mTOR) is known to regulate cell proliferation and growth by controlling protein translation. Recently, it has been shown that mTOR signaling pathway is involved in long-term synaptic plasticity. However, the role of mTOR under different pain conditions is less clear. In this study, the spatiotemporal activation of mTOR that contributes to pain-related behaviors was investigated using a novel animal inflammatory pain model induced by BmK I, a sodium channel-specific modulator purified from scorpion venom. In this study, intraplantar injections of BmK I were found to induce the activation of mTOR, p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) in rat L5-L6 spinal neurons. In the spinal cord, mTOR, p70 S6K and 4E-BP1 were observed to be activated in the ipsilateral and contralateral regions, peaking at 1-2 h and recovery at 24 h post-intraplantar (i.pl.) BmK I administration. In addition, intrathecal (i.t.) injection of rapamycin - a specific inhibitor of mTOR - was observed to result in the reduction of spontaneous pain responses and the attenuation of unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I. Thus, these results indicate that the mTOR signaling pathway is mobilized in the induction and maintenance of pain-activated hypersensitivity.

Show MeSH
Related in: MedlinePlus