The goal of my work is to understand the encoding process for nociceptive information to permit development of pharmacological therapies for the management of pain. My current work follows along three lines.
Pharmacology of afferent & spinal systems which process nociceptive information
A facilitated state of processing occurs with tissue and nerve injury. We have shown that these facilitated states reflect complex spinal cascades in which afferent transmitters activate downstream MAPKs which though PLA2 and COX 2 isozymes initiate spinal synthesis and release of a variety of lipidic acid mediators.
These studies have also emphasized the significance of microglia in this organization. As shown below, there is a low level of activated (phosphorylated) p38 MAPK in spinal dorsal horn following spinal injection of saline (A). Intrathecal substance P activates p38 MAPK in the spinal dorsal horn(B). The phosphorylated p38 MAPK colocalizes with microglia (D) but not with neurons(C). Using intrathecal antagonists and antisense, we showed that block of P38&beta isoform, located in microglia, is potently anti-hyperalgesic.