Tomivosertib reduces ectopic activity in dorsal root ganglion neurons from patients with radiculopathy.

ABSTRACT: Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined in preclinical models that drive spontaneous activity, none have been tested directly on spontaneously active human nociceptors. Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we showed that inhibition of mitogen-activated protein kinase interacting kinase (MNK) with tomivosertib (eFT508, 25 nM) reversibly suppresses spontaneous activity in human sensory neurons that are likely nociceptors based on size and action potential characteristics associated with painful dermatomes within minutes of treatment. Tomivosertib treatment also decreased act

SUBMITTER: Li Y 

PROVIDER: S-EPMC11370786 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature