Activity-dependent changes in the pain matrix

Repetitive synaptic excitation or the application of L-glutamate into the v icinity of multireceptive neurons in the dorsal horn of the spinal cord and corresponding structures of the trigeminal nucleus increases neuronal exci tability, which is then reflected by an expansion of the receptive field (F ig. 1). Similar alterations of the receptive held of neurons have been obse rved in various other brain regions. The receptive fields of multireceptive neurons also expand their size following mechanical, chemical, inflammator y or nerve injuries. Since these multireceptive neurons are activated by co nverging non-nociceptive and nociceptive afferents an increased excitabilit y of these neurons may also be the mechanism by which pain refers to distan t somatic and Visceral structures (Fig. 2). The increase in neuronal excitability is mediated to a great extent by the co-activation of glutamate receptors and receptors for substance P, a neuro peptide long thought to have a role in pain perception. There is evidence f rom recent research that this facilitatory effect on glutamatergic synaptic transmission involves membrane receptor phosphorylation, and enhances acti vity-dependent gene expression (Fig. 3). In order to investigate the time-d ependent processing of ongoing afferent noxious stimulation in the central nervous system we recently employed the quantitative autoradiographic C-14- 2-deoxyglucose technique in a model of chronic monoarthritic pain in the ra t. A synopsis of these most recent experimental data and results from previ ous electrophysiological in vivo and in vitro studies suggests that dorsal horn neurons and probably also other neurons in pain-related structures bec ome spontaneously active and can maintain their activity without further no xious peripheral input.