Background & Aims

Understanding pain mechanisms and modulation pathways may provide insight into developing targeted interventions. In humans, it is not feasible to directly measure the central mechanisms and nociplasticity. Quantitative sensory testing (QST) has been widely accepted as indirect assessments of central pain modulation. These QST often include both static (i.e., thresholds) and dynamic (i.e., temporal summation, TS, and/or conditioned pain modulation, CPM) assessment using various modalities (e.g., pressure, punctate, thermal stimuli). TS is used as a measure of pain facilitation, while CPM is a measure of central pain inhibition. Often one or more of these QST assessments are used as indicators for the presence of central sensitizaiton in patient populations. Yet, it is unclear how interchangeable QST may be. Thus, this study aimed was to evaluate correlations and agreement between multiple QST assessments (thresholds, TS, CPM) using multiple modalities (pressure, punctate, and heat).

Methods

Healthy, pain-free adults who completed at least 4 of the previously described QST assessments [1] were included in these analyses. Pain thresholds: pressure pain thresholds (PPT) at the deltoid (shoulder); heat pain thresholds (HPT); TS–heat (Medoc) on the volar forearm; TS–pressure (custom device) on the dorsal forearm; TS–punctate (300g von Frey filament) on wrist dorsum; CPM – heat (HPTs at test stimuli pre- and post- conditioning hand cold water immersion (0 deg C, 1 min); CPM – pressure, using shoulder PPTs as test stimuli; CPM–punctate TS, using TS-punctate as test stimuli. Spearman correlations were assessed for continuous QST variables and Kappa coeficients assessed for dichotomous (presence/absence) of TS and CPM. P < 0.01 set for significance.

Results

A total of 199 participants completed the above QST assessments (N = 165 – 168 for each pairwise comparison due to missing data). Thresholds were moderately inter-correlated (PPT – HPT, rho= .39, p<.001) and weakly to uncorrelated with the dynamic QST assessments: PPTs with TS (rho=-.11 to -.23, p=.13 to .003) and CPM (rho= -.02 to .13, p>.05). Similar results observed for HPTs. TS and CPM were poorly associated (rho = -.09 to –0.13, p>.06) for each noxious threshold stimulus, with the exception of TS and the corresponding CPM using TS test stimuli (rho<-.53,p<.001). Further, TS and CPM across stimuli each showed very weak associations (TS: rho= 0.06 – 0.16, p > 0.04; CPM: rho = .01 – .18, p>.02). Cohen’s kappa statistics were consistently low, k < 0.03, showing poor agreement between noxious modalities for TS and CPM.

Conclusions

QST assessments provide distinct information, with little correlation between tests and poor agreement when dichotomized. TS and CPM involve distinct pathways in the CNS, thus it is not particularly surprising that TS can be independent of CPM. This is consistent with prior findings of distinct phenotypes by modality and QST assessment. [2,3] However, the lack of correlation between modalities for either TS or CPM assessments is less intuitive. Prior studies report mixed findings, both in small cohorts (n=33,35).[4,5] Modality influenced the effect of CPM on subsequent TS, consistent with our results, yet observed no significant interaction (TS by modality). [4] Whereas no correlations between test modalities for CPM are also reported, in line with our results. [5] The current findings suggest that QST modality may also reflect activation of distinct central pathways, infering that each assessment may provide unique insights into central pain modulation.

References

1. Wang D, Merkle SL, Lee JE, Sluka KA, Rakel B, Graven-Nielsen T, Frey-Law LA. Multisensory Sensitivity is Related to Deep-Tissue but Not Cutaneous Pain Sensitivity in Healthy Individuals. J Pain Res. 2020;13:2493-2508.

2. Cruz-Almeida Y, Riley JL, 3rd, Fillingim RB. Experimental pain phenotype profiles in a racially and ethnically diverse sample of healthy adults. Pain Med. 2013;14(11):1708–1718.

3. Frey-Law LA, Bohr NL, Sluka KA, Herr K, Clark CR, Noiseux NO, Callaghan JJ, Zimmerman MB, Rakel BA. Pain sensitivity profiles in patients with advanced knee osteoarthritis. Pain. 2016;157(9):1988-1999.

4. Horn-Hofmann C, Kunz M, Madden M; Schnabel E-L; Lautenbacher. Interactive effects of conditioned pain modulation and temporal summation of pain—the role of stimulus modality. PAIN 2018; 159(12):p 2641-2648.

5. Nahman-Averbuch H, Yarnitsky D, Granovsky Y, Gerber E, Dagul P, Granot M. The role of stimulation parameters on the conditioned pain modulation response. Scand J Pain. 2013;4(1):10-14.

Presenting Author

Laura Frey-Law

Poster Authors

Pujit R Mekala

BS

University of Iowa

Lead Author

Laura Frey Law

PhD

The University of Iowa

Lead Author

Topics

  • Assessment and Diagnosis