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Pain Medicine: The Official Journal of the American Academy of Pain Medicine logoLink to Pain Medicine: The Official Journal of the American Academy of Pain Medicine
. 2020 Mar 6;21(10):2262–2270. doi: 10.1093/pm/pnaa006

Experimenter- and Infrared Thermography–Derived Measures of Capsaicin-Induced Neurogenic Flare Among Non-Hispanic White and Black Adults

Brook A Fulton 1, Emily F Burton 2, Sabrina Nance 3, Janelle E Letzen 4,✉, Claudia M Campbell 5
PMCID: PMC7593802  PMID: 32142151

Abstract

Objective

Capsaicin is a widely utilized experimental pain stimulus; however, few studies have reported on ethnic differences in pain responses to capsaicin. The present study used infrared thermography to 1) measure differences in capsaicin-induced neurogenic flare between non-Hispanic black (NHB) and non-Hispanic white (NHW) adults and 2) determine the association between neurogenic flare and secondary hyperalgesia.

Methods

Fifty-four participants (NHB N = 28) underwent heat/capsaicin sensitization model procedures. Neurogenic flare was examined using experimenter (i.e., subjective) and thermography (i.e., objective) measurements. A typically nonpainful mechanical punctate probe was used to measure secondary hyperalgesia.

Results

Ethnic groups did not significantly differ in age, sex, marital status, or personal income. Although experimenters rated a significantly wider area of capsaicin-related neurogenic flare among NHW compared with NHB participants (F1, 52 = 8.33, P = 0.006), thermography results showed no differences between groups in neurogenic flares (F1, 52 = 0.01, P = 0.93). Further, although NHB individuals reported greater average pain during the capsaicin procedures compared with NHW individuals (NHB = 58.57 [3.67], NHW = 46.46 [3.81]; F2, 51 = 5.19, P = 0.03), the groups did not differ in secondary hyperalgesia (F2, 51 = 0.03, P = 0.86), and ethnicity did not moderate the association between neurogenic flare and secondary hyperalgesia (F3, 50 = 0.24, P = 0.87).

Conclusions

Findings cautiously support the use of infrared thermography over subjective experimenter report when measuring neurogenic inflammation in diverse samples. However, infrared thermography should not be used as a diagnostic tool for pain, given the lack of association between these factors. Future research is warranted to replicate these findings in a larger and more diverse sample to determine accurate neurogenic inflammation measures across other ethnic minority populations.

Keywords: Flare, Capsaicin, Ethnic Differences, Objective Measurements, Subjective Measurements

Introduction

Capsaicin is one of the most robustly used methods to induce experimental pain in humans [1]. This approach generates cutaneous hyperalgesia and neurogenic inflammation [2], allowing researchers to measure individual differences in neuronal, immune, and vascular mechanisms of pain [3]. It is also thought to act as a surrogate model of neuropathic pain through the transient induction of primary hyperalgesia and allodynia [4,5]. Despite its germaneness, few studies have reported on ethnic differences in responses to capsaicin [6]. This paucity of evidence hinders knowledge about potential mechanisms underlying pain disparities.

Ethnic differences in pain processing have been more commonly assessed through other experimental pain methods, such as thermal and mechanical noxious stimulation. Specifically comparing black and non-Hispanic white (NHW) individuals, black participants consistently show relatively greater experimental pain sensitivity [6–8]. These experimental findings support clinically relevant patterns of pain disparities, such as more severe pain-related symptoms and disability among black individuals. Because pain in black patients continues to be pervasively under- or differentially treated compared with NHW patients [9–13], improved characterization of mechanisms underlying pain disparities is critical.

To the best of our knowledge, only two previous studies have compared capsaicin responses between black and NHW individuals. First, Jourdain and colleagues examined capsaicin-induced facial skin sensitivity among NHW, black, and Asian women [14]. Although they found a trend for higher detection thresholds in black compared with NHW women, the authors concluded that their approach did not elicit consistent pain responses across any ethnic group. Second, Wang and collaborators showed lower reported pain and weaker neurogenic inflammation (i.e., flare) following capsaicin in black individuals compared with NHW, East Asian, and Hispanic peers [15]. These studies importantly examined differences in capsaicin across a variety of ethnicities; however, they were limited by a weak concentration of capsaicin that did not elicit pain [14] and their approach to neurogenic flare measurement [15].

Regarding the latter point, experimenters have often measured the area of neurogenic flare—thought to represent inflammatory-mediated vasodilation contributing to secondary heat hyperalgesia [3]—visually and in individuals with lighter skin pigments. This approach has led to a limited understanding of how capsaicin sequelae translate to individuals with darker skin tones, who are typically from ethnic minority groups. Newer technologies, such as laser Doppler imaging and infrared thermography, provide objective measures of cutaneous reactions to capsaicin. Laser Doppler imaging—used in the study by Wang and colleagues—however, is prone to error at darker skin pigments [16] and measures shorter-lasting physiological changes [3]. Because infrared thermography measures skin temperature, it is possible that this approach is not confounded by pigmentation and would provide a more valid measure of neurogenic flare across ethnic groups.

For these reasons, the current study measured capsaicin-induced neurogenic flare via infrared thermography among healthy non-Hispanic black (NHB) and NHW adults. The study also assessed whether neurogenic flare was associated with secondary hyperalgesia. We hypothesized that 1) subjective, experimenter-derived measures of neurogenic flare would be greater for NHW than NHB individuals, but infrared thermography measurement would be significantly greater among NHB individuals due to greater pain sensitivity; and 2) there would be a significant positive association between objectively measured neurogenic flare and secondary hyperalgesia across the sample that would not be moderated by ethnicity [3].

Methods

The present study is a secondary data analysis from a larger randomized, single-blind, placebo-controlled experimental study focused on ethnic differences in the relationship between mu-opioid receptor binding potential and capsaicin-induced pain responses (R01MD009063) [17]. For the parent study, participants completed two in-person screenings and two counterbalanced positron emission tomography (PET) experimental sessions lasting up to four hours each. The present study, however, only focused on capsaicin-related data (i.e., neurogenic flare, pain ratings) collected during the first screening session (Figure 1). Data from the PET sessions were not examined in the present study, and methods used in those sessions are reported elsewhere [17].

Figure 1.

Figure 1

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The present study is a secondary data analysis of screening session data from a larger parent project. For this screening session, participants completed physiological and psychosocial measures. Additionally, participants underwent one hour of quantitative sensory testing (QST) followed by ∼30 minutes of a capsaicin/heat sensitization protocol, during which neurogenic flare measures and pain intensity ratings were collected. Secondary hyperalgesia testing was completed following the 30-minute period.

Participants

For the parent study, recruitment was conducted via flyers posted in and around the community, online advertisements, and word of mouth. Participants’ ethnic and racial identity was captured by self-report (for demographics, see Table 1). Participants were eligible if they identified their ethnic/racial background as NHB or NHW. Exclusion criteria included reporting a serious medical condition (including sickle cell disease) or central nervous system disorder, significant cognitive impairment, HIV infection, neuroendocrine disorder, seizure disorder, smoking over one pack of cigarettes daily, current alcohol or drug use problems, use of illicit substances, chronic pain syndromes, unmanaged psychiatric conditions, taking opioid analgesics for pain, allergy to capsaicin or opiates, history of respiratory disease (e.g., asthma or chronic obstructive pulmonary disease), PET contraindications, or inability to perceive or tolerate capsaicin procedures (described below). The study was conducted in accordance with the Helsinki Declaration, and the Johns Hopkins Institutional Review Board approved the study’s protocol. All participants underwent the written informed consent process before participating.

Table 1.

Demographic information for NHB and NHW participants

NHB (N = 28) NHW (N = 26) P Value
Age, mean (SD), y 31.54 (12.34) 32.23 (11.47) 0.70
Reported sex, No., % female 13, 45.8 14, 50 0.57
Education, No., % college graduate or above 17, 67.9 19, 69 0.60
Personal income, No., % <$25,000 yearly) 12, 50 14, 57.6 0.67
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Groups did not significantly differ across any demographic criterion.

NHB = non-Hispanic black; NHW = non-Hispanic white.

Screening Sessions

Participants who met eligibility criteria were scheduled for the first in-person screening session. Verbal consent and written informed consent were obtained, and a urine screen was performed to confirm the absence of illicit substances and pregnancy. Participants completed an inventory regarding their health history and several questionnaires related to psychosocial function. Participants then underwent a variety of quantitative sensory testing (QST) measures followed by 30 minutes of capsaicin procedures (described below) to ensure eligibility. Only data and methods related to capsaicin procedures are reported in the present study.

Participants were excluded from further study procedures if they reported negligible levels (i.e., <30) or very high levels (i.e., 100) of capsaicin-induced pain on a 0–100 scale—with 0 being “no pain at all” and 100 being “the most intense pain imaginable”—30 minutes following capsaicin application. These criteria were set to avoid floor and ceiling effects in the parent study. Participants were then scheduled for the second screening session, which included a magnetic resonance imaging scan to exclude participants with contraindications to PET scanning procedures.

Capsaicin Procedures

Capsaicin procedures were conducted similar to previous reports using a heat/capsaicin sensitization model [11,18–22] in a room that had a standardized temperature between 21°C and 23°C. The heat/capsaicin sensitization model combines noninvasive chemical (i.e., capsaicin) and physical (i.e., heat) nociceptor stimulation methods to safely produce sustained hyperalgesia. During the screening session, a thick piece of nonporous dressing was applied to the skin on the nondominant (left) dorsal hand. This dressing was a template for cream application and included an ∼6.25-cm2 hole, used to standardize the area of application, cut into the center of it. About 0.35–0.4 g of a generic, prescription-strength capsaicin cream (10%) was applied inside this area and evenly spread on the skin. The capsaicin cream was stored in a tube and squeezed onto a metal spatula for weighing and application. The participant was in the room while capsaicin procedures were readied.

Tegaderm transparent dressing was then used to cover the area in order to prevent the capsaicin cream from spreading further on the participant’s hand and onto the thermode (3M Health Care, St. Paul, MN, USA). Consistent with the heat/capsaicin sensitization model, a peltier-based thermode (Medoc US, Minneapolis, MN, USA) was placed onto the area of capsaicin and attached securely to the hand with a Velcro strap, so that it rested directly on top of the area of capsaicin throughout the testing session. The thermode held a constant temperature of 40°C during the session, which also helped to ensure that capsaicin-related pain and infrared thermography measures were not confounded by individual differences in basal skin temperature [23]. Pain intensity ratings were collected every five minutes after the application of the cream for 30 minutes. The ratings during the last five minutes of this session were averaged to yield a mean capsaicin-related pain intensity score for each individual. The cream was removed from the skin at the completion of the session.

Flare Measurement Procedures

Infrared Thermography (Objective Measure)

Before capsaicin was applied, an image of the application site was captured by a digital thermal camera (FLIR ThermoVision A40 M, Danderyd, Sweden). Participants placed their hand, palm down, on a 10.5×12-inch foam board with an 8.5×11-inch transparency securely attached. They aligned their middle finger with the top and center of the transparency; then, their hand was traced onto the transparency in order to standardize the location of their hand with the camera. A three-inch magnet was placed next to the hand for a size reference for image subtraction. The FLIR camera was placed on a standard box eight inches above the base. Capsaicin procedures were then conducted as described above. After removal of capsaicin, participants immediately placed their hand back in the same location on the traced transparency. The magnet and camera box were repositioned onto the base, and the postcapsaicin photo was taken. Figure 2 demonstrates infrared thermography images before and after capsaicin application comparing one NHW and one NHB participant.

Figure 2.

Figure 2

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Infrared thermography measurement was taken using a FLIR camera in non-Hispanic black (NHB) and non-Hispanic white (NHW) individuals before and after capsaicin application. Numbers in the upper left corner of each image represent the detected temperature in degrees Celsius over the section of the skin denoted by a crosshair. Brighter hand sections reflect higher skin temperatures, thought to be reflective of greater neurogenic inflammation.

Photos were uploaded and scored using image subtraction techniques within the FLIR software. The three-inch magnet was first measured to provide a size reference for spatial calibration. Then, the precapsaicin image was subtracted from the postcapsaicin image, such that increases in temperature would result in a positive difference. Once subtraction was complete, the dorsal hand (excluding fingers and wrist) was selected using a freehand region of interest (ROI) tool. A freehand, rather than automated, ROI tool was used due to individual differences in hand shapes. Areas where the hands did not identically match in pre- and postcapsaicin photos were excluded. This freehand ROI was repeated two additional times on each template, and then the average score was used in subsequent analyses.

Experimenter-Derived Measure (Subjective Measure)

The experimenter-derived flare measurements were recorded immediately after the FLIR image was taken. The observed area of redness around the site of capsaicin application was traced onto a transparency. The area of flare was later measured in mm2 using a digital planimeter. The measurement was taken three times and averaged for accuracy.

Secondary Hyperalgesia Measurement

In addition to capsaicin-related pain intensity ratings, we also measured secondary hyperalgesia, or increased pain sensitivity to a remote, noninjured site using previously described methods [24,25]. Secondary hyperalgesia was quantified using a typically nonpainful mechanical punctate probe (32-mN force; probe #4 from The Pin Prick set) on a remote area of skin and slowly moving inward to the area of capsaicin. Once the participant indicated that the sensation was painful or associated with a definitive change in sensation (e.g., tenderness, burning), the spot was marked with a felt marker and procedures on that location were stopped. This method was repeated along eight radial arms in 5-mm steps using one-second intervals, creating a border around the area of skin with altered pain sensation. The pattern was traced on a transparency, and distances were calculated as described in the experimenter-derived flare measurement noted above.

Statistical Analyses

We compared ethnic groups on demographic characteristics, capsaicin-related pain intensity, secondary hyperalgesia, and neurogenic flare measures in IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, NY, USA). Age was compared using an independent-samples t test; reported sex, education, and personal income were compared using chi-square tests.

The present study’s first aim was addressed using a one-way multivariate analysis of variance (MANOVA) to examine ethnic differences in flare measurements. The present study’s second aim was addressed using a one-way analysis of covariance (ANCOVA) and moderated multiple regression [26]. First, ethnic differences in reported pain intensity and secondary hyperalgesia associated with the capsaicin administration were measured using individual one-way ANCOVA models that controlled for individual differences in pain catastrophizing (Pain Catastrophizing Scale [PCS] total score). Pain catastrophizing is a cognitive–affective response style that encompasses rumination, helplessness, and worry [27]. We included these scores as a covariate based on previous work showing pain catastrophizing as a mediator of ethnic differences in evoked-pain responses [28] and capsaicin-related hyperalgesia [29]. Second, we used moderated multiple regression to examine the association among ethnicity, flare, and secondary hyperalgesia. This approach involves a hierarchical regression to first test the relationship between predictors (i.e., ethnicity, FLIR measurement) and the dependent variable (i.e., secondary hyperalgesia), as well as the relative improvement in the model with the inclusion of an interaction term (i.e., ethnicity as a dummy-coded variable × FLIR measure).

Results

Participant Demographics

A total of 697 individuals completed phone screening, and 551 were excluded or declined to participate. One hundred forty-six individuals were consented. Of these individuals, 67 were excluded for capsaicin-related pain ratings outside of the criteria range, and groups did not differ in the proportion of individuals excluded for capsaicin-related pain sensitivity (NHB N = 41, NHW N = 26, χ2 = 1.14, P = 0.29) or pain reported at the exclusion criteria time point (i.e., minute 30 of capsaicin-related pain testing; NHB: mean [SD] = 17.49 [29.9]; NHW: mean [SD] = 13.20 [19.90]; t59 = 0.62, P = 0.54). Twenty-five individuals were excluded based on medical and psychosocial criteria, declining to participate in screening procedures, or having unusable FLIR data due to measurement error. In total, data from 54 participants were included in the present study (NHB N = 28). This sample size differs from the sample size reported for the main outcomes of the parent project [17] because (1) the present study did not exclude individuals from analyses based on neuroimaging criteria and 2) the present study excluded individuals with problematic infrared thermography data. Consistent with our recruitment strategy, ethnic groups did not significantly differ in age (t52 = 0.4, P = 0.70), reported sex (χ2 = 0.3, P = 0.57), education (χ2 = 6.45, P = 0.60), or personal income (χ2 = 3.2, P = 0.67). Table 1 shows specific demographic information, and Figure 3 shows the recruitment flowchart for the present study.

Figure 3.

Figure 3

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After determining preliminary eligibility based on phone screening, 146 individuals attended the in-person screening session used to derive data for the present study. At the in-person screening session, 67 individuals were excluded based on capsaicin-related pain ratings, and 25 individuals were excluded for other factors including poor quality of thermography data. Ethnic groups did not differ in the rate of exclusion based on pain ratings. Data from 54 individuals were included in the present analyses.

Aim 1: Experimenter-Derived vs FLIR-Derived Flare Measurement

Figure 4, A and B, shows results from a one-way MANOVA comparing ethnic groups on experimenter and FLIR flare measurements, respectively. There was a large significant effect of ethnicity on the experimenter-derived measure (NHB = 1,860.51 mm2 [228.99], NHW = 2,812.75 mm2 [237.63]; F1, 52 = 8.33, P = 0.01, ηp2 = 0.14), but ethnic groups were equivocal on the capsaicin FLIR measure (NHB = 41.95°C [5.5°C], NHW = 41.2°C [5.7°C]; F1, 52 = 0.01, P = 0.93, ηp2 = 0.00). There was a trend toward a moderating effect of assessor ethnicity on flare ratings based on the participants’ ethnicity (F4, 48 = 2.1, P = 0.16); however, because this analysis was exploratory in nature and we did not have a proper design to test this moderation systematically, we did not further interpret this result.

Figure 4.

Figure 4

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Measures of FLIR-derived flare (A), experimenter-derived flare (B), average capsaicin-related pain intensity ratings (C), and secondary hyperalgesia (D) were compared between non-Hispanic black (NHB) and non-Hispanic white (NHW) individuals. Only experimenter-derived flare and average capsaicin-related pain intensity ratings significantly differed between groups. Experimenters rated NHW individuals to have a larger area of neurogenic flare compared with NHB individuals, whereas NHB participants reported significantly greater average pain intensity compared with NHW individuals.

Aim 2: Relationship Between Neurogenic Flare and Self-Reported Pain

There was a moderate effect for ethnic differences in pain intensity (NHB = 58.57 [3.67], NHW = 46.46 [3.81]; F2, 51 = 5.19, P = 0.03, ηp2 = 0.09), with NHB individuals reporting significantly greater average pain over the capsaicin application period (Figure 4C). However, secondary hyperalgesia did not significantly differ between groups (NHB = 1,522.9 [189.5], NHW = 1,473.66 [196.7]; F2, 51 = 0.03, P = 0.86, ηp2 = 0.001) (Figure 4D). Regarding the association between FLIR-measured neurogenic flare and secondary hyperalgesia, the overall model was nonsignificant (R2 = 0.01, Adj R2 = –0.05, F3, 50 = 0.24, P = 0.87). Neither ethnicity (β = –0.19, P = 0.44) nor FLIR measurements (β = –0.35, P = 0.42) were significantly associated with secondary hyperalgesia. There was no moderation effect (β = 0.34, P = 0.42) (Figure 5A). Similarly, the model using experimenter-derived neurogenic flare measurements was nonsignificant (R2 = 0.12, Adj R2 = 0.06, F3, 50 = 2.18, P = 0.10), and there was no moderation effect (β = 0.1, P = 0.51) (Figure 5B).

Figure 5.

Figure 5

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Ethnicity did not significantly moderate the association between FLIR-derived flare and secondary hyperalgesia (A) or experimenter-derived flare and secondary hyperalgesia (B). Blue markers and lines represent data from non-Hispanic black participants, and green markers and lines represent data from non-Hispanic white participants.

Discussion

In this study, we measured ethnicity-related differences in neurogenic flare via objective infrared thermography and subjective experimenter-derived values. We further examined ethnic differences in capsaicin-induced pain ratings and secondary hyperalgesia, examining the association between the latter and FLIR-derived flare measures. There was a large effect for significantly greater experimenter-derived measured area of flare in NHW compared with NHB participants, which was presumably a function of skin pigmentation differences between ethnic groups. This difference, however, was no longer statistically significant when measured with the FLIR thermal camera, suggesting equivocal inflammation-mediated vasodilation in NHB and NHW individuals in response to capsaicin. Neurogenic flare was not significantly associated with secondary hyperalgesia, however, and ethnicity did not have a moderating effect.

Capsaicin has long been used as a surrogate model of neuropathic pain in laboratory settings to study transiently induced hyperalgesia/allodynia and neurogenic inflammation [4]; however, this work has largely ignored measurement of diverse ethnic group responses. A review of the extant literature identified two previous reports examining ethnic differences in capsaicin-induced pain responses [14,15], and only one of these studies examined differences in neurogenic inflammation [15]. Our results were not consistent with previous findings showing similar capsaicin-induced pain responses in NHB and NHW participants [14] or relatively greater pain sensitivity in NHW individuals [15]. Additionally, our findings contradict laser Doppler results, showing less capsaicin-related reactivity among NHB individuals [15].

Flare has been historically measured subjectively by quantifying the area of observable redness or through technologies like laser Doppler and thermal imaging. Our data support the notion that subjective techniques might be more prone to inaccuracies in participants with darker pigmented skin [15], increasing the potential for undervaluing physiological reactions among these individuals. More recent studies have used objective techniques in measuring capsaicin-induced flare [15,30]; however, most have been conducted in NHW participants or did not disclose participant ethnicity. The present findings suggest that subjective, experimenter-derived neurogenic inflammation measurements are incongruent with objective, thermography-based measures in NHB individuals; future work should consider using the latter technology when measuring ethnic differences. However, it is unclear whether the present null thermography results circumvented limitations of laser Doppler imaging in individuals with darker skin pigmentation [16]. The present methods should be replicated and directly compared with laser Doppler imaging in measuring capsaicin-related ethnic differences.

The present results did not support our second hypothesis, given that we did not find a significant association between neurogenic flare and secondary hyperalgesia. Previous work has shown an association between thermography-measured flare and secondary hyperalgesia in healthy individuals [3,31]. Both of these studies used intradermal capsaicin injection, rather than topical capsaicin, as applied in this study. It is possible that intradermal and topical capsaicin act on different mechanisms [32] and that, for this reason, we were unable to replicate this previously documented association.

The combined findings have potentially important implications. First, experimenters generally measured greater flare area in NHW compared with NHB individuals. In clinical settings, medical evidence (i.e., overt signs) of pain can influence providers’ judgments and clinical decision-making, so that individuals with more evidence are perceived as having greater pain treatment needs and those with less evidence are perceived as having pain attributed to psychogenic causes [33]. Pain conditions in which cutaneous reactions are a common symptom, such as neuropathic pain, might be susceptible to improperly attributed pain. For example, Eiccholz and colleagues found that despite greater pain ratings among black and Hispanic, compared with NHW, patients with neuropathic pain complaints, significantly fewer received a diagnosis of diabetic neuropathy [34]. Assessment of neurogenic inflammation should potentially rely on tools that are not confounded by skin pigmentation. However, the null association between neurogenic flare and secondary hyperalgesia in the present study suggests that this cutaneous response, as measured by infrared thermography, is not a potential pain biomarker. Although our findings support the use of infrared thermography to examine immuno-vascular phenomena, we—as others have cautioned—do not recommend its use as a diagnostic tool for pain, even among ethnically diverse populations [35].

Individuals aiming to measure neurogenic flare responses to capsaicin in a research context should be aware of the disadvantages of objective flare assessments. First, these technologies are more expensive and time-intensive than traditional, experimenter-derived flare measurements, which might be difficult to implement in medical and research centers with limited resources. Second, thermography measures body temperature, so climate and other factors that would influence overall body temperatures (e.g., physical activity immediately before testing) should be controlled for. Third, laser Doppler imaging is error-prone for individuals with darker skin pigments [16] and requires careful calibration.

There are also several limitations in this study. First, we are unable to provide a clear recommendation about the validity of thermography compared with laser Doppler imaging for measurement of neurogenic inflammation. Given that our findings differ from a previous study examining ethnic differences in capsaicin-induced flares, future studies should compare these two methods directly. Second, although we collected serum data, we did not collect relevant immune markers during the session associated with the present capsaicin data (e.g., substance P, CRGP) that would help determine potential ethnic differences in the association between thermography and seroimmune responses. Third, we had a relatively small sample of NHB and NHW participants, which limits the power and generalizability of findings. Finally, the present study included individuals from only two ethnic backgrounds. Future work is needed to better understand how capsaicin-induced flare differs from and relates to pain sensitivity across other ethnic minority populations, such as individuals who identify as Hispanic, Asian, and multiracial.

These preliminary results should be further validated within larger and more diverse samples but may have implications for future work. Although subjective measurement of flares may cost less and use less time and fewer resources, it can also be problematic. Investigators conducting future research should move toward objective measurements of neurogenic inflammation to more accurately capture this area in those with darker skin tones.

Acknowledgements

This study was supported by grants from the National Institutes of Health to Drs. Claudia Campbell (National Institute on Minority Health and Health Disparities; R01MD009063) and Janelle Letzen (National Heart, Lung, and Blood Institute; F32HL143941).

Authors’ Contributions

All authors substantially contributed to the preparation of this manuscript and conceptualization of the reported study aims. BAF/EFB wrote the manuscript with the support of JEL and CMC, and JEL/SN completed data analyses. CMC provided critical feedback in shaping the study aims and data interpretation.

Contributor Information

Brook A Fulton, Department of Psychiatry, Behavioral Medicine Research Lab, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Emily F Burton, Department of Psychiatry, Behavioral Medicine Research Lab, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Sabrina Nance, Department of Psychiatry, Behavioral Medicine Research Lab, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Janelle E Letzen, Department of Psychiatry, Behavioral Medicine Research Lab, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Claudia M Campbell, Department of Psychiatry, Behavioral Medicine Research Lab, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

 

Funding sources: This study was supported by grants from the National Institutes of Health to Drs. Claudia Campbell (R01MD009063) and Janelle Letzen (F32HL143941).

Conflicts of interest: The authors have no conflicts of interest to disclose.

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