Common patterns of increased and decreased fos expression in midbrain and pons evoked by noxious deep somatic and noxious visceral manipulations in the rat

J Comp Neurol. 1996 Mar 11;366(3):495-515. doi: 10.1002/(SICI)1096-9861(19960311)366:3<495::AID-CNE9>3.0.CO;2-#.


Immunohistochemical detection of the protein product (Fos) of the c-fos immediate early gene was used to study neuronal activation in the rostral pons and midbrain of halothane-anesthetised rats following noxious deep somatic or noxious visceral stimulation. In animals exposed only to halothane anesthesia, Fos-like immunoreactive (IR) neurons were located in the midbrain periaqueductal gray matter, tectum, and parabrachial nucleus. Following noxious stimulation of hindlimb muscle, knee joint, vagal cardiopulmonary, or peritoneal nociceptors, there was, compared to halothane-only animals, a significant increase in the numbers of Fos-like (IR) cells in the caudal ventrolateral periaqueductal gray and the intermediate gray lamina of the superior colliculus. Given the general agreement that increased Fos expression is a consequence of increased neuronal activity, the finding that a range of noxious deep somatic and noxious visceral stimuli evoked increased neuronal activity in a discrete, caudal ventrolateral periaqueductal gray region is consistent with previous suggestions that this region is an integrator of deep noxious evoked reactions. The noxious deep somatic and noxious visceral manipulations also evoked, compared to halothane-only animals, reductions in the numbers of Fos-like IR cells in the stratum opticum of the superior colliculus and the unlaminated portion of the external subnucleus of the inferior colliculus. To our knowledge this is the first report of reductions in Fos-expression in the tectum evoked by noxious stimulation. In separate experiments, the effects of noxious deep somatic and noxious visceral manipulations on arterial pressure and heart rate were measured. The noxious visceral manipulations evoked substantial and sustained falls in arterial pressure (15-45 mmHg), and heart rate (75-100 bpm), whereas the depressor and bradycardiac effects of the noxious deep somatic manipulations were weaker, not as sustained, or entirely absent. As similar distributions and numbers of both increased and decreased Fos-like IR cells were observed after each of the deep noxious manipulations, it follows that the deep noxious evoked increases and decreases in Fos expression were not secondary to the evoked depressor or bradycardiac effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / physiology
  • Evoked Potentials, Somatosensory / physiology
  • Heart Rate / physiology
  • Immunohistochemistry
  • Inferior Colliculi / chemistry
  • Inferior Colliculi / metabolism
  • Locus Coeruleus / chemistry
  • Locus Coeruleus / metabolism
  • Male
  • Mesencephalon / chemistry*
  • Mesencephalon / metabolism
  • Nociceptors / physiology
  • Pain / physiopathology
  • Periaqueductal Gray / chemistry
  • Periaqueductal Gray / metabolism
  • Pons / chemistry*
  • Pons / metabolism
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-fos / chemistry
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Rats, Sprague-Dawley / physiology*
  • Superior Colliculi / chemistry
  • Superior Colliculi / metabolism
  • Viscera / innervation


  • Proto-Oncogene Proteins c-fos