GW4 BioMed2 MRC DTP PhD project: Brain stimulation and neurophysiological investigations of central nervous system changes in pathological pain, and their augmentation by treatment.

This project is one of a number that are in competition for funding from the GW4 BioMed2 MRC Doctoral Training Partnership which is offering up to 21 studentships for entry in September 2025.

The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. More information may be found on the DTP’s website.

Supervisory Team:

Dr Janet Bultitude (lead), University of Bath, Department of Psychology

Dr Sam Hughes, University of Exeter, Medical School

Dr Jennifer Davies, University of Cardiff

Professor Tony Pickering, University of Bristol

The Project: 

Chronic pain can involve changes throughout the central nervous system (CNS). Some treatments aim to alter CNS function, with limited results. This could be because research often investigates only one part of the CNS (e.g. cortex or spinal cord). This PhD will use brain stimulation, sensory testing, and neurophysiological methods to build an integrated understanding of changes in different levels of the CNS in chronic pain, and their modification by treatment.

Many chronic pain conditions cannot be explained by pathology in the painful body part, and are driven by central nervous system (CNS) changes at multiple levels (e.g. the brain, brainstem, and spinal cord). These can include changes in the motor and somatosensory systems, and in top-down endogenous pain modulation (the CNS mechanisms that augment pain signals from the limb to the brain via the spinal cord). Some treatments, such as spinal cord stimulation, aim to relieve pain in a limb by altering another part of the CNS. However, this requires invasive surgery. Other approaches recondition the motor system through behavioural training, however these are intensive and often provide little pain relief. A limitation in the current understanding is that CNS changes in pathological pain are usually measured in only one part of the CNS. A greater understanding of changes throughout the entire CNS, how these relate to activity in endogenous pain modulation systems, and how these are affected by CNS-targeting interventions, could help refine treatments. This PhD will address these gaps with a view to informing treatment.

Complex Regional Pain Syndrome (CRPS) will be our sample population because symptoms are severe but limited to one limb. This means the equivalent unaffected limb and corresponding nerves and brain areas can be used to collect within-subjects control data in addition to comparisons to pain-free controls.

In study 1, the student will examine changes to cortical function, central pain processing, and somatosensory and motor function in 50 people with CRPS and 50 pain-free controls. They will choose the measures during the ‘prep’ period. Likely candidates are:

– Transcranial Magnetic Stimulation (TMS) to measure the size and responsiveness of the representation of the affected limb on primary motor cortex (M1).

– Established protocols (e.g. conditioned pain modulation, temporal summation of pain) for assessing endogenous pain modulation.

– Quantitative Sensory Testing (QST) to gain an understanding of changes to somatosensory and pain processing. QST is a highly standardised psychophysical approach to measuring sensitivity to mechanical and thermal stimuli.

We expect that in CRPS (versus pain-free controls):

1) M1 for the affected limb will be smaller and more excitable,

2) there will be diminished endogenous pain inhibition, and

3) the affected limb will have greater QST sensitivity.

The student will also examine multivariate relationships between these measures, led by hypotheses generated during the ‘prep’ period.

Study 2 will be a pilot Randomized Controlled Trial to examine the effects of a CNS-targeting intervention on the same measures as used in study 1. The intervention will be 5 repeated daily sessions of transcranial direct current stimulation (tDCS) to M1. TDCS is thought to alter the resting membrane potential in the underlying cortex, increasing or decreasing the likelihood of action potentials. Daily tDCS to M1 may activate corticospinal and corticothalamic projections, which in turn influence the activity of regions of deeper brain areas, the brain stem, and the spinal cord involved in pain modulation mechanisms. However no study has investigated the effects of tDCS throughout multiple levels of the CNS. Also, daily sessions of tDCS to M1 decreases pain in people with chronic pain, although there are no mechanism-driven studies in people with CRPS. Twenty people with CRPS will be randomized to receive tDCS to M1 contralateral to their affected limb, or sham (placebo) stimulation. We hypothesise that tDCS will reduce pain (compared to sham). Exploratory analyses will investigate which CNS changes recover after treatment and whether any of these predict pain outcome.

This study will lead to a better understanding of the CNS mechanisms of tDCS treatment; the predictors of the effectiveness of the treatment; and the relationships between the motor, somatosensory, and endogenous pain modulation systems.

Requirements:

Applicants must have obtained, or be expected to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Applicants with a lower second class will only be considered if they also have a Master’s degree. Academic qualifications are considered alongside significant relevant non-academic experience.

Non-UK applicants will also be required to have met the English language entry requirements of the University of Bath.

Enquiries and Applications:

Informal enquiries are welcomed and should be directed to Dr Janet Bultitude j.bultitude@bath.ac.uk.

Formal applications must be submitted direct to the GW4 BioMed2 DTP using their online application form: GW4 BioMed MRC DTP – GW4 BioMed MRC DTP

A list of all available projects and guidance on how to apply may be found on the DTP’s website. You may apply for up to 2 projects.

APPLICATIONS CLOSE AT 17:00 (GMT) ON 4 NOVEMBER 2025.

IMPORTANT: You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application for an offer of study from Bath.