Research Professor of PharmacologyEnhanced neuronal activity, driven by ectopic discharge of injured or adjacent fibers following injury to peripheral nerves results in increased input to spinal dorsal horn and to the nucleus gracilis (NG) via the dorsal column. Such inputs to the NG are likely to be transmitted to other supraspinal sites, possibly to the thalamus via the medial lemniscus (ML). Inputs to supraspinal sites are likely to result ultimately in enhanced descending facilitation from the RVM. This is because injection of lidocaine or CCK2 antagonists into the RVM, or lesioning MOR expressing cells in the RVM, or lesioning the DLF all blocks enhanced pain. These data suggest that descending facilitation may be driven by CCK in the RVM, and may be mediated by descending facilitatory cells that express mu opioid receptors (MOR). Our studies thus identify the critical neurocircuit that promotes abnormal pain, within which novel therapeutic strategies may be derived (abridged from Porreca et al. 2002. Trends Neurosci 25: 319-325).
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