Background & Aims

Conditioned pain modulation (CPM) reflects the capacity of a remote noxious conditioning stimulus (CS) to modulate a test stimulus (TS). Some people exhibit decreased TS pain (inhibitory) during a CS, others experience greater TS pain (facilitatory) or no change (noCPM)[1,3]. This is paradigm-dependent in healthy individuals (noCPM and facilitatory CPM with heat vs. inhibitory CPM with pressure stimuli)[4]. Previously, we found higher power and slower frequency in the alpha band (8-13 Hz) in those with chronic pain compared to healthy individuals in the dynamic pain connectome (DPC)[5-7]. However, we have not explored alpha power as it relates to behavioural measures reflecting individual variability in healthy individuals. Therefore, this study aims to explore brain-behavioural links underlying CPM in healthy individuals using resting state magnetoencephalography (MEG), with a focus on alpha activity in the key regions of interest (ROIs) in the DPC previously associated with CPM[8,9].

Methods

A total of 68 right-handed healthy individuals (39 females, 29 males) underwent CPM testing using heat TS and CS and a 5-minute resting state MEG scan (Elekta Neuromag TRIUX system). The CPM effect was calculated as a %change in pain intensity evoked by a painful TS on one forearm due to a concurrent painful CS delivered to the other forearm (Qsense, Medoc Inc)[4]. In this study we compared 4 alpha metrics between the 3 CPM groups (facilitatory, inhibitory, and noCPM): total alpha power from the area under the power-frequency curve (AUC alpha power), power at 10 Hz (mid-alpha power), frequency where alpha power peaks (PAF), and power at PAF (PAF power). GraphPad Prism was used for group statistical testing with the Benjamin-Hochberg method at FDR 0.05 used to correct for multiple comparisons across ROIs.

Results

Of the 68 participants, 32% had inhibitory CPM (-37.1% +/- 26.2%; 17 F, 5 M), 49% had facilitatory CPM (26.2% +/- 17.4%; 18 F, 15 M), and 19% had noCPM response (0% +/- 0%; 4 F, 9M). There was no significant age difference between the inhibitory, facilitatory and noCPM groups. The most prominent MEG finding was that the noCPM group had significantly higher mid-alpha, AUC alpha, and PAF power compared to the facilitatory CPM group in the right thalamus, medial prefrontal cortex (mPFC), and dorsolateral prefrontal cortex bilaterally (dlPFC). Right hemispheric differences were strongest (thalamus, dlPFC). Additionally, in the mPFC, the inhibitory CPM group had higher alpha power in all 3 power measures compared to the facilitatory CPM group. There were no significant group differences in PAF that passed multiple comparisons corrections, however PAF in the inhibitory group was negatively correlated with CPM in the right dlPFC and bilateral thalamus.

Conclusions

Our novel finding of alpha power differences between individuals with facilitatory CPM and noCPM highlights the importance of distinguishing these CPM effects, often not done in CPM studies. The greater thalamic and dlPFC alpha power found in the noCPM group may reflect a reduced sensory gating from the thalamus that produces sensory information overflow to the dlPFC of the salience network (SN)[6,10]. Since the SN is engaged when pain is attended to and that distraction strengthens CPM, great attention to pain could act to block CPM[11]. Also, different mPFC alpha activity across CPM groups could reflect the capacity of the descending pathway to modulate pain. Finally, the relationship between weaker inhibitory CPM with slower PAF aligns with other studies in healthy individuals linking pain sensitivity with slower PAF[12]. Thus, brain-CPM relationships were characterized by alpha power in the DPC and relationships between alpha frequency and CPM strength in the inhibitory CPM group.

References

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Presenting Author

Rima El-Sayed

Poster Authors

Rima El-Sayed

BSc

Toronto Western Hospital

Lead Author

E-mail

Joshua Cheng

PhD

University of Toronto and University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Anton Rogachov

PhD

University of Toronto and University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Natalie Osborne

Northshore University HealthSystem

Lead Author

E-mail

Ariana Besik

MSc

University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Vaidhehi Sanmugananthan

BSc

University of Toronto and University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Kasey Hemington

PhD

University of Toronto and University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Junseok Kim

PhD

University of Toronto and University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Rachael Bosma

PhD

University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Emily Mills

PhD

University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Benjamin Dunkley

PhD

University of Toronto and The Hospital for Sick Children, Toronto, ON, Canada

Lead Author

E-mail

Karen Davis

PhD

University of Toronto and University Health Network, Toronto, ON, Canada

Lead Author

E-mail

Topics

  • Pain Imaging