student profile: Mrs Aimie Peek


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Thesis work

Thesis title: Brain Neurochemicals in Migraine, Whiplash with Headache and Low back pain

Supervisors: Trudy REBBECK , Kathryn REFSHAUGE , Andrew LEAVER

Thesis abstract:

Migraine, whiplash and low back pain together form the highest musculoskeletal burden. However, the underpinning mechanisms are poorly understood. As a result treatments are often aimed at symptoms of the chronic condition such as pain or distress rather than the underlying mechanism. Consequently, randomised controlled trials of best available evidence demonstrate modest results at best. In order to improve health outcomes a better understanding of the underlying mechanisms of chronic pain conditions is required.

This thesis aims to gain a better understanding of the underlying mechanisms of migraine and an insight into other chronic pain conditions. The supervisory team have identified a promising mechanism in migraine. They found that the main inhibitory neurotransmitter, Gama-aminobutyric acid (GABA) was increased, whilst the main excitatory neurotransmitter (Glutamate) remained stable in people with migraine when compared to controls. This forms the first of three stages of validation for determining an underlying mechanism or biomarker. Stage two is to determine if these changes are present in other headache or pain conditions, and the final, third stage is to see if GABA and glutamate are sensitive to change in clinical characteristics over time. This thesis will provide evidence to support or refute the theory that increased GABA could be an underpinning mechanism of migraine.

This PhD thesis will look to gain a better understanding of the mechanisms underpinning migraine through the following six studies;

1. A systematic review: Brain GABA and glutamate levels across pain conditions: Systematic review and meta-analysis of 1HMRS studies.

This review aims to synthesise the current literature to determine if changes in GABA and glutamate differ in people experiencing pain and pain free controls. Secondly it will determine if the concentration of GABA and Glutamate differ between different pain conditions, whilst providing a critical evaluation of the Magnetic Resonance Spectroscopy (MRS) parameters used.

2. A Cross Sectional Study: Brain neurochemicals in migraine, whiplash and back pain

This study will aim to determine if changes in GABA and Glutamate concentration are unique to migraine or if they are present in other headache or pain conditions. This forms the second stage of biomarker validation.

3. A Cross Sectional Study: The Association between Clinical Characteristics of Pain Conditions and Braine GABA and Glutamate levels.

This will be an exploratory study that will aim to determine if GABA or Glutamate concentrations are associated with musculoskeletal impairments or pain sensitivity tests. This study will serve to further validate GABA and a Glutamate as potential biomarkers of migraine, or pain conditions.

4. An exploratory study: Does Salivary GABA and glutamate levels correlate with Magnetic resonance spectroscopy (MRS) measures within the brain.

This will be a lab based study on 80 participants who will provide a saliva sample prior to undertaking MRS. This study will serve to see if salivary GABA and glutamate levels can correlate with those determined through MRS of the brain. Should correlation be demonstrated then salivary analysis will offer an economical, practical option that will allow monitoring of GABA throughout the ictal period.

5. A longitudinal study: Changes in GABA and Glutamate in pain conditions over time.

This study will serve as stage 3 of validation of a biomarker for migraine. It will determine if GABA and Glutamate are sensitive to changes in clinical characteristics over time. Should the measure prove to be sensitive in detecting change it will demonstrate significant potential as a biomarker of migraine or pain.

6. A cross sectional study: Determining how pain influences performance of clinical tests of headache

This study will examine the clinical characteristics shown to be associated with changes in GABA and Glutamate levels to determine if these changes are specific to headache or related to the presence of pain in general. This will provide further validation as to whether changes in GABA and Glutamate are specific to migraine, headache or pain in general.

In conclusion this thesis has the ability to provide preliminary data supporting or refuting GABA and Glutamate’s role in migraine. Furthermore, it will contribute significantly to the current knowledge of mechanisms underpinning migraine, and could therefore be used to help develop treatments that target the underlying cause of migraine.

Selected publications

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Journals

  • Miller, C., Peek, A., Power, D., Heneghan, N. (2017). Psychological consequences of traumatic upper limb peripheral nerve injury: A systematic review. Hand Therapy, 22(1), 35-45. [More Information]
  • Peek, A., Stevens, M. (2016). Different forms of exercise for chronic low back pain (PEDro synthesis). British Journal of Sports Medicine, 50(3), 188-188. [More Information]
  • Peek, A., Stevens, M. (2016). Resistance training for people with Parkinson's disease (PEDro synthesis). British Journal of Sports Medicine, 50(18), 1158-1158. [More Information]
  • Peek, A., Miller, C., Heneghan, N. (2015). Thoracic manual therapy in the management of non-specific shoulder pain: A systematic review. The Journal of Manual and Manipulative Therapy, 23(4), 176-187. [More Information]

2017

  • Miller, C., Peek, A., Power, D., Heneghan, N. (2017). Psychological consequences of traumatic upper limb peripheral nerve injury: A systematic review. Hand Therapy, 22(1), 35-45. [More Information]

2016

  • Peek, A., Stevens, M. (2016). Different forms of exercise for chronic low back pain (PEDro synthesis). British Journal of Sports Medicine, 50(3), 188-188. [More Information]
  • Peek, A., Stevens, M. (2016). Resistance training for people with Parkinson's disease (PEDro synthesis). British Journal of Sports Medicine, 50(18), 1158-1158. [More Information]

2015

  • Peek, A., Miller, C., Heneghan, N. (2015). Thoracic manual therapy in the management of non-specific shoulder pain: A systematic review. The Journal of Manual and Manipulative Therapy, 23(4), 176-187. [More Information]

Note: This profile is for a student at the University of Sydney. Views presented here are not necessarily those of the University.