Activity-dependent changes in the pain matrix.

Abstract

Repetitive synaptic excitation or the application of L-glutamate into the vicinity of multireceptive neurons in the dorsal horn of the spinal cord and corresponding structures of the trigeminal nucleus increases neuronal excitability, which is then reflected by an expansion of the receptive field (Fig. 1). Similar alterations of the receptive field of neurons have been observed in various other brain regions. The receptive fields of multireceptive neurons also expand their size following mechanical, chemical, inflammatory or nerve injuries. Since these multireceptive neurons are activated by converging non-nociceptive and nociceptive afferents an increased excitability of these neurons may also be the mechanism by which pain refers to distant 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 neuropeptide long thought to have a role in pain perception. There is evidence from recent research that this facilitatory effect on glutamatergic synaptic transmission involves membrane receptor phosphorylation, and enhances activity-dependent gene expression (Fig. 3). In order to investigate the time-dependent processing of ongoing afferent noxious stimulation in the central nervous system we recently employed the quantitative autoradiographic 14C-2-deoxyglucose technique in a model of chronic monoarthritic pain in the rat. A synopsis of these most recent experimental data and results from previous electrophysiological in vivo and in vitro studies suggests that dorsal horn neurons and probably also other neurons in pain-related structures become spontaneously active and can maintain their activity without further noxious peripheral input.