Fig. 4.1.

In the peripheral termini of WT sensory neurons, Fmrp facilitates the transport and translational repression of mRNA destined for the axon. Injury, cytokines such as IL-6, and the mGluR1/5 agonist DHPG activate various kinases that increase the excitability of sensory neurons by modulating the activity of TRPV1 and other ion channels. Moreover, activated kinases can induce the initiation of translation [via increased eIF4F complex formation (4 F)], leading to the local synthesis of pronociceptive proteins that enhance and maintain nociceptive sensitization of the primary afferents. In contrast, absence of Fmrp results in the dysregulation of mRNA trafficking and translational repression. Hence, nociceptive inputs that induce prolonged sensitization of the primary afferents may not efficiently induce the local translation of pronociceptive proteins. This results in abrogated responses to injury, IL-6, and DHPG in Fmr1 KO mice