Limits...
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.

Show MeSH

Related in: MedlinePlus

200 μM rapamycin inhibited the activation of spinal mTOR, 4E-BP1 and p70 S6K assessed by Western blot. (A) &(F), representative western blots showing levels of p-mTOR, p-4E-BP, p-p70 S6K, total mTOR and β-actin in ipsi- (A) and contralateral (B) side of the spinal cord. (B-E) &(G-J), histograms represent the mean levels with respect to each saline-treated group at 2 h after i.pl. BmK I injection. The data are presented as mean ± S.E.M. of three rats per group. N.s., **p<0.01, ***p<0.001, compared with saline-treated group by One-way ANOVA, followed by Bonferroni's post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3842742&req=5

Figure 9: 200 μM rapamycin inhibited the activation of spinal mTOR, 4E-BP1 and p70 S6K assessed by Western blot. (A) &(F), representative western blots showing levels of p-mTOR, p-4E-BP, p-p70 S6K, total mTOR and β-actin in ipsi- (A) and contralateral (B) side of the spinal cord. (B-E) &(G-J), histograms represent the mean levels with respect to each saline-treated group at 2 h after i.pl. BmK I injection. The data are presented as mean ± S.E.M. of three rats per group. N.s., **p<0.01, ***p<0.001, compared with saline-treated group by One-way ANOVA, followed by Bonferroni's post hoc test.

Mentions: Western blots revealed a significant inhibition of 200 μM rapamycin on mTOR cascades in dorsal spinal cord compared with vehicle and saline (Figure 9). I.t. rapamycin not only decreased the activation of p-mTOR (Figure 9B & G) in both sides, but also p-4E-BP1 (Figure 9C & H) and p-p70 S6K (Figure 9D & I). The total amount of mTOR was not affected by rapamycin.


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)

200 μM rapamycin inhibited the activation of spinal mTOR, 4E-BP1 and p70 S6K assessed by Western blot. (A) &(F), representative western blots showing levels of p-mTOR, p-4E-BP, p-p70 S6K, total mTOR and β-actin in ipsi- (A) and contralateral (B) side of the spinal cord. (B-E) &(G-J), histograms represent the mean levels with respect to each saline-treated group at 2 h after i.pl. BmK I injection. The data are presented as mean ± S.E.M. of three rats per group. N.s., **p<0.01, ***p<0.001, compared with saline-treated group by One-way ANOVA, followed by Bonferroni's post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: 200 μM rapamycin inhibited the activation of spinal mTOR, 4E-BP1 and p70 S6K assessed by Western blot. (A) &(F), representative western blots showing levels of p-mTOR, p-4E-BP, p-p70 S6K, total mTOR and β-actin in ipsi- (A) and contralateral (B) side of the spinal cord. (B-E) &(G-J), histograms represent the mean levels with respect to each saline-treated group at 2 h after i.pl. BmK I injection. The data are presented as mean ± S.E.M. of three rats per group. N.s., **p<0.01, ***p<0.001, compared with saline-treated group by One-way ANOVA, followed by Bonferroni's post hoc test.
Mentions: Western blots revealed a significant inhibition of 200 μM rapamycin on mTOR cascades in dorsal spinal cord compared with vehicle and saline (Figure 9). I.t. rapamycin not only decreased the activation of p-mTOR (Figure 9B & G) in both sides, but also p-4E-BP1 (Figure 9C & H) and p-p70 S6K (Figure 9D & I). The total amount of mTOR was not affected by rapamycin.

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