Background & Aims

Learning to avoid harm is crucial for survival, with pain-related stimuli capturing attention and eliciting anticipatory responses [1,2]. Tonic painful injuries may result in altered spatial perception and distinct responses to looming threats [3]; however, little is known about the neural processes underlying pain anticipation after injury. This study investigates neurophysiological anticipatory responses to pain-related cues in the presence and absence of tonic pain.

Methods

Using a novel multisensory approach, twenty-six healthy participants viewed a dynamic forest scene with a head-mounted display. Animated cues differentiated by colour were followed by an audio-visual stimulus looming towards the left or right side of the body or the ground. During conditioning, left and right looming objects were accompanied by electrical pain stimuli on the corresponding forearm. During extinction, pressure cuffs were inflated to deliver lateralized tonic pain to the upper arm, and phasic electrical pain was not delivered. EEG power spectral changes (event-related desynchronisation and synchronisation, ERD/ERS) [4,5] following the cue were monitored alongside virtual-reality eye-tracking data. Linear mixed-effects models assessed differences in eye-tracking and EEG alpha-band power spectra for pain-predictive versus neutral cues during conditioning and extinction, and for pain-predictive cues congruent versus incongruent to tonic pain during extinction.

Results

Distinct neurophysiological responses emerged during conditioning, with augmented central and parietal alpha ERD following pain-related versus neutral cues. Additionally, looming objects following pain-related versus neutral cues were accompanied by greater pupil diameter. Tonic pain laterality influenced cortical activation changes during extinction, with stronger parietal and occipital alpha ERD for congruent versus incongruent pain-related cues. This effect did not modulate pupil responses. Combined, these findings suggest changes in attention and sensorimotor activation during phasic pain anticipation. Additionally, heightened spatial attention and sensory processing are preserved during extinction when previously pain-predictive cues are congruent with tonic pain location.

Conclusions

In conclusion, our study unveils enhanced anticipatory responses to pain-predictive cues, as indicated by pupil diameter dilation and cortical oscillatory changes in the alpha band. Tonic pain laterality exhibits a top-down attentional effect on cortical oscillatory changes in the alpha band. This novel multisensory method provides insights into pain learning during tonic pain, with potential implications for understanding the transition from acute post-injury pain to chronic pain.

References

1.Atlas LY. How Instructions, Learning, and Expectations Shape Pain and Neurobiological Responses. Annu Rev Neurosci. 2023;46(1). doi:10.1146/annurev-neuro-101822-122427
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3.Hall J, Llewellyn A, Palmer S, Rowett-Harris J, Atkins RM, McCabe CS. Sensorimotor dysfunction after limb fracture – An exploratory study. European Journal of Pain (United Kingdom). 2016;20(9):1402-1412. doi:10.1002/ejp.863
4.Pfurtscheller G, Aranibar A. Event-related cortical desynchronization detected by power measurements of scalp EEG. Electroencephalogr Clin Neurophysiol. 1977;42(6):817-826. doi:10.1016/0013-4694(77)90235-8
5.Pfurtscheller G, Lopes da Silva FH. Event-related EEG/MEG synchronization and desynchronization: basic principles. Clinical Neurophysiology. 1999;110(11):1842-1857. doi:10.1016/S1388-2457(99)00141-8
6.Schlitt F, Schmidt K, Merz CJ, et al. Impaired pain-related threat and safety learning in patients with chronic back pain. Pain. 2022;163(8):1560-1570. doi:10.1097/j.pain.0000000000002544
7.Vlaeyen JWS. Learning to predict and control harmful events. Pain. 2015;156(Supplement 1):S86-S93. doi:10.1097/j.pain.0000000000000107
8.Seymour B, Crook RJ, Chen ZS. Post-injury pain and behaviour: a control theory perspective. Nat Rev Neurosci. 2023;24(6):378-392. doi:10.1038/s41583-023-00699-5

Presenting Author

Danielle Hewitt

Poster Authors

Danielle Hewitt

PhD

Wellcome Centre for Integrative Neuroimaging, University of Oxford

Lead Author

Shuangyi Tong

BMath

University of Oxford

Lead Author

Sarah Schreiber

BSc

University of Oxford

Lead Author

Ben Seymour

BSc MB ChB PhD MRCP FRSA

University of Oxford

Lead Author

Topics

  • Models: Acute Pain