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
Headache Prophylaxis By Cortico-brainstem Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$616,437.00
Summary
In this project we hope to discover the cause of migraine headache. Many triggers lead to migraine, but we do not know how. We believe the triggers produce a defect in pain control by the brainstem, which normally keeps sensation from the head below the pain threshold. In migraine, trigger factors acting high in the brain open a pain control gate lower in the brain, producing a migraine headache. If we can prove this, we can develop therapies that will prevent migraine before it starts.
Improving Oral health is a priority of the NHMRC Strategic Plan 2003-06. The proposed research is consistent with this priority as we will achieve a better understanding of the cortical control of human jaw muscles, which serves as the foundation for understanding conditions in which their function is impaired, and the development of rational therapies for these conditions. Transcranial magnetic stimulation will be used to activate the motor cortex and corticobulbar descending pathway to the jaw ....Improving Oral health is a priority of the NHMRC Strategic Plan 2003-06. The proposed research is consistent with this priority as we will achieve a better understanding of the cortical control of human jaw muscles, which serves as the foundation for understanding conditions in which their function is impaired, and the development of rational therapies for these conditions. Transcranial magnetic stimulation will be used to activate the motor cortex and corticobulbar descending pathway to the jaw muscles. The AIM 1 study will provide important new information about the functional organisation of the motor cortex in the control of jaw muscles during speech. This information is needed to improve understanding of dysarthria, a common disturbance of speech due to impaired muscular control following unilateral cortical stroke, and less common conditions involving speech motor control such as spasmodic dysphonia (a cranial dystonia) and dysprosody (disturbance of speech articulation and rhythm found in Parkinson s disease). The AIM 2 and 3 studies will provide a comprehensive characterization of cortical inhibitory mechanisms that are an important but poorly understood component of the cortical control of jaw muscles. This information is necessary to understand normal function, and the mechanisms of disturbances to jaw muscle function with neurological disease or injury. The AIM 4 studies will show whether impaired cortical inhibition contributes to the pathophysiology of two poorly understood disorders affecting jaw muscles (bruxism and oromandibular dystonia). Current therapies for these conditions are unsatisfactory, due to a limited understanding of the mechanisms involved. If cortical inhibition is abnormal in these conditions this will lead to novel treatment therapies (e.g., drugs to correct the imbalance, or strategies to induce plastic change in the cortex).Read moreRead less
Effects Of Muscle Inflammation On Sensory Neuron Excitability
Funder
National Health and Medical Research Council
Funding Amount
$397,398.00
Summary
Muscle pain is a common and poorly treated health problem for many Australians. This project examines the properties of nerves that sense muscle pain and looks at how these change during inflammation, a common cause of muscle pain. We are looking specifically at jaw muscles, which are one of the most common sites of chronic muscle pain. By understanding how muscle nerves are changed by injury, we hope to be able to develop treatments to prevent or reverse these changes.
Speech and chewing are accomplished automatically by the jaw muscles which have both the power to chew meat and even bone, and the precision to make extremely fine adjustments to the shape of the mouth that enable speech. The brain needs constant inputs from sensory receptors in and around the mouth to control these muscles. We will investigate how these sensory mechanisms automatically fine-tune the activity of the jaw muscles and the mechanisms that keep the jaw in its normal position when the ....Speech and chewing are accomplished automatically by the jaw muscles which have both the power to chew meat and even bone, and the precision to make extremely fine adjustments to the shape of the mouth that enable speech. The brain needs constant inputs from sensory receptors in and around the mouth to control these muscles. We will investigate how these sensory mechanisms automatically fine-tune the activity of the jaw muscles and the mechanisms that keep the jaw in its normal position when the subject is sitting quietly, or when the head is moving up and down during running. This normal rest position of the jaw is a vital point of reference for dentists who are making false teeth and for surgeons who are restoring damaged faces, but it is not known what mechanisms are responsible for it. Anyone who has experienced a sore tooth or sore jaw muscles will know that pain adversely affects normal chewing. A common symptom is limitation of jaw movements. We will determine how pain affects the control of jaw muscles. This is important for people with chronic facial pain from arthritis of the jaw joint or from grinding their teeth while they are asleep. Even if it is not possible to eliminate their pain, we hope to suggest approaches which will alleviate its effects. Another part of our study involves a computer model of the chewing system. Computer models enable scientists to examine the effect of various interventions such as surgery or orthodontics on a model before these are tried on humans. It is also possible to use such a virtual patient to answer important functional questions that cannot be examined in humans because the methods are unavailable, or because the procedures would be ethically unacceptable. The current version of the computer model is quite sophisticated anatomically, but lacks important information on the control systems that activate the muscles. We will collaborate with the developers of the model by providing this information.Read moreRead less