Background & Aims
Conditioned pain modulation (CPM) is the human equivalent of diffuse noxious inhibitory control (DNIC) which is typically measured using psychophysical approaches (Kennedy et al., 2016). However, these measures currently lack standardisation and fail to provide insight into the mechanisms of CPM. The development of new objective neurophysiological paradigms has the potential to shed light on the top-down mechanisms of CPM in humans. The R2 nociceptive blink reflex (R2 nBR) represents a polysynaptic neural pathway originating from the trigeminal nerve pathway by stimulating the supraorbital nerve above the supraorbital notch (Marin et al., 2015). It is mediated by A-beta and A-delta fibres which project to wide dynamic range neurons in the medulla (Kofler et al., 2023). In this study, we aim to understand how a heterotopic tonic cuff pressure conditioning stimulus can modulate the R2 nBR as a brainstem readout of CPM.
Methods
6 healthy participants (3 male; mean age: 28.66; final expected sample N = 30) were recruited. Blink reflexes were elicited using stimulating electrodes placed over the right supraorbital foramen and electromyography (EMG) responses were recorded from the orbicularis oculi muscle. Stimuli were delivered between 0.8 – 1.9x R2 nBR threshold at baseline which was repeated twice to establish a stable pre-CPM response. This was then repeated alongside a lower limb tonic cuff pressure stimulus delivered at 70% pressure pain tolerance to assess CPM influences over the R2 nBR stimulus response. Pain perception at 0.8x, 1.3x and 1.9x R2 nBR threshold was also recorded using a 0 – 100 numerical rating scale (NRS). Changes in EMG amplitude and NRS pain ratings at the different stimulus intensities and across different conditions will be analysed using separate two-way repeated measures ANOVA with Bonferroni multiple comparison post hoc tests at both preliminary and final sample sizes.
Results
Preliminary analysis of the two baseline stimulus response measures (i.e. pre-CPM) has shown there was a main effect of intensity (F = 3.95; p <0.001; eta2 = 0.26; n = 6), but no overall main effect of condition (i.e. no difference between baseline 1 or 2; F = 2.82; p = 0.15; eta2 = 0.01; n = 6) and no interaction between condition and intensity delivered (F = 1.02; p = 0.44; eta2 = 0.06; n = 6). In line with the increase in EMG stimulus response, there were also higher NRS pain ratings in response to increasing stimulus intensities at each baseline measure with a significant main effect of intensity (F = 11.95, p = 0.002, eta2 = 0.68, n = 6). Further, preliminary observations in the data has indicated both an inhibition (n = 4) and facilitation (n = 2) of the R2 nBR and associated NRS stimulus response function compared to baseline measures following tonic cuff pressure conditioning.
Conclusions
Our current interim findings demonstrate that repeated baseline R2 nBR and associated pain NRS stimulus-response measures are consistent and show evidence of a stable pre-CPM assessment. Interestingly, we found that some participants then show a clear facilitation or inhibition of the R2 nBR which suggests bidirectional CPM responses can be measured from brainstem regions. These data give some early insight into brainstem mechanisms of CPM inhibitors and facilitators in humans, which will be further analysed at our final sample size (n=30). Further mechanistic insight will also be determined by investigating relationships between brainstem R2 nBR readouts of CPM and the battery of other tests conducted as part of the wider study (e.g. conditioned spinal nociceptive withdrawal reflex, heart rate variability, psychometric questionnaires related to pain, anxiety and coping strategies and psychophysical measures of CPM).
References
Kennedy, D. L., Kemp, H. I., Ridout, D., Yarnitsky, D., & Rice, A. S. (2016). Reliability of conditioned pain modulation: a systematic review. Pain, 157(11), 2410-2419.
Kofler, M., Hallett, M., Iannetti, G. D., Versace, V., Ellrich, J., Téllez, M. J., & Valls-Solé, J. (2023). The blink reflex and its modulation–Part 1: Physiological mechanisms. Clinical Neurophysiology.
Marin, J. C., Gantenbein, A. R., Paemeleire, K., Kaube, H., & Goadsby, P. J. (2015). Nociception-specific blink reflex: pharmacology in healthy volunteers. The Journal of Headache and Pain, 16, 1-8.
Presenting Author
Josh Murphy
Poster Authors
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)