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Original Report| Volume 12, ISSUE 2, P263-271, February 2011

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Formalin-Induced c-fos Expression in the Brain of Infant Rats

  • Gordon A. Barr
    Correspondence
    Address reprint requests to Dr Gordon A. Barr, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, 3615 Civic Center Blvd, ARC 716D, Philadelphia, PA 19104.
    Affiliations
    Department of Psychology, Biopsychology Doctoral Program, City University of New York, Hunter College, New York, NY
    Department of Developmental Psychobiology, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, NY
    Search for articles by this author
Published:December 13, 2010DOI:https://doi.org/10.1016/j.jpain.2010.09.005

      Abstract

      In the fetal, infant, and adult rat, injury induces a well-defined behavioral response and induces c-fos expression in the spinal cord dorsal horn. There is more limited information about the processing of noxious stimulation in the infant brain. We describe here the appearance of the Fos protein in the brain of fetal and infant rats following formalin-induced injury. Regions were chosen for analysis with a special focus on brain loci that express c-fos in the adult. No Fos positive cells were found in the brains of fetuses; newborns did not show increased Fos expression after formalin injection in any structure examined. At 3 and 14 days of age, there was a significant increase in Fos staining induced by formalin in the ventral lateral medulla. In contrast, paraventricular and medial dorsal nuclei of the thalamus, the paraventricular nucleus of the hypothalamus, and periaqueductal gray of the midbrain showed increased levels of Fos protein only at 14 days of age. We hypothesize that this developmental pattern is related not only to the maturation of pain perception but also to development of autonomic and defensive reactions to pain in the infant.

      Perspective

      Because the infant processes pain differently than the adult, knowledge of those differences informs pediatric clinical practice. Using Fos expression as a marker of neural activity in the rat, we show that the pattern of brain activation is immature at birth but is in place by 14 days of age.

      Key words

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      References

        • Anand K.J.
        • Garg S.
        • Rovnaghi C.R.
        • Narsinghani U.
        • Bhutta A.T.
        • Hall R.W.
        Ketamine Reduces the Cell Death Following Inflammatory Pain in Newborn Rat Brain.
        Pediatr Res. 2007; 62: 283-290
        • Andrews K.
        • Fitzgerald M.
        The cutaneous withdrawal reflex in human neonates–sensitization, receptive fields, and the effects of contralateral stimulation.
        Pain. 1994; 56: 95-101
        • Bandler R.
        • Depaulis A.
        Elicitation of intraspecific defence reactions in the rat from midbrain periaqueductal grey by microinjection of kainic acid, without neurotoxic effects.
        Neurosci Lett. 1988; 88: 291-296
        • Bandler R.
        • Shipley M.T.
        Columnar organization in the midbrain periaqueductal gray: Modules for emotional expression?.
        TINS. 1994; 17: 379-389
        • Barr G.A.
        Maturation of the biphasic behavioral and heart rate response in the formalin test.
        Pharmacol Biochem Behav. 1998; 60: 329-335
        • Bender M.
        • Drago J.
        • Rivkees S.A.
        D1 receptors mediate dopamine action in the fetal suprachiasmatic nuclei: Studies of mice with targeted deletion of the D1 dopamine receptor gene.
        Brain Res Mol Brain Res. 1997; 49: 271-277
        • Bullitt E.
        Induction of c-fos-like protein within the lumbar spinal cord and thalamus of the rat following peripheral stimulation.
        Brain Res. 1989; 498: 391-397
        • Campbell B.A.
        Dissociation of autonomic and behavioral components of conditioned fear during development in the rat.
        Behav Neurosci. 1985; 99: 1089-1102
        • Cannon J.T.
        • Prieto G.J.
        • Liebeskind J.C.
        Evidence for opioid and non-opioid forms of stimulation produced analgesia in the rat.
        Brain Research. 1982; 243: 315-321
        • Dostrovsky J.O.
        • Hu J.W.
        • Sessle B.J.
        • Sumino R.
        Stimulation sites in periaqueductal gray, nucleus raphe magnus and adjacent regions effective in suppressing oral-facial reflexes.
        Brain Res. 1982; 252: 287-297
        • Fitzgerald M.
        • Gibson S.
        The postnatal physiological and neurochemical development of peripheral sensory C-fibres.
        Neurosci. 1984; 13: 933-944
        • Gebhart G.F.
        • Ossipov M.H.
        Characterization of inhibition of the spinal nociceptive tail-flick reflex in the rat from the medullary lateral reticular nucleus.
        J Neurosci. 1986; 6: 701-713
        • Goodwin G.A.
        • Barr G.A.
        Behavioral and heart rate effects of infusing kainic acid into the dorsal midbrain during early development in the rat.
        Brain Res Dev Brain Res. 1998; 107: 11-20
        • Goodwin G.A.
        • Barr G.A.
        Developmental changes in the behavioral and autonomic effects of kappa opioid receptor stimulation of the midbrain periaqueductal gray.
        Dev Psychobiol. 2005; 46: 47-56
        • Guyenet P.G.
        • Darnall R.A.
        • Riley T.A.
        Rostral ventrolateral medulla and sympathorespiratory integration in rats.
        Am J Physiol. 1990; 259: R1063-R1074
        • Haroutunian V.
        • Campbell B.A.
        Development and habituation of the heart rate orienting response to auditory and visual stimuli in the rat.
        J Comp Physiol Psychol. 1981; 95: 166-174
        • Haroutunian V.
        • Campbell B.A.
        Neural control of the heart rate-orienting response in preweanling rats.
        Behav Neural Biol. 1982; 36: 24-39
        • Harrison D.
        • Yamada J.
        • Stevens B.
        Strategies for the prevention and management of neonatal and infant pain.
        Curr Pain Headache Rep. 2010; 14: 113-123
        • Herdegen T.
        • Rudiger S.
        • Mayer B.
        • Bravo R.
        • Zimmermann M.
        Increase in nitric oxide synthase and colocalization with Jun, Fos and Krox proteins in spinal neurons following noxious peripheral stimulation.
        Mol Brain Res. 1994; 22: 245-258
        • Hofer M.A.
        Early stages in the organization of cardiovascular control.
        Proc Soc Exper Biol Med. 1984; 175: 465-476
        • Hsu S.
        • Raine L.
        • Fanger H.
        Use of Avidin-Biotin-Peroxidase Complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures.
        J Histochem Cytochem. 1981; 29: 577-580
        • Hunt P.S.
        • Richardson R.
        • Campbell B.A.
        Delayed development of fear-potentiated startle in rats.
        Behav Neurosci. 1994; 108: 69-80
        • Ito A.
        • Miyoshi M.
        • Ueki S.
        • Fukada M.
        • Komaki R.
        • Watanabe T.
        “Green odor” inhalation by rats down-regulates stress-induced increases in Fos expression in stress-related forebrain regions.
        Neurosci Res. 2009; 65: 166-174
        • Jankord R.
        • Herman J.P.
        Limbic regulation of hypothalamo-pituitary-adrenocortical function during acute and chronic stress.
        Ann N Y Acad Sci. 2008; 1148: 64-73
        • Jasmin L.
        • Wang H.
        • Tarczyhornoch K.
        • Levine J.D.
        • Basbaum A.I.
        Differential effects of morphine on noxious stimulus-evoked fos-like immunoreactivity in subpopulations of spinoparabrachial neurons.
        J Neurosci. 1994; 14: 7252-7260
        • Jennings E.
        • Fitzgerald M.
        C-fos can be induced in the neonatal rat spinal cord by both noxious and innocuous peripheral stimulation.
        Pain. 1996; 68: 301-306
        • Jones S.L.
        • Blair R.W.
        Noxious heat-evoked fos-like immunoreactivity in the rat medulla, with emphasis on the catecholamine cell groups.
        J Comp Neurol. 1995; 354: 410-422
        • Kurtz M.M.
        • Campbell B.A.
        Paradoxical autonomic responses to aversive stimuli in the developing rat.
        Behav Neurosci. 1994; 108: 962-971
        • Lester L.S.
        • Fanselow M.S.
        Exposure to a cat produces opioid analgesia in rats.
        Behav Neurosci. 1985; 99: 756-759
        • Levine S.
        • Dent G.
        • De Kloet E.R.
        Stress-Hyporesponsive Period.
        in: Fink G. Encyclopedia of Stress. Academic Press, New York, NY2000: 518-526
        • McHaffie J.G.
        • Wang S.
        • Walton N.
        • Stein B.E.
        • Redgrave P.
        Covariant maturation of nocifensive oral behaviour and c-fos expression in rat superior colliculus.
        Neuroscience. 2002; 109: 597-607
        • McLaughlin C.R.
        • Lichtman A.H.
        • Fanselow M.S.
        • Cramer C.P.
        Tonic nociception in neonatal rats.
        Pharmacol Biochem Behav. 1990; 36: 850-862
        • Mitchell E.S.
        • Keller Jr., R.W.
        • Snyder-Keller A.
        Immediate-early gene expression in concurrent prenatal ethanol- and/or cocaine-exposed rat pups: Intrauterine differences in cocaine levels and Fos expression.
        Brain Res Dev Brain Res. 2002; 133: 141-149
        • Moriceau S.
        • Roth T.L.
        • Okotoghaide T.
        • Sullivan R.M.
        Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups.
        Int J Dev Neurosci. 2004; 22: 415-422
        • Oliveras J.L.
        • Besson J.M.
        • Guilbaud G.
        • Liebeskind J.C.
        Behavioral and electrophysiological evidence of pain inhibition from midbrain stimulation in the cat.
        Exp Brain Res. 1974; 20: 32-44
        • Oliveras J.L.
        • Woda A.
        • Guilbaud G.
        • Besson J.M.
        Inhibition of the jaw opening reflex by electrical stimulation of the periaqueductal gray matter in the awake, unrestrained cat.
        Brain Res. 1974; 72: 328-331
        • Ross C.A.
        • Ruggiero D.A.
        • Park D.H.
        • Joh T.H.
        • Sved A.F.
        • Fernandez-Pardal J.
        • Saavedra J.M.
        • Reis D.J.
        Tonic vasomotor control by the rostral ventrolateral medulla: Effect of electrical or chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin.
        J Neurosci. 1984; 4: 474-494
        • Ruigrok T.J.
        • Cella F.
        • Voogd J.
        Connections of the lateral reticular nucleus to the lateral vestibular nucleus in the rat. An anterograde tracing study with Phaseolus vulgaris leucoagglutinin.
        Eur J Neurosci. 1995; 7: 1410-1413
        • Saper C.B.
        The spinoparabrachial pathway: Shedding new light on an old path.
        J Comp Neurol. 1995; 353: 477-479
        • Sewards T.V.
        • Sewards M.A.
        Fear and power-dominance drive motivation: Neural representations and pathways mediating sensory and mnemonic inputs, and outputs to premotor structures.
        Neurosci Biobehav Rev. 2002; 26: 553-579
        • Sotgiu M.L.
        Inhibition of the nociceptive jaw opening reflex by the lateral reticular nucleus (LRN) in the rabbit.
        Neurosci Lett. 1986; 65: 145-148
        • Takahashi L.K.
        Stimulus control of behavioral inhibition in the preweanling rat.
        Physiology & Behavior. 1994; 55: 717-721
        • Takahashi L.K.
        • Turner J.G.
        • Kalin N.H.
        Development of stress-induced responses in preweanling rats.
        Deve Psychobiol. 1991; 24: 341-360
        • Tive L.A.
        • Barr G.A.
        Analgesia from the periaqueductal gray in the developing rat: Focal injections of morphine or glutamate and effects of intrathecal injection of methysergide or phentolamine.
        Brain Res. 1992; 584: 92-109
        • Wiedenmayer C.P.
        Adaptations or pathologies? Long-term changes in brain and behavior after a single exposure to severe threat.
        Neurosci Biobehav Rev. 2004; 28: 1-12
        • Wiedenmayer C.P.
        Plasticity of defensive behavior and fear in early development.
        Neurosci Biobehav Rev. 2009; 33: 432-441
        • Wiedenmayer C.P.
        • Barr G.A.
        Ontogeny of defensive behavior and analgesia in rat pups exposed to an adult male rat.
        Physiol Behav. 1998; 63: 261-269
        • Wiedenmayer C.P.
        • Barr G.A.
        Mu opioid receptors in the ventrolateral periaqueductal gray mediate stress-induced analgesia but not immobility in rat pups.
        Behav Neurosci. 2000; 114: 125-136
        • Wiedenmayer C.P.
        • Barr G.A.
        Developmental changes in c-fos expression to an age-specific social stressor in infant rats.
        Behav Brain Res. 2001; 126: 147-157
        • Wiedenmayer C.P.
        • Lyo D.
        • Barr G.A.
        Rat pups reduce ultrasonic vocalization after exposure to an adult male rat.
        Developmental Psychobiology. 2003; 42: 386-391
        • Williams S.
        • Evan G.
        • Hunt S.P.
        Spinal c-fos induction by sensory stimulation in neonatal rats.
        Neurosci Lett. 1990; 109: 309-314
        • Yi D.K.
        • Barr G.A.
        The induction of Fos-like immunoreactivity by noxious thermal, mechanical and chemical stimuli in the lumbar spinal cord of infant rats.
        Pain. 1995; 60: 257-265
        • Yi D.K.
        • Barr G.A.
        Formalin-induced c-fos expression in the spinal cord of fetal rats.
        Pain. 1997; 73: 347-354
        • Zimmermann M.
        • Herdegen T.
        Control of gene transcription by Jun and Fos proteins in the nervous system.
        APS Journal. 1994; 3: 33-48