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. 2013 Oct 16;30(1):21–32. doi: 10.1007/s12264-013-1377-0

Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator

Feng Jiang 1, Li-Ming Hua 2, Yun-Lu Jiao 2, Pin Ye 2, Jin Fu 2, Zhi-Jun Cheng 1, Gang Ding 1,✉, Yong-Hua Ji 1,2,✉
PMCID: PMC5562571  PMID: 24132796

Abstract

The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I (10 μg), induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in lumbar 5–6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4EBP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses (spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity). Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.

Keywords: BmK I, mTOR, p70 ribosomal S6 protein kinase, 4E-binding protein 1, pain, dorsal root ganglion

Footnotes

These authors contributed equally to this work.

Contributor Information

Gang Ding, Email: ddinggang@hotmail.com.

Yong-Hua Ji, Email: yhji@staff.shu.edu.cn.

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