Sympathetic microneurography and its application to understanding pain in Postural Tachycardia Syndrome (PoTS)
Supervisors: Dr Yoko Nagai, Dr A Dilley, Prof H Critchley, Dr J Eccles
Application deadline: Friday, May 31, 2024 Competition Funded PhD Project (UK Students Only)
About the Project
Postural orthostatic tachycardia syndrome (PoTS)1,2 is a form of dysautonomia, a condition characterised by differences in autonomic reactivity and symptoms such as dizziness on standing. PoTS is associated with fibromyalgia3, a chronic widespread pain condition, and is more common in people with variant connective tissue (manifest as Joint Hypermobility)4,5. Understanding the link between dysautonomia and pain is clinically importance for the better management of symptoms that give rise to of disability and impair poor quality of life. Autonomic cardiovascular arousal, reflecting the action sympathetic nerves, and body-to-brain (interoceptive) feedback of this arousal, influence the experience of pain. For many people, increases in blood pressure, signalled through arterial baroreceptor firing at systole, can inhibit pain processing6 but, in some people with chronic pathological pain conditions, this can intensify pain7. Blood pressure is part-regulated by muscle sympathetic nerve activity (MSNA), constricting vascular beds. The technique of microneurography can enable direct measurement of MSNA8.9, which can provide fine-grained insight into stress-sensitivity and individual differences2,3,8,9. This PhD project will use sympathetic microneurography to define mechanisms of interaction between pain processing and autonomic dysregulation that can account for fibromyalgia and experience of pain symptoms in patients with PoTS. With support from the Autonomic Charitable Trust and input from expert collaborators, we propose to train a scientist to doctoral level in the use of sympathetic microneurography and its application to understanding autonomic/pain interaction in PoTS.
The PhD will;
1) provide mechanistic insight into autonomic modulation of pain in PoTS and fibromyalgia;
2) enable the piloting of biobehavioural interventions10 that may help with dysautonomia and pain management;
3) strengthen collaboration between autonomic research centres nationally and internationally.
Entry requirements
This studentship is suitable for those with background in neuroscience, physiology or another relevant subject area. We invite applications from students who have received or are on target to achieve a relevant undergraduate degree with minimum 2:1 classification (or equivalent). An MSc and previous experience in experimental research studies, ideally in humans, are desirable but not essential.
How to apply
Applicants must apply through the University of Brighton application portal (StudentView, brighton.ac.uk) where they can submit a CV and complete the application form. The deadline for applications is 31st May 2024. Interviews will be held in June 2024. Informal enquiries are welcome and should be submitted to Professor Hugo Critchley h.critchley@bsms.ac.uk or Professor Andrew Dilley a.dilley@bsms.ac.uk.
Funding notes
This is a 3-year PhD studentship funded jointly by the Baroness Susan Masham Autonomic Charitable Trust Research Award and by Brighton and Sussex Medical School to start between July and October 2024. Funding covers tuition fees for UK students (at the Home rate), a stipend at the UKRI rate, and research running costs. International applicants are welcome to apply but will be required to cover the difference between Home and International fees.The funding also supports and essential training component in the laboratory of Professor Vaughan Macefield, Baker Institute, Monash University Melbourne to which the capacity to travel is required.
References
1) Postural tachycardia syndrome--current experience and concepts. Mathias CJ et al Nat Rev Neurol. 2011 8:22-34.
2) Sympathetic nerve activity in response to hypotensive stress in the postural tachycardia syndrome. Bonyhay I, Freeman R.Circulation. 2004 110:3193
3) Hyperexcitable C nociceptors in fibromyalgia. Serra J, et al Ann Neurol 2014 75196- 208.
4) Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and EhlersDanlos syndrome hypermobility type): Clinical description and natural history. Tinkle B, et al., Am J Med Genet C Semin Med Genet. 2017 175:48-69.
5) Joint hypermobility syndrome. Psychiatric manifestations. Eccles J, et al BMJ. 2011 342: d998.
6) Baroreceptor activation attenuates attentional effects on pain-evoked potentials. Gray MA, et al., Pain. 2010 151:853-6.
7) Sympathetic nervous system: contribution to chronic pain. Jänig W, Häbler HJ. Prog Brain Res. 2000; 129:451-68.
8) Sympathetic microneurography. Macefield VG. Handb Clin Neurol. 2013;117:353-64
9) Physiological and pathophysiological firing properties of single postganglionic sympathetic neurons in humans. Macefield V, Wallin B. J Neurophysiol. 2018 119:944-56.
10) Epileptic seizures are reduced by autonomic biofeedback therapy. Nagai Y et al., EBioMedicine. 2018 27:112-122.