Trigeminal pain includes such disorders as headache, migraine, trigeminal neuralgia, dental and temporomandibular joint pain. These disorders affect more than 10 % of the population and many of the afflicted get only partial relief from current treatments. Trigeminal pain is conveyed from the head to the brain via primary afferent nerves. Work in the current proposal focuses on transmission of information in the brainstem as well as in the primary afferent nerves. Previously our group has report ....Trigeminal pain includes such disorders as headache, migraine, trigeminal neuralgia, dental and temporomandibular joint pain. These disorders affect more than 10 % of the population and many of the afflicted get only partial relief from current treatments. Trigeminal pain is conveyed from the head to the brain via primary afferent nerves. Work in the current proposal focuses on transmission of information in the brainstem as well as in the primary afferent nerves. Previously our group has reported that adenosine- 5' triphosphate (ATP) causes an increase in excitatory neurotransmission from primary afferent nerves; such an increase has been reported to be painful in previous human and animal studies. Recently we have shown that the ATP induced increase in neurotransmission is dependant on activation of a specific excitatory receptor, the N-methyl D aspartate (NMDA) receptor, which has been widely implicated in other brain functions such as memory, and in disorders such as neuron death following stroke. The chief investigators involved in this application plan to study the role of the ATP receptor and the interaction with NMDA receptors in an inflammatory trigeminal pain model. Electrophysiological, pharmacological and immunohistochemical studies will be performed in order to address the aims of this proposal. A greater understanding of how these receptors modulate neurotransmission in pain pathways will lead to a greater understanding of trigeminal pain and the potential development of new therapeutics.Read moreRead less
Fetomaternal Immunological Interactions In The Aetiology Of Allergic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$195,990.00
Summary
There is accumulating evidence that immune abnormalities that lead to allergy are present at birth, and may be linked with maternal factors in pregnancy. This study examines how immune interactions between the fetus and the mother during pregnancy predispose to allergic immune responses in the infant. Allergic diseases result from inappropriate Type 2 responses to the environment whereas Type 1 response dominate immune responses of nonallergic people. Type 2 immune responses are first initiated ....There is accumulating evidence that immune abnormalities that lead to allergy are present at birth, and may be linked with maternal factors in pregnancy. This study examines how immune interactions between the fetus and the mother during pregnancy predispose to allergic immune responses in the infant. Allergic diseases result from inappropriate Type 2 responses to the environment whereas Type 1 response dominate immune responses of nonallergic people. Type 2 immune responses are first initiated before birth when they are actually normal for fetal survival. In normal infants maturation of Type 1 immune responses plays a central role in switching off the Type 2 responses of fetal life. Allergic disease appears to be due to abnormal persistence of this Type 2 response pattern beyond the newborn period. One of the most striking abnormalities in allergic individuals is immature Type 1 function at birth. With rising rates of allergy, there is an urgent need to identify how the balance of Type 1 and Type 2 responses is regulated during this early period. Maternal factors appear to play a critical role. There is already evidence that Type 1 responses are lower in babies of allergic mothers compared to babies of allergic fathers, suggesting direct effects of the mother in pregnancy. Although pregnancy normally favours Type 2 immunity, there appears to be normal variation in the balance of Type 1 and Type 2 responses in pregnancy. We plan to determine if variations in this balance affect the fetal capacity for Type 1 responses. We propose that minor degrees of tissue mismatch (present in all pregnancies) will activate low grade Type 1 responses and enhance maturation of fetal Type 1 responses. We will determine if allergic mothers (prone to stronger Type 2 responses) have less developed Type 1 responses in pregnancy and if this plays a direct role in abnormal Type 1 responses observed in their babies.Read moreRead less