Project ID NS-MH2023_03


Co Supervisor 1A IoPPN/Wolfson CARDWebsite

Co Supervisor 1B IoPPN/NeuroimagingWebsite

How does the brain control pain? Mapping pain processing in health and disease

The unique experience of pain is driven in part by the descending pain modulatory system (DPMS). Activity in DPMS-encompassed descending inhibitory pathways is altered in some chronic pain states. This PhD proposal is concerned with mapping the mechanisms that underlie DPMS dysfunctionality in the transition from health to disease.

The student will train in cutting-edge skills (surgical techniques, electrophysiology, and functional magnetic resonance imaging (fMRI)). Specifically, they will define DPMS circuitry using rodent neuroimaging to generate new whole system level knowledge of DPMS functionality by:

Year 1-2 Measuring functional connectivity (FC) by fMRI focusing on cortical-brainstem connections in healthy rats upon application of key paradigms known to evoke activity in distinct DPMS circuits (3 distinct circuits will be investigated). Thereafter, for comparison, the student will focus on:

Year 2-3 Determining the relative FC between key cortical and brainstem regions in an animal model of neuropathic pain (where dysfunctionality in the DPMS is evidenced). By investigating activity in multiple circuits in healthy and chronic pain rats, the student will be able to map plasticity in key brain regions known to govern pain processing. In addition, optogenetics and electrophysiology may be combined with fMRI to experimentally modulate the relevant circuitry and monitor brain-wide outputs. For example, if a cortical deficit is found in in one of the circuits, does opto-manipulation of key sites reinstate normal functional activity?

The Bannister and Cash labs have a great track record in generating high impact results and publications and in training, supervising, and supporting PhD students.

One representative publication from each co-supervisor:

Distinct brainstem to spinal cord noradrenergic pathways inversely regulate spinal neuronal activity. Kucharczyk M, Di Domenico F, Bannister K. Brain 2022 (doi: 10.1093/brain/awac085)

Duricki, D.A., Drndarski, S., Bernanos, M., Wood, T., Bosch, K., Chen, Q., Shine, H.D., Simmons, C., Williams, S.C.R., McMahon, S.B., Begley, D.J., Cash, D., Moon, L.D.F., 2019. Stroke Recovery in Rats after 24-Hour–Delayed Intramuscular Neurotrophin-3 Infusion. Ann Neurol 85, 32–46.