Biology subjects

Hughes, S. W.

Publications and source records attributed to Hughes, S. W..

3 recordsLinked to original sources

bioRxiv2025

Profiling trait and state-like behaviour in pain modulation systems: a role for effective connectivity within endogenous pain control circuits

Endogenous pain modulation systems can be assessed through distinct psychophysical paradigms such as conditioned pain modulation (CPM), temporal summation of pain (TSP), and offset analgesia (OA). Notably, the reliability of these measures has rarely been defined within the same participants, and measures to index the consistency of each measure across sessions and in the same participants are lacking. This study examined the test-retest reliability and intra-individual consistency of CPM, TSP, and OA and explored how CPM response status across sessions relates to neural dynamics within the descending pain modulation system. In 29 healthy participants, CPM, TSP, and OA responses were assessed across two sessions. The normalised session change index (NSCI) was introduced to evaluate consistency of each measure across sessions. Spectral dynamic causal modelling (DCM) of resting-state fMRI (rs-fMRI) investigated effective connectivity within the descending pain modulation network and its association with CPM response status. OA exhibited the highest test-retest reliability and had NSCI values closest to zero, indicating stable responses. CPM and TSP showed poor reliability and NSCI values deviating from zero, reflecting greater variability. Spectral DCM analysis revealed that effective connectivity within the descending pain modulation system explained CPM response variability across sessions. Specifically, consistent strong facilitatory or inhibitory CPM was associated with greater excitatory or inhibitory PAG-to-AI effective connectivity, respectively. These findings suggest that healthy participants either demonstrate stable (i.e. trait-like) or dynamic (i.e. state-like) endogenous pain modulation across repeated sessions which can be explained based on effective connectivity within the descending pain modulation system.

neuroscience↗

bioRxiv2025

Investigating the influence of experimentally induced central sensitisation on pain prediction error encoding in healthy individuals: a novel virtual reality protocol

Persistent mismatches between predicted and actual pain-related signals, namely prediction errors (PEs), can cause maladaptive overestimation of pain intensity, a common feature of chronic pain states. Experimental protocols used to assess the contribution of central sensitisation (CS) to dysregulated prediction systems are lacking. To address this, we implemented a novel virtual reality (VR) paradigm to evoke PEs during mechanical stimulation following experimentally induced CS via the high-frequency stimulation (HFS) model. Twenty healthy volunteers underwent HFS on the right forearm. Mechanical pain sensitivity (MPS) was assessed through pinprick stimuli before and 30 minutes post-HFS to evaluate secondary hyperalgesia. Following this, participants received mechanical stimuli at proximal (sensitised area) and distal (non-sensitised area) points from the HFS site, with visual cues presented on their arm via VR alongside hand tracking technology indicating the stimulus location, allowing participants to make pain predictions. Cues were either congruent (matching) or incongruent (mismatching) with the actual stimulus site, to evoke PEs. Results showed that MPS significantly increased following HFS, confirming secondary hyperalgesia. Stimuli in sensitised areas induced more pain than in non-sensitised areas. Incongruent cues successfully elicited PEs across all locations, however, expectations modulated pain perception only in non-sensitised areas. Similarly, during incongruent trials, PEs diminished over time (reflecting adaptive learning) only in non-sensitised areas. These data demonstrate that pain expectations can influence pain perception differently in centrally sensitised and non-sensitised states. We propose this protocol as a good candidate to assess how cognitive and psychological manipulations influence PEs at various stages of CS.

neuroscience↗

bioRxiv2024

Neural Dynamics of Tonic Cold Pain: A Novel Investigation of an In-Scanner Alternative to the Cold Pressor Test in Healthy Individuals

The cold pressor task (CPT) is widely used to study tonic pain during acute and chronic conditions and is often as used as a conditioning stimulus to activate descending pain control systems. However, logistical challenges in magnetic resonance imaging (MRI) limit its application, hindering the understanding of CPTs neural dynamics. To address this, we acquired resting-state functional MRI data from 30 healthy participants before, during, and after immersion in gelled-cold water, the closest in-scanner alternative to date to CPT for prolonged stimulation. Participants provided subjective pain intensity ratings after each scan, as well as average pain perceived during noxious stimulation, using a numeric rating scale (NRS). Following fMRI, participants rated their pain continuously during identical tonic noxious stimulation of the contralateral hand using a visual analogue scale (VAS). We employed three complementary methods to examine changes in brain function across fMRI conditions: a data-driven approach via independent component analysis (ICA), seed-to-whole-brain connectivity analysis with the periaqueductal grey (PAG) as seed, and spectral dynamic causal modelling (spDCM) to explore effective connectivity changes across the dorsal anterior cingulate cortex (dACC), anterior insulae (AI), thalamus, and PAG. NRS scores were significantly higher following tonic cold compared to baseline and recovery conditions. Continuous VAS reflected sustained mild-to-moderate pain over six minutes, with average VAS scores not significantly differing from NRS ratings recorded in the scanner. ICA identified engagement of descending pain control and sensorimotor networks during pain, with the latter persisting during recovery. Seed-based analysis revealed a disengagement between the PAG and cortical/subcortical regions involved in pain processing, such as the dACC, midcingulate cortex, AI, intraparietal sulcus, and precuneus. Finally, spDCM revealed tonic pain neural signature was most likely characterised by top-down inhibitory and bottom-up excitatory connections. This study establishes the cold gelled-water paradigm as a robust in-scanner alternative to CPT. By uncovering key neural dynamics of CPT, we provide new insights into the brain and brainstem mechanisms of tonic cold pain paradigms routinely used in psychophysical pain studies. Key pointsO_LIImmersion in gelled-cold water is a reliable in-scanner substitute for the cold pressor task, enabling prolonged tonic cold pain research in MRI. C_LIO_LIKey neural dynamics, such as PAG-driven excitatory inputs and AI-mediated inhibitory control, were identified, providing new insights into cold pain modulation. C_LIO_LIBy taking a multi-method approach, including ICA, seed-based connectivity, and DCM, we offer a comprehensive view of the neural networks involved in tonic cold pain, bridging neuroimaging and behavioural research. C_LI

neuroscience↗