Elsevier

Neuroscience

Volume 133, Issue 1, 2005, Pages 231-243
Neuroscience

A brainstem substrate for analgesia elicited by intraoral sucrose

https://doi.org/10.1016/j.neuroscience.2005.01.055Get rights and content

Abstract

Previous studies demonstrated that nursing or intraoral infusion of certain components of mother’s milk (e.g. sugars and fats) produces calming and opiate receptor-dependent analgesia in newborn rats and humans. However, the neural circuitry underlying such analgesia is unknown. The aim of the present study was to specify the central pathways by which taste stimuli engage neural antinociceptive mechanisms. For this purpose, midcollicular transactions were used to investigate the role of the forebrain in analgesia elicited by intraoral infusion of 0.2 M sucrose in neonatal rats. Sucrose-induced analgesia persisted, and was enhanced, following midcollicular transection, indicating that it did not require neural circuits confined to the forebrain. Fos immunohistochemistry was used to identify brainstem neurons activated by a brief (90 s) intraoral infusion of a small volume (90 μl, 0.2M) of sucrose or a salt solution (0.1 M ammonium chloride) in 10-day-old rat pups. Compared with control groups (intact, cannula, distilled water), both sucrose and ammonium chloride induced Fos expression in the rostral nucleus tractus solitarius, the first relay in the ascending gustatory pathway. Sucrose also elicited Fos expression in several brainstem areas associated with centrally mediated analgesia, including the periaqueductal gray and the nucleus raphe magnus. Taken together, these findings demonstrate that analgesia elicited by intraoral sucrose does not require involvement of the forebrain. Intraoral sucrose activates neurons in the periaqueductal gray and nucleus raphe magnus, two key brainstem sites critically involved in descending pain modulation.

Section snippets

Animals and intraoral cannulation

Male and female Sprague-Dawley rat pups (Zivic Miller Co.; Harlan, Indianapolis) at postnatal days 10–12 were housed with their mother in standard polypropylene cages until the day of the experiments. Experimental procedures were carefully conducted in order to minimize animal discomfort and the number of animals used, according to an institutionally approved protocol conforming with local and international guidelines on the ethical use of animals. P10–12 pups were used because analgesia

Effects of midcollicular transections on analgesia elicited by intraoral sucrose

Midcollicular transections or sham procedures were performed in P10–12 pups (n=24). Behavioral data presented below for the transection group are summarized from a total of 12 pups in which histological analyses demonstrated the transections to be complete. A representative example of a midcollicular transection is shown in Fig. 1. The effects of intraoral infusions on withdrawal response frequency to a series of sub- to suprathreshold von Frey filaments in cannulated animals before and after

Discussion

A major finding of the present study is that analgesia elicited by intraoral sucrose in neonatal rat pups is produced by a neural substrate limited to the brainstem and spinal cord. Midcollicular transection, which severs brainstem antinociceptive and gustatory circuits from the mid- and forebrain, enhanced analgesia elicited by intraoral infusion of sucrose. Fos staining demonstrated that intraoral sucrose increased neuronal activity in a number of structures caudal to the transection that

Acknowledgments

We thank David Letizia for assistance with Fos quantification, Becky Wade for help with histology and Adam Puche for help with photography. This work was supported by PHS grants DC03895, NS41384, and FAPESP 97/11034-7.

References (86)

  • E.M. Blass et al.

    Interactions between sucrose, pain and isolation distress

    Pharm Biochem Behav

    (1987)
  • P.M. Di Lorenzo et al.

    Transfer of information about taste from the nucleus of the solitary tract to the parabrachial nucleus of the pons

    Brain Res

    (1997)
  • M. Dragunow et al.

    The use of c-fos as a metabolic marker in neuronal pathway tracing

    J Neurosci Methods

    (1989)
  • M. Ennis et al.

    Discrete subregions of the rat midbrain periaqueductal gray project to nucleus ambiguus and the periambigual region

    Neuroscience

    (1997)
  • M. Fitzgerald et al.

    The functional development of descending inhibitory pathways in the dorsolateral funiculus of the newborn rat spinal cord

    Dev Brain Res

    (1986)
  • B.G. Gray et al.

    Inhibition of feline spinal cord dorsal horn neurons following electrical stimulation of nucleus paragigantocellularis lateralisa comparison with nucleus raphe magnus

    Brain Res

    (1985)
  • H.J. Grill et al.

    The taste reactivity test: I. Mimetic responses to gustatory stimuli in neurologically normal rats

    Brain Res

    (1978)
  • H.J. Grill et al.

    The taste reactivity test: II. Mimetic responses to gustatory stimuli in chronic thalamic and chronic decerebrate rats

    Brain Res

    (1978)
  • C.B. Halsell et al.

    Gustatory and tactile stimulation of the posterior tongue activate overlapping but distinctive region within the nucleus of the solitary tract

    Brain Res

    (1993)
  • C.B. Halsell et al.

    Ascending and descending projections from the rostral nucleus of the solitary tract originate from separate neuronal populations

    Neuroscience

    (1996)
  • M.I. Harrer et al.

    Topographic organization of Fos-like immunoreactivity in the rostral nucleus of the solitary tract evoked by gustatory stimulation with sucrose and quinine

    Brain Res

    (1996)
  • M.M. Heinricher et al.

    Microinjection of morphine into nucleus reticularis paragigantocellularis of the ratsuppression of noxious-evoked activity of nucleus raphe magnus neurons

    Brain Res

    (1985)
  • A. Heller et al.

    Stereotaxic electrode placement in the neonatal rat

    J Neurosci Methods

    (1979)
  • D.M. Hermann et al.

    Afferent projections to the rat nuclei raphe magnus, raphe pallidus and reticularis gigantocellularis pars alpha demonstrated by iontophoretic application of choleratoxin (subunit b)

    J Chem Neuroanat

    (1997)
  • P.W. Kalivas et al.

    Antinociception after microinjection of neurotensin into the central amygdaloid nucleus of the rat

    Brain Res

    (1982)
  • T.L. Krukoff et al.

    Efferent projections from the parabrachial nucleus demonstrated with the anterograde tracer Phaseolus vulgaris leucoagglutinin

    Brain Res Bull

    (1993)
  • S.T. Meller et al.

    Afferent projection to the periaqueductal gray in the rabbit

    Neuroscience

    (1986)
  • Menescal-de-Oliveira et al.

    Temporal activation of antinociception by reciprocal connections between the dorsomedial medulla and parabrachial region

    Brain Res Bull

    (1995)
  • R. Norgren et al.

    The pontine taste area in the rat

    Brain Res

    (1975)
  • J.L. Oliveras et al.

    Stimulation-produced analgesia in animalsbehavioral investigations

    Prog Brain Res

    (1988)
  • K. Ren

    An improved method for assessing mechanical allodynia in the rat

    Physiol Behav

    (1999)
  • M. Sheng et al.

    The regulation and function of c-fos and other immediate early genes in the nervous system

    Neuron

    (1990)
  • A. Tarasiuk et al.

    Descending inhibition in neonatal rat spinal cordactions of pentobarbital and morphine

    Brain Res Bull

    (1996)
  • L.A. Tive et al.

    Analgesia from the periaqueductal gray in the developing ratfocal injections of morphine or glutamate and the effects of intrathecal injection of methysergide or phentolamine

    Brain Res

    (1992)
  • H. van Praag et al.

    The development of stimulation-produced analgesia (SPA) in the rat

    Dev Brain Res

    (1991)
  • T. Yamamoto et al.

    Comparison of c-Fos-like immunoreactivity in the brainstem following intraoral and intragastric infusion of chemical solutions in rats

    Brain Res

    (2000)
  • J.B. Williams et al.

    Demonstration of a bilateral projection from the rostral nucleus of the solitary tract to the medial parabrachial nucleus in rat

    Brain Res

    (1996)
  • D.X. Zhang et al.

    Short-latency excitatory postsynaptic potentials are evoked in primate spinothalamic tract neurons by corticospinal tract volleys

    Pain

    (1991)
  • V.C.Z. Anseloni et al.

    C-Fos immunoreactivity and analgesia induced by sucrose infusion in 10-day-old rats

    (1999)
  • D. Bajic et al.

    Periaqueductal gray neurons monosynaptically innervate extranuclear noradrenergic dendrites in the rat pericoerulear region

    J Comp Neurol

    (2000)
  • A.I. Basbaum et al.

    Endogenous pain control systemsbrainstem spinal pathways and endorphin circuitry

    Ann Rev Neurosci

    (1984)
  • M.M. Behbehani et al.

    Interactions between the lateral hypothalamus and the periaqueductal gray

    J Neurosci

    (1988)
  • H. Bester et al.

    Spino (trigemino) parabrachiohypothalamic pathwayelectrophysiological evidence for an involvement in pain processes

    J Neurophysiol

    (1995)
  • Cited by (70)

    • Energy conservation in infants

      2015, Behavioural Processes
    • C-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats

      2015, Brain Research Bulletin
      Citation Excerpt :

      One approach in identifying neural substrates mediating sugar intakes is the c-Fos technique, a marker of neuronal activity (e.g., Dragunow and Faull, 1989; VanElzakker et al., 2008). Thus, sucrose intake increased Fos-like immunoreactivity (FLI) in the central gustatory system (Anseloni et al., 2005; Schwarz et al., 2010), the central nucleus of the amygdala (AMY), the ventral tegmental area (VTA) as well as the shell, but not core, of the nucleus accumbens (NAc) (Norgren et al., 2006; Park and Carr, 1998; Zhao et al., 2011), implicating orosensory and post-ingestive influences. Sucrose intake in sham-feeding rats significantly increased FLI in the AMY and the NAc, but not the VTA (Mungarndee et al., 2008), implicating orosensory influences.

    View all citing articles on Scopus
    View full text