Targeting spinal mechanistic target of rapamycin complex 2 alleviates inflammatory and neuropathic pain

Chronic pain involves changes in spinal nociceptive circuits. The mechanistic target of rapamycin complex 2 (mTORC2) modulates structural changes and mRNA translation. Activation of spinal mTORC2 induces pain hypersensitivity. Inhibiting it, using Rictor downregulation, alleviates inflammatory and neuropathic pain. Inhibiting mTORC2 in specific excitatory neurons impairs spinal synaptic potentiation. This alleviates inflammation-induced mechanical and thermal hypersensitivity and nerve injury-induced heat hyperalgesia.

• 1
  Pharmacological activation of spinal mTORC2 induces pain hypersensitivity.
• 2
  Inhibition of mTORC2, via Rictor downregulation, alleviates both inflammatory and neuropathic pain.
• 3
  Selective mTORC2 inhibition in excitatory neurons alleviates inflammation-induced mechanical/thermal hypersensitivity and nerve injury-induced heat hyperalgesia.