Ph.D Thesis

Ph.D StudentHonigman Liat
SubjectExploration of Pain Sensitivity Assessment: Assembling a
Multi Dimensional Framework in the Research of
Pain Modulation Profile
DepartmentDepartment of Medicine
Supervisors PROF. David Yarnitsky
DR. Michal Granot
Full Thesis textFull thesis text - English Version


Pain perception is a complex multifaceted process, influenced by a variety of modulatory mechanisms, and affected by physiological and psychological factors. Variability in pain sensitivity is universal, existing in healthy people and pain patients alike. Identifying the features that characterize the individual phenotype on the continuum of pro- to anti-nociception necessitates addressing conceptual and methodological key questions. This dissertation aimed to expand our insights regarding these issues as well as better reveal the underlying mechanisms shaping the individual pain modulation profile (PMP) by encompassing findings from four lines of comprehensive investigation.

The first line of investigation addressed the role of non-painful 'conditioning stimulus' in the descending inhibition obtained by the conditioned pain modulation (CPM) paradigm. The second study focused on methodological challenges and how these affect accuracy of the psychophysical evaluation by exploring the: (i) role of the 'test stimulus' modality on the CPM efficacy,  (ii) the relationships between the ascending and descending pain pathways, and (iii) interplay between the static and dynamic test measures. Based on the accumulative understandings obtained from these projects, the third arm of investigation was conducted to illuminate the complex issue of pain sensitivity evaluation. The course framework for this research included addressing pain inter-variability by incorporating assessment of both the facilitatory and inhibitory pathways, as obtained by multi-modal measurement in order to phenotype healthy individuals. Lastly, the fourth line explored the relative contribution of pain-related psychological features to pain sensitivity evaluation within the context of the pain modulation profile (PMP).

The findings of this project’s first constituent demonstrated that mild mechanical compression attenuates perception of remote experimental pain stimuli; and that this compression-induced analgesia (CIA) response was affected by the stimulation area size; probably mediated by spatial summation. The linkage between CIA and CPM effect may suggest that both share similar inhibitory mechanisms.

The findings of the second study emphasized the distinction and dissimilarities between the various psychophysical measures as demonstrated by absence of association between: (i) CPM efficiencies evoked by thermal and mechanical modalities; (ii) TS and CPM; (iii) static and dynamic QST measures. These findings support the notion that despite involvement of all in the modulatory processing of nociception, each component of this psychophysical 'mosaic' maintains autonomous contribution in characterizing the individual PMP.

The results of the third study emphasized the ability to depict gradient diversity in the pain modulatory processing represented in the psychophysical model. Findings demonstrated that the combined score according to each measure’s sub-grouping may essentially depict the individual’s phenotype, ranged between the pro- to anti-nociception modulation anchors.

The fourth line of investigation highlighted the unique value of the less explored features including memory, imagination, context, and anticipation as crucial cognitive-emotional elements of nociception and clinical pain, depicted by the 'pain sensitivity questionnaire'. The findings validate the contribution of the various psychological characteristics in determining the individual PMP.

This desertion provides new insights allowing the better understanding of pain sensitivity evaluation. Such novel amalgamation obtained by this multi-modal and dimensional design may allow better conceptualization of the individual PMP.