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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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Related in: MedlinePlus

Post-treatment with rapamycin suppressed unilateral thermal hypersensitivity and bilateral mechanical hypersensitivity induced by intraplantar BmK I injection. (A and B) showed the suppressive effects on BmK I-induced the ipsilateral (A) and contralateral (B) mechanical hypersensitivity by different doses of rapamycin post-treatment (20 μM, 200 μM and 2 mM). (C and D) showed that different doses of rapamycin post-treatment (20 μM, 200 μM and 2 mM) suppressed ipsilateral (C) thermal hypersensitivity but did not affect the contralateral basal thermal threshold value (D). **P<0.01, ***P<0.001, compared with relevant control groups treated with DMSO. n=8 for each group.
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Figure 11: Post-treatment with rapamycin suppressed unilateral thermal hypersensitivity and bilateral mechanical hypersensitivity induced by intraplantar BmK I injection. (A and B) showed the suppressive effects on BmK I-induced the ipsilateral (A) and contralateral (B) mechanical hypersensitivity by different doses of rapamycin post-treatment (20 μM, 200 μM and 2 mM). (C and D) showed that different doses of rapamycin post-treatment (20 μM, 200 μM and 2 mM) suppressed ipsilateral (C) thermal hypersensitivity but did not affect the contralateral basal thermal threshold value (D). **P<0.01, ***P<0.001, compared with relevant control groups treated with DMSO. n=8 for each group.

Mentions: Post-treatment with rapamycin was also found to be able to attenuate BmK I-induced hypersensitivity. Bilateral mechanical hypersensitivity and unilateral thermal hypersensitivity could be suppressed by post-treatment with rapamycin (20 μM, 200 μM and 2 mM) significantly (Figure 11A-C, Table 4). Neither pre- nor post-treatment of rapamycin altered the contralateral basal PWTL values (Figure 9H; Figure 11D).


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)

Post-treatment with rapamycin suppressed unilateral thermal hypersensitivity and bilateral mechanical hypersensitivity induced by intraplantar BmK I injection. (A and B) showed the suppressive effects on BmK I-induced the ipsilateral (A) and contralateral (B) mechanical hypersensitivity by different doses of rapamycin post-treatment (20 μM, 200 μM and 2 mM). (C and D) showed that different doses of rapamycin post-treatment (20 μM, 200 μM and 2 mM) suppressed ipsilateral (C) thermal hypersensitivity but did not affect the contralateral basal thermal threshold value (D). **P<0.01, ***P<0.001, compared with relevant control groups treated with DMSO. n=8 for each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 11: Post-treatment with rapamycin suppressed unilateral thermal hypersensitivity and bilateral mechanical hypersensitivity induced by intraplantar BmK I injection. (A and B) showed the suppressive effects on BmK I-induced the ipsilateral (A) and contralateral (B) mechanical hypersensitivity by different doses of rapamycin post-treatment (20 μM, 200 μM and 2 mM). (C and D) showed that different doses of rapamycin post-treatment (20 μM, 200 μM and 2 mM) suppressed ipsilateral (C) thermal hypersensitivity but did not affect the contralateral basal thermal threshold value (D). **P<0.01, ***P<0.001, compared with relevant control groups treated with DMSO. n=8 for each group.
Mentions: Post-treatment with rapamycin was also found to be able to attenuate BmK I-induced hypersensitivity. Bilateral mechanical hypersensitivity and unilateral thermal hypersensitivity could be suppressed by post-treatment with rapamycin (20 μM, 200 μM and 2 mM) significantly (Figure 11A-C, Table 4). Neither pre- nor post-treatment of rapamycin altered the contralateral basal PWTL values (Figure 9H; Figure 11D).

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