c-fos, An immediate early gene as a neuromarker for nociception

Abstract

Pain is a complex experience that involves sensorial and affective components, and is composed by displeasure sensation, which are important for human being. Clinical manifestation of pain may be understood as the expression of nervous system ability for plastic response. There is evidence showing that nocive stimulation could also induce long-term variation in CNS cellular processes by modulating the expression of immediate early genes such as c-fos and c-jun. Fos protein distribution in CNS areas following heat nocive stimulation includes: 1)structures involved in emotional responses that seem to play a role in the affective component of pain (amygdaloid complex, hypothalamus, and cortical limbic structures); 2) structures usually responsible for descending pain control systems, that also play a role in the affective component of pain (periaqueductal gray and raphe nuclei); and 3) regions with evidence of taking part on the modulation of nociceptive impulse (periaqueductal gray and anterior pretectal nucleus). Expression of Fos protein in CNS following nocive stimuli may also be related to neuroplasticity in pathological pain and hiperalgesia, as well as to the prolific effect of the “pre-emptive” analgesia in pain following surgeries. In addition, as a nuclear “third messenger”, c-fos could stimulate synthesis of opioid peptide, which would play a role in pain modulation. Finally, this gene could be used as a transinaptic marker for neuronal activity, which allow the study of large neuronal population of structures that are activated by periferic stimulation.