Research Projects
Elucidating the Role of Fasting Mimicking Diet in Reactive Astrocytes Polarisation of Neuropathic Pain: Mechanistic Insight and Preclinical Translation

Central/peripheral nerve injury or tissue damage causes central neuropathic pain (CNP), which are characterized by long term allodynia (pain behaviour evoked by non-noxious stimuli) and hyperalgesia (exaggerated pain behaviour evoked by noxious stimuli). These syndromes bring negative impacts on cognitive, physical and emotional functioning for patients. Current treatments for neuropathic pain can only relieve pain to a certain degree, and often cause early refractory symptoms or some can have harmful or uncomfortable side effects, such as increased risk of heart and blood vessel disorders, endocrine, immunologic, and psychological side effects.

In recent years, multiple studies have revealed that painful neuropathy is highly associated with metabolic factors, including diabetes, high-fat diet/glucose intake, aging as well as metabolites mediated PH. Furthermore, metabolic dysfunctions have been reported in chemotherapy induced pain or HIV-associated sensory neuropathy. In humans, mutations in mitochondrial genes frequently result in the development of painful peripheral syndromes, as seen in patients with charcot-marie-tooth disease. Emerging evidences reinforce the notion that shifts in carbon metabolism play essential roles in the regulation of cellular properties during pathological transitions in neurological disorders. Drug or small molecules inventions and energy-based diet therapy for targeting metabolic reprogram have advanced the treatment of various diseases in recent years. Thus, elucidating metabolic alterations during pain pathogenesis and molecular mechanisms would shed some new light on pain management by developing alternative strategies.

Objective:

1. To investigate the effects of low calorie and low protein fasting mimicking diet cycles as a treatment of neuropathic pain mouse models.

2. To elucidate how energy based therapy can modulate the reactive astrocytes A1/A2 polarization which plays important roles for neuro-inflammation and neuroprotective switching.

3. To unravel the underlying molecular mechanisms involved, and establish scientific basis for future clinical trials and studies.

Significance:

In majority of pain-associated syndromes, A1/A2 polarization of astrocytes are determining their status to be neuro-inflammatory or neuro-protective, which is critical for pain production and persistence. Drug or small molecules inventions and energy based diet therapy for targeting metabolic reprogram have advanced the treatment of various neurological disorders in recent years. Mitochondrial and bioenergetics dysfunctions are reported in painful neuropathy. Despite this, molecular changes as well as underlying mechanisms in mediating metabolic changes upon pain development is largely unknown. The work will provide a new insight into pain management as a way to better understand disease states, with the long term goal of developing new drugs or energy based therapy for patients suffering neuropathy.

Research Plan and Methodology:

The student(s) will design a research proposal based on the laboratory facility and accomplish this research project under mentor’s supervision through below methodologies:

1. Building up the animal model of neuropathic pain and applying low calorie and low protein fasting mimicking diet cycles.

2. Multiple behavioural tests will be applied to evaluate pain responses under different treatments.

3. Molecular analysis, including q-PCR, Western Blot and immunohistochemistry, will be applied to investigate the changes in signalling molecules and cellular events upon pain induction with or without fasting mimicking diet.

Professor CW Cheung, Department of Anaesthesiology

Biography
cheucw@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.