Responders and nonresponders to topical capsaicin display distinct temporal summation of pain profiles

Abstract

Introduction: Topical application of capsaicin can produce an ongoing pain state in healthy participants. However, approximately one-third report no pain response (ie, nonresponders), and the reasons for this are poorly understood.

Objectives: In this study, we investigated temporal summation of pain (TSP) profiles, pain ratings and secondary hyperalgesia responses in responders and nonresponders to 1% topical capsaicin cream.

Methods: Assessments were made at baseline and then during an early (ie, 15 minutes) and late (ie, 45 minutes) time points post-capsaicin in 37 healthy participants.

Results: Participants reporting a visual analogue scale (VAS) rating of >50 were defined as responders (n = 24) and those with <50 VAS rating were defined as nonresponders (n = 13). There was a facilitation of TSP during the transition from an early to the late time point post-capsaicin (P<0.001) and the development of secondary hyperalgesia (P<0.05) in the responder group. Nonresponders showed no changes in TSP or secondary hyperalgesia during the early and late time points. There was an association between baseline TSP scores and the later development of a responder or nonresponder phenotype (r = 0.36; P = 0.03). Receiver operating characteristic analysis revealed that baseline TSP works as a good response predictor at an individual level (area under the curve = 0.75).

Conclusion: These data suggest that responders and nonresponders have different facilitatory pain mechanisms. The assessment of TSP may help to identify participants with stronger endogenous pain facilitation who may be more likely to respond to topical capsaicin.

Keywords: Capsaicin; Facilitation; Responder; Temporal summation.

Figure 1.

Experimental protocol. (A) Schematic showing sites of topical capsaicin cream application alongside primary and secondary testing zones. (B) All participants were first familiarised with all testing procedures before baseline responses to single and repeated 256 mN pin prick stimuli were determined. Topical capsaicin (1%, 50 µL) was then ejected onto a 9-mm-diameter clear plastic disc that was placed face-down on the L5 dermatome. Visual analogue scale (VAS) ratings were then recorded every 3 minutes throughout the rest of the protocol. At 15 (ie, early pain-free period) and 45 (ie, ongoing pain period) minutes post-capsaicin application, responses to single and repeated 256-mN pin prick stimuli were remeasured. TSP, temporal summation of pain.

Figure 2.

Development of responder and nonresponder profiles. (A) Changes in ongoing VAS ratings in responders and nonresponders after capsaicin application. Data are expressed as mean ± SEM. (B) Individual data for responders and nonresponders during the late time point post-capsaicin application. Red shaded area = pain; blue shaded area = nonpainful sensation. Red symbols represent responders and blue symbols represent nonresponders. N = 24 responders; N = 13 nonresponders. *P < 0.05. VAS, visual analogue scale.

Figure 3.

Development of secondary mechanical hyperalgesia in responders to topical capsaicin. Capsaicin-induced pain ratings in response to 256-mN pin prick stimulation in area adjacent to the flare response expressed as z-scores. Positive z-scores indicate a gain of function (ie, more sensitive), and negative z-scores indicate a loss of function (ie, less sensitive). N = 24 responders; N = 13 nonresponders. *P < 0.05.

Figure 4.

Changes in TSP in responders and nonresponders to topical capsaicin. TSP changes over time for (A) responders and (B) nonresponders. Early time point = 15 minutes postcapsaicin and late time point = 45 minutes postcapsaicin. N = 24 responders; N = 13 nonresponders; data are expressed as mean with individual data points. ***P < 0.001. ns, nonsignificant; TSP, temporal summation of pain.

Figure 5.

Baseline TSP profiles in responders and nonresponders. (A) Individual data points for baseline TSP scores in responders (red) and nonresponders (blue). (B) Comparison of baseline TSP scores in responders and nonresponders. (C) Point biserial correlation demonstrating an association between higher baseline TSP scores and the later development of a responder phenotype (ie, >50 VAS rating measured during the later time point). (D) Relationship between baseline TSP and TSP in the later time point in responders. N = 24 responders; N = 13 nonresponders. *P < 0.05. TSP, temporal summation of pain.

Figure 6.

Receiver operating characteristic curve for TSP as a response predictor. The plot displays sensitivity (true positive rate) over inversed specificity (false-positive rate). Each edge represents a specific TSP cut-off. Generally, values in the upper left corner of the plot are favourable (high sensitivity with high specificity). A random classification would produce values along the dotted diagonal. TSP, temporal summation of pain.