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
Neural Mechanisms Underlying Human Grasp And Manipulation
Funder
National Health and Medical Research Council
Funding Amount
$396,100.00
Summary
We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well ....We rely on hand function in a multitude of simple tasks that we tend to take for granted but that are essential in our everyday lives; some examples are turning on a tap, doing up shoelaces, or holding a cup. Many people in the community are disabled by impaired hand function resulting from lesions of the central nervous system or peripheral nerve lesions. The size of the problem is enormous; manual dexterity is affected in approximately 20,000 new stroke patients each year in Australia as well as in other neurological diseases such as neuropathies, nerve injuries, cerebral palsy and many others. The broad aim of this study is to investigate the poorly understood neural mechanisms that underlie sensorimotor control of hand function. We will target a specific aspect of manual dexterity that is crucial for the execution of common everyday tasks, like pouring liquid from a bottle, in which the digits are subjected to torsional loads. In order to maintain stable grasps, the motor control system must rapidly and automatically adjust the grip forces employed to meet the demands imposed by the changing torsion. This is only possible because of sensory feedback from the hand, a large component of which arises from the cutaneous mechanoreceptive afferent fibres. In the first two years we will use a combined approach of neural recording from peripheral nerves in anaesthetised monkeys and psychophysics experiments in normal humans to answer the general question: how does the population of cutaneous afferents provide precise feedback about torsion on the digits? In the third year we will perform key experiments in humans, using microneurography to record from their peripheral nerves. This will establish any differences between human and monkey mechanoreceptors.Read moreRead less
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
Staying Connected: Personalising Stroke Recovery And Rehabilitation Through New Technologies For People With Stroke Living At Home.
Funder
National Health and Medical Research Council
Funding Amount
$1,730,999.00
Summary
One in 4 people experience a stroke. On return home the person with stroke is challenged to sense, move, think, and engage in valued activities with an altered brain and body. Yet the current approach to ongoing recovery is limited. We propose to: monitor for markers of recovery using personalised sensors and artificial intelligence; deliver bursts of therapy at point of need, at home; and provide feedback through new technologies and a central hub...to stay connected, and to recover at home.
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.
We stand without falling by using silent senses from muscles and the balance organs of the inner ear to unconsciously detect and control our movements. Since the leg muscles provide both the force and the sense, and critically rely on good circulation, they are vitally important. I propose to study how these sensory and muscle functions are used to control balance, posture and stepping reflexes, making it easier to identify older people who will fall and design new preventative strategies.