Start of funding 01.07.2003

Activation of mitogen activated protein (MAP) kinases in primary sensory neurons and spinal cord associated with neuropathic pain

Dr. Maria Schäfers
University of Würzburg
Neurologische Klinik und Poliklinik

Prof. Dr. Claudia Sommer
University of Würzburg
Neurologische Klinik und Poliklinik

Prof. Dr. Linda S. Sorkin
University of California, San Diego
Anesthesiology Research Laboratory



Peripheral nerve injury often results in neuropathic pain associated with hyperalgesia and allodynia. Several lines of evidence suggest that proinflammatory cytokines such as tumor necrosis factor-alpha (TNF), which are released into the local milieu following injury, may initiate a cascade that underlies this facilitated processing. Downstream targets of cytokine activation are mitogen-activated protein kinases (MAPK), which have been recently shown to play a major role in the maintenance of pain arising from inflammation or nerve injury. As MAPKs initiate changes in transcription and post-translational processes, they are candidates to alter receptors, neurotransmitters and/or channels in primary afferents or dorsal horn that contribute to spinal sensitization and enhanced pain behavior. In the proposed collaboration with Prof. Dr. Sorkin, University of San Diego, California, we will investigate molecular mechanisms by which proinflammatory cytokines such as TNF modulate neuronal activity and trigger changes in transcription as well as post-translational modifications of target proteins in dorsal root ganglia and spinal cord that are correlated with the development of pain after nerve injury.