Utilising Functional MRI and Psychophysics to Decode the Descending Pain Modulation System
Poster No:
2511
Submission Type:
Abstract Submission
Authors:
Joseph Taylor1, Sonia Medina-Hernandez2, Olivia Kowalcyck1, Alessandra Venezia1, Fawsitt-Jones Harriet1, Elena Makovac3, Timothy Lawn1, Kirsty Bannister1, Steven Williams1, Matthew Howard1
Institutions:
1King's College London, London, 2Exeter Univeristy, Exeter, 3Brunel University, London
First Author:
Co-Author(s):
Introduction:
Conditioned pain modulation (CPM), a proposed measure of the efficiency of a person's descending pain modulatory system (DPMS), refers to the phenomenon of increased pain thresholds and decreased intensity ratings in response to a given stimulus when applied in conjunction with a second noxious stimulus, compared to when applied in isolation. Dysfunction in this system has been reported in a variety of patient populations, but the results from these populations remain equivocal [1].
We used well-characterised noxious pressure stimulation, known to elicit robust and reliable responses in the brain [2] and a randomised, event-related fMRI design. It was hypothesised that pain ratings to unilateral pressure stimuli would be reduced in the presence of a concurrent noxious stimulus, and that such reductions would be underpinned by cortical, midbrain and brainstem circuitry posited to be involved in endogenous pain control [3].
We used well-characterised noxious pressure stimulation, known to elicit robust and reliable responses in the brain [2] and a randomised, event-related fMRI design. It was hypothesised that pain ratings to unilateral pressure stimuli would be reduced in the presence of a concurrent noxious stimulus, and that such reductions would be underpinned by cortical, midbrain and brainstem circuitry posited to be involved in endogenous pain control [3].
Methods:
50 participants completed a pain modulation paradigm involving delivery of a noxious "Test Stimulus" in the presence and absence of a concurrent noxious "Conditioning Stimulus", using custom designed thumb stimulators. Test and Conditioning stimuli were 2 and 8 seconds in duration respectively. The pressure eliciting approximately a 6/10 pain rating was titrated for each hand, then used as stimulation intensity. 36 stimuli were presented in a pseudorandomised trial structure, of "Test" trials, in which the test stimulus was presented on its own, and "Test+" trials, in which the test stimulus was presented with the conditioning stimulus. For every trial, participants rated the painfulness of the test stimulus, ignoring the conditioning stimulus, using a Visual Analogue Scale (VAS), anchored with 'no pain at all' and 'worst pain imaginable'.
BOLD data were acquired at 3T and pre-processed using in FSL. First level explanatory variables (EVs) included the task regressors for Test, and Test+ trials and rating periods. Contrasts were performed for each trial type in isolation against baseline, with the main contrasts of interest being the two trial types compared against each other.
Two first level analyses were performed: i) standard task analysis, ii) parametric modulation using first level trial-by-trial VAS ratings. For both, a second-level analysis was performed to derive mean brain activity across the group. Cluster significance was inferred at a family-wise error rate corrected threshold of 0.05.
BOLD data were acquired at 3T and pre-processed using in FSL. First level explanatory variables (EVs) included the task regressors for Test, and Test+ trials and rating periods. Contrasts were performed for each trial type in isolation against baseline, with the main contrasts of interest being the two trial types compared against each other.
Two first level analyses were performed: i) standard task analysis, ii) parametric modulation using first level trial-by-trial VAS ratings. For both, a second-level analysis was performed to derive mean brain activity across the group. Cluster significance was inferred at a family-wise error rate corrected threshold of 0.05.
Results:
A two-way repeated measures ANOVA showed that the VAS ratings for the left hand were significantly lower than the right hand, but there were no significant differences in pain ratings between Test and Test+ trials, contrary to the hypothesised behavioural effect (Figure 1.).
When considering the mean response to Test trials, there were significant clusters in bilateral S2 as well as contralateral Cerebellum. Group averaged contrasts between Test and Test+ stimulus classes also indicated significant clusters of stronger BOLD signal in bilateral S2 and contralateral cerebellum (see Figure 2.). Groupwise effects were not maintained in the parametric modulation analysis.
When considering the mean response to Test trials, there were significant clusters in bilateral S2 as well as contralateral Cerebellum. Group averaged contrasts between Test and Test+ stimulus classes also indicated significant clusters of stronger BOLD signal in bilateral S2 and contralateral cerebellum (see Figure 2.). Groupwise effects were not maintained in the parametric modulation analysis.
·Figure 1. VAS ratings for each trial type and hand.
·Figure 2. Significant clusters showing greater BOLD signal during Test+ trials compared to Test trials.
Conclusions:
Despite the application of well-characterised pressure stimuli, we observed no behavioural effect implicating recruitment of the DPMS. While significant differences in BOLD signal between trial types were found, none were in cortical/sub-cortical regions suggested to be involved in descending pain control. Patterns of activity resembled previous reports of brain responses to pressure stimulation [2], which we interpret as more likely reflecting the effects of uni- vs bi-lateral stimulation. Our findings suggest that an experimental design optimised for maximising differences in BOLD activity may not be optimal for investigating the required behavioural effect. Since descending pain controls are an important therapeutic target, our study highlights the importance of paradigm design when it comes to understanding their mechanisms.
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 1
Keywords:
FUNCTIONAL MRI
Pain
Somatosensory
1|2Indicates the priority used for review
Provide references using author date format
[2] Jackson, J. B., et al. (2020), 'Noxious pressure stimulation demonstrates robust, reliable estimates of brain activity and self-reported pain.' Neuroimage, 221, 117178.
[3] Nahman-Averbuch et al. (2022). 'Neural mechanisms underlying the conditioned pain modulation response: a narrative review of neuroimaging studies.' Pain, 10-1097.