1Xinhua Hospital (Chongming) Affi liated to Shanghai Jiao Tong University School of Medicine; Shanghai Chongming Xinhua Translational Medical Institute for Cancer Pain, Shanghai 202150, China
2Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China
#These authors contributed equally to this work.

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-4E-BP1 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 specifi c inhibitor of mTOR, attenuated BmK I-induced pain responses (spontaneous fl inching, 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

[SpringerLink]