Abstract
Pain is a common, necessary experience modulated by myriad biological and psychological factors and is not a standardised outcome of nociceptor activation. As such, there is large variation in pain sensitivity and expression of endogenous pain modulation observed in laboratory studies on healthy participants. Pain perception is partly driven by activity in the descending pain modulatory system (DPMS). Perception-driven activity in DPMS pathways can be probed using human psychophysics, which allows us to directly study the relationship between physical stimuli and mental phenomena. The studies presented in this thesis explored endogenous modulation of pain and somatosensory function using the psychophysical paradigm conditioned pain modulation (CPM) and a standardised and validated quantitative sensory testing (QST) protocol.In Chapter 1, the reliability of CPM expression was assessed in two samples of healthy participants using thermal and mechanical modalities and a novel, enriched protocol. The major finding of this study was that inhibitory CPM is expressed in a subset of healthy participants irrespective of the stimulus modality used, albeit not reliably. Considerable within-subject and between-subject variation in the effect sizes were reported. Importantly, so-called inhibitory CPM expression was also observed in the absence of any conditioning stimulus. In Chapter 2, CPM expression was assessed in healthy participants using a simplified, novel protocol and test-retest study design. The stimulation parameters and average conditioning pressure used in this CPM study were also used to inform a novel, diffuse noxious inhibitory control (DNIC) electrophysiological study. The results of this study demonstrated inhibitory CPM expression and DNIC activation in the human and rodent studies, respectively, permitting inference that inhibition of spinal wide-dynamic range neurons is occurring at the point of conditioning in humans. Finally, in Chapter 3, a QST study was performed in samples of young people with and without self-harm, living at home or in residential care. The aim of this study was to see whether pain and non-pain sensitivity changed with incidence and frequency of self-harm within the previous year. The results of this study demonstrated a significant dose-response relationship between sensitivity to a wide range of QST stimuli, and incidence and frequency of self-harm.
The studies presented in this thesis extend and build upon previous findings. First, stringent analysis parameters should be in place for estimation of inhibitory CPM since threshold change can occur on its own across test stimulus repeats. In addition, inhibitory CPM may be falsely attributed to the effects of the conditioning stimulus since inhibitory CPM was observed in the sham conditioning sessions. This thesis also provides novel evidence that manual cuff pressure algometry can activate robust DNIC in anesthetised rodents equivalent to that previously reported using validated stimuli. Finally, this thesis provides novel evidence on somatosensory sensitivity in a large dataset of young people with and without self-harm.
The findings suggest that pain sensitivity, as measured by pressure pain threshold, could be used as a biomarker for self-harm and suicide risk in young people living in residential care settings.
| Date of Award | 1 Jun 2023 |
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| Original language | English |
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| Supervisor | Anna Andreou (Supervisor) & Stephen McMahon (Supervisor) |