Sensitivity to pain and c-Fos expression in brain structures in rats.

The induction of c-Fos protein--a product of the c-fos gene, a marker of changes in neuronal activity, was studied in brain structures of animals differing in their sensitivity to the acute painful stimulation, a foot-shock (MS--more sensitive rats; LS--less sensitive rats, according to the arbitrary criterion in the flinch-jump pretest). After the pretest the animals were dived into the control group, exposed on retest 10 days later to the testing cage only (C1 group), and aversively stimulated animals (MS and LS groups, given five mild footshocks 1.5 h before immunocytochemical part of the experiment). Additional control group of naive, intact animals, was studied in parallel (C group). It was shown that animals subjected to the flinch-jump test retained a strong emotional reaction on re-exposure to the shock cage on retest (a conditioned fear) 10 days later, as revealed by the widespread expression of c-Fos protein in the examined brain structures, as compared with the control, naive rats not exposed to the testing cage. In the lateral habenular nucleus (LHAB) a similar effect has been found in the control animals re-exposed to the testing cage only (C1 group), and in the MS group, suggesting that this brain area participates predominantly in processing of emotional-cognitive component of a painful stimulation. In the periaqueductal gray and basolateral nucleus of amygdala the most pronounced, but significantly higher in comparison with C group only, expression of c-Fos was detected in MS rats. Interestingly, a strong and uniform enhancement of c-Fos expression appeared in all other brain structures examined, including cortical areas, indicating their sensitivity to non-direct (conditioned) aversive stimuli. The only significant difference in c-Fos expression between LS and MS rats found in LHAB points to this brain structure as selectively engaged in processing of the emotional-cognitive component of a painful stimulation. The reactivity of LHAB may be responsible for the genetically determined differences in sensitivity to pain.