Dental Injury Models: Experimental Tools for Understanding Neuroinflammatory Interactions and Polymodal Nociceptor Functions

It has been suggested that the proto-oncogenes c-fos and c-myc participate in the control of genetic events which lead to the establishment of prolonged functional changes in neurons. Expression of c-fos and c-myc are among the earliest genetic events induced in cultured fibroblast and phaeochromocytoma cell lines by various stimuli including growth factors, peptides and the intracellular second messengers diacylglycerol, cAMP and Ca2+. We report here that physiological stimulation of rat primary sensory neurons causes the expression of c-fos-protein-like immunoreactivity in nuclei of postsynaptic neurons of the dorsal horn of the spinal cord. Activation of small-diameter cutaneous sensory afferents by noxious heat or chemical stimuli results in the rapid appearance of c-fos-protein-like immunoreactivity in the superficial layers of the dorsal horn. However, activation of low-threshold cutaneous afferents results in fewer labelled cells with a different laminar distribution. No c-fos induction was seen in the dorsal root ganglia, gracile nucleus or ventral horn. Thus, synaptic transmission may induce rapid changes in gene expression in certain postsynaptic neurons.

It has recently become accepted that the activated immune system communicates to brain via release of pro-inflammatory cytokines. This review examines the possibility that pro-inflammatory cytokines (interleukins and/or tumor necrosis factor) mediate a variety of commonly studied hyperalgesic states. We will first briefly review basic immune responses and inflammation. We will then develop the concept of illness responses and provide evidence for their existence and for the dramatic changes in neural functioning that they cause. Lastly, we will examine the potential roles that both pro-inflammatory cytokines and the neural circuits that they activate may play in the hyperalgesic states produced by irritants, inflammatory agents, and nerve damage. The possibility is raised that apparently diverse hyperalgesic states may converge in the central nervous system and activate similar or identical neural circuitry.