Basic Science |
Translational Research |
Clinical Research
Sex and pain
Recent studies indicate that neural mechanisms of pain and analgesia differ
in males and females. Inherent sex differences in neural function related to
pain make women more likely to develop deep tissue orofacial and visceral
persistent pain. These new findings will help target future therapies based
on sex and gender.
Joel Greenspan,
Richard Traub
Gonadal steroids and pain
Gonadal hormones play an important role in pain arising from the viscera.
Women are more prone to irritable bowel syndrome than men and symptoms
fluctuate with the menstrual cycle. Studies are examining the role of
estrogen and progesterone on visceral sensitivity and their possible
interaction with excitatory amino acids and their receptors. These
experiments will lead to new approaches to attenuating persistent visceral
pain and irritable bowel disease.
Richard Traub
Nociceptors and ion channels
Unique properties of peripheral sensory neurons that innervate specific
structures, such as the colon, jaw muscles, and the temporomandibular joint,
have been identified and likely contribute to persistent pain conditions. Novel
therapeutic targets based on regionally selective cellular and molecular
mechanisms in sensory neurons will lead to improvements in pain management.
Michael Gold,
Dean Dessem
Excitatory amino acid receptors and pain
Persistent activation of excitatory amino acid receptors in nociceptive pathways
leads to increases in synaptic strength and enhances responses to subsequent
nonpainful and painful stimuli. Novel receptor antagonists and inhibitors of
signal transduction will lead to improved approaches to attenuating pain and
hyperalgesia after injury without disturbing normal pain responses.
Guan Bai,
Ronald Dubner,
Ke Ren,
Feng Wei
Neonatal pain
Recent studies indicate that neonatal pain can lead to alterations in pain
processing in the adult. These findings stress the importance of developing
noninvasive and robust analgesic approaches in the neonate subject to injury and
pain.
Ronald Dubner,
Michael Gold,
Michael Lidow,
Ke Ren,
Richard Traub
Proinflammatory cytokines
Proinflammatory cytokines are associated with responses of the nervous system to
tissue or nerve injury. The cytokine cascade and its role in immune and neural
function is an important contributor to the development of persistent pain
states. These studies examine the contribution of peripheral and central nervous
system cytokine pathways to orofacial pain. The findings will lead to the
development of anti-inflammatory cytokines or their analogs as analgesic agents.
Ke Ren,
Ronald Dubner
Muscle pain
Persistent craniofacial muscle pain is a significant clinical program that
affects millions of Americans and leads to health care costs in the billions of
dollars. The underlying pathology of these conditions is poorly understood due
in part to the lack of appropriate experimental models to study mechanisms and
new treatment approaches. These studies will provide effective animals models
for understanding mechanisms and testing the efficacy of new analgesic agents.
Norman Capra,
Jin Ro
Descending sensory modulation
Tissue and nerve injury lead to an increase in the CNS descending modulation of
pain transmission to higher brain centers. The changes are dynamic with
descending excitation or inhibition dominating depending on the type of injury.
The changes involve increased activation of excitatory amino acid and opioid
receptors. The development of strategies to alter descending modulation after
injury will provide more effective treatments of deep tissue persistent pain.
Ronald Dubner,
Ke Ren,
Feng Wei
Craniofacial dysfunction and pain
The muscles of mastication and the temporomandibular joint are prominently
involved in mechanisms of persistent orofacial pain. These conditions impact on
patterns of jaw movement, which are altered by the presence of pain. Tongue
movements are also altered by pain leading to disordered speech, dental
anomalies and changes in respiration and swallowing. An understanding of oral
and craniofacial motor function and the influence of pain are important in order
to develop treatment approaches that restore normal jaw relationships.
Norman Capra,
Jin Ro
Communication between immune and nervous systems
Neural-inflammatory interactions play a prominent role in the pathophysiology of
complex diseases such as bronchial asthma. Therefore, understanding how the
immune and nervous systems communicate with each other at the cellular level
will provide new strategies for developing novel therapeutic approaches to a
myriad of hypersensitivity and inflammatory diseases.
Daniel Weinreich
Neural networks in the mammalian olfactory system
All biological systems share common mechanisms at the cellular and molecular
levels yet exhibit tremendous diversity of organization and function. This
diversity arises at the level of cell-cell communication. The most complex
degree of cell-cell communication is in the nervous system. This complexity is
expressed in the brain at the level of neural networks. Neural networks are the
unique, defining characteristic of the nervous system. Understanding the
organization, function and development of neural networks in the mammalian
olfactory system is the center of this research. In vivo recording methods are
used to understand how cell-cell communication and neural networks are involved
in the neural computation of odorants.
Michael Shipley
CNS control of reproductive function
The CNS control of reproductive function has currently evolved into studying the
processing of excitatory stimuli to the neurons that contain luteinizing hormone
releasing hormone (LHRH or gonadotropin releasing hormone, GnRH) and trigger
ovulation. Neuronal phenotype changes induced by the suckling stimulus in the
prolactin regulatory neurons during lactation are also addressed, using new
quantitative non-radioactive in situ hybridization methods. A separate but
related direction of this research also focuses on the consequences of ovarian
function on the injured brain. These studies examine the role that ovarian
hormones play in pain, seizure-induced brain damage, and neuronal damage induced
by CNS inflammatory disease experimental allergic encephalitis.
Gloria Hoffman