mTORC2 in inflammatory and neuropathic pain
A pain that persists for more than 3 months is termed chronic pain. The protein kinase mammalian target of rapamycin (mTOR) and its downstream effectors have been shown to play key roles in sustaining pain hypersensitivity in cases of inflammatory and neuropathic pain.
Intrathecal administration of the mTOR inhibitor rapamycin has been found to block the spread of hypersensitivity into undamaged cutaneous areas.
The mTOR kinase operates within two distinct protein complexes known as mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The role of mTORC2 in inflammatory and neuropathic pain has received less attention.
The authors show that mTORC2+ excitatory neurons may form synapses with calretinin+ neurons to mediate mechanical allodynia caused by tissue inflammation. On the other hand, mTORC2+ inhibitory neurons may form synapses with PKC-γ neurons to mediate mechanical allodynia caused by peripheral nerve injury.
Further mechanistic studies are required to validate these pain regulatory pathways.
https://academic.oup.com/brain/article/148/2/675/7738209
https://sciencemission.com/target-of-rapamycin-complex-2-alleviates-pain
