The encoding of noxious stimuli into action potential firing is largely mediated by nociceptive free nerve endings. We show that tissue inflammation-induced activation of the mammalian target of rapamycin complex 2 (mTORC2) triggers changes in the architecture of the nociceptive terminals and leads to inflammatory pain. Computational modelling demonstrated that mTORC2-mediated structural changes in the nociceptive terminal tree are sufficient to increase the excitability of nociceptive neurons. Targeting mTORC2 using a single injection of antisense oligonucleotide (ASO) against Rictor provided long-lasting alleviation of inflammatory pain hypersensitivity. Collectively, we show that tissue inflammation-induced activation of mTORC2 causes structural plasticity of nociceptive free nerve endings in the epidermis and inflammatory hyperalgesia, thus representing a new therapeutic target for inflammatory pain.