Research
Developmental Psychobiology
The general topic of study by this lab
is how the development of neural and other physiological
processes result in behavioral and physiological maturation.
To that end, we study behavior within a developmental
framework and examine how the maturation of biological
systems that might cause those changes. This approach
lends itself to the use of a variety of behavioral,
anatomical, pharmacological, and genetic methods, all
of which can be brought to bear on the biological question
of interest. Below are the areas of long standing interest.
 Opiate
Abstinence and Tolerance
Large numbers of seriously ill infant
patients are treated with opiates to alleviate pain,
and other human infants are exposed in utero to illicit
opiate drugs such as heroin and to prescribed opiates
such as methadone. It is therefore important to understand
the effects of acute and chronic exposure to drugs such
as these on the immature organism. A necessary step
in defining the long term effects of drug exposure early
in development is to describe fully how the drug acts
on neurobehavioral systems in the neonate. We have found
that the infant undergoes a distinct opiate withdrawal,
but that the signs and symptoms experienced by the neonate
differ from those suffered by the adult. Nonetheless,
the infant in abstinence shows developmentally appropriate
behavioral signs of withdrawal, increased crying and
a negative affective state. Further, the infant also
becomes tolerant to the analgesic effects of opiates,
but to a lesser degree than does the adult. We are currently
working to define the neural and molelcular substrates
of opiate withdrawal in the infant. We have found that:
- The neuroanatomical loci underlying
withdrawal is similar in the infant and adult.
- The mu opioid receptor is critical
for both.
- But, the role of glutamate receptors
differs significantly in mediating both withdrawal
and tolerance.
- Intracellular signaling cascades engaged
by chronic opiate administration change during early
development
- The pattern of gene expression differs
in the infant and the adult.
Nociception
The issue of how noxious stimuli are processed
at various levels of the neuroaxis has been the subject
of intense study for decades and significant progress
has been made in our understanding of how noxious sensations
are perceived, processed and dampened. Yet little is
known of how pain processing differs between immature
and adult organisms.  The
question of whether or not infants even experience pain
has been controversial. Not long ago the prevailing
medical opinion was that human infants did not perceive
pain due to the immature state of their nervous system,
and in particular the lack of myelination of axons.
This assumption led directly to the inappropriate withholding
of analgesics for painful surgical treatments. Recent
studies have shown that the requisite pathways for the
transmission of pain from the periphery to the central
nervous system develop perinatally, but a detailed understanding
of how these input systems become organized is still
lacking. Further, the early experience of pain may result
in long term reorganization and functional alterations
in the experience of pain. Understanding how pain sensation
develops is a necessary first step in the development
of appropriate therapeutic interventions to alleviate
pain and suffering in the human neonate. To that end
we are currently defining the changes in gene expression
that occur following tissue injury in the infant and
adult animal using microarray technology.
 Analgesia
The problems of how to provide safe and
effective analgesia for human infants are difficult
because a major class of analgesic drugs, the opiates,
act differently in the infant patient than they do in
the adult patient. Furthermore, the relationship of
unwanted side effects to therapeutic effects changes
with age. Classically, opiates have been known to induce
analgesia by acting on the central nervous system and
a major part of our work is aimed at understanding how
those neural systems function during early development.
The full description of changes in nociception, opiate
induced antinoception, opioid peptide and receptor regulation
will provide important information on the development
of opiate induced pain relief in both human infants
and adults.
Methods
To study these questions we use a variety
of behavioral, anatomic, pharmacologic, electrophysiologic
and genetic tools. We carefully study the behavior of
the animal to define in detail the phenomenon under
investigation. We use: 1). a variety of anatomic tools
to define brain and spinal cord regions involved in
withdrawal, nociception and analgesia; 2). current pharmacologic
tools to assess the role of cellular receptors and messengers;
3). field potentials from the spinal cord dorsal horn
to define the changes in glutamate regulation of tolerance
and withdrawal; 4) “knock-out” mice to study
the changing role of neurokinins in nociception; and
5) microarray studies to identify changes in gene expression
patterns as a function of age in both the processing
of noxious information and in the development of opiate
tolerance and withdrawal.
Please contact Gordon Barr, Ph.D., if
interested. gbarr@hunter.cuny.edu
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