Regulation of CREB phosphorylation by TrkB receptor activity for neurotrophins in dorsal spinal cord after peripheral nerve injury

Abstract

Neuropathic pain is an intractable, chronic syndrome that may arise from injury to peripheral nerves and is associated with allodynia, hyperalgesia, spontaneous pain, repetitive discharge of nociceptors and the expansion of receptive fields of nociceptive input. Our understanding of the pathophysiology of this debilitating syndrome is very limited and represents the main obstacle to the development of more effective therapeutic strategies. Recently, in vitro studies indicated that TrkB neurotrophin receptor strongly modulate monoamineric activity, suggesting a communication between two different classes of receptors. In the present study, we will explore the functional consequences of this interaction in an animal model of neuropathic pain. The main objectives of the project are: (1) to investigate TrkB-dependent CREB phosphorylation in the spinal cord dorsal horn following chronic nerve lesion.(2) the effect of chronic administration of serotonin/noradrenaline reuptake inhibitor on TrkB-dependent CREB phosphorylation in the spinal cord dorsal horn following chronic nerve lesion.This project aims at delineating new, fundamental neurobiological mechanisms underlying chronic pain. Most important, this project may reveal novel mechanistically based targets for development of more effective and specific analgesic drugs.