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To calibrate or not to calibrate? This question is raised by almost everyone designing an experimental pain study with supra-threshold stimulation. The dilemma is whether to individualize stimulus intensity to the pain threshold / supra-threshold pain level of each participant or whether to provide the noxious stimulus at a fixed intensity so that everyone receives the identical input. Each approach has unique pros and cons which need to be considered to i) accurately design an experiment, ii) enhance statistical inference in the given data and, iii) reduce bias and the influence of confounding factors in the individual study e.g., body composition, differences in energy absorption and previous experience. Individualization requires calibration, a procedure already irritating the nociceptive system but allowing to match the pain level across individuals. It leads to a higher variability of the stimulus intensity, thereby influencing the encoding of “noxiousness” by the central nervous system. Results might be less influenced by statistical phenomena such as ceiling/floor effects and the approach does not seem to rise ethical concerns. On the other hand, applying a fixed (standardized) intensity reduces the problem of intensity encoding leading to a large between-subjects variability in pain responses. Fixed stimulation intensities do not require pre-exposure. It can be proposed that one method is not preferable over another, however the choice depends on the study aim and the desired level of external validity. This paper discusses considerations for choosing the optimal approach for experimental pain studies and provides recommendations for different study designs.

It is yet to be determined why family history of chronic pain is a risk factor for some chronic pain disorders such as migraine. Several biopsychosocial factors may impact this relationship. This study focuses on pain catastrophization, which is a well-established psychosocial influence on the perception of pain. We explored the relationships between pain catastrophizing scores of an adolescent and their parent and the adolescent’s pain modulation capabilities. Thirty-six healthy female adolescents (9-16 years old, mean=12.08) completed a battery of quantitative sensory testing which included mechanical temporal summation and conditioned pain modulation paradigm (test stimulus was pressure pain threshold; conditioning stimulus was foot immersion in cold water [80C]). In addition, both adolescent and their parent completed the pain catastrophizing scale (aPCS and pPCS, respectively). Interestingly, aPCS was not found to be correlated with pPCS (r2=0.010; p=0.561). Neither aPCS nor pPCS were correlated to the pain modulation responses. It is possible PCS has less influence on pain modulation than pain sensitivity in healthy female adolescents. Future studies should examine these relationships in adolescents with chronic pain. Funded by IHS and National Institutes of Health (R01ns129742).

Animal studies suggest that prolactin impacts pain and higher prolactin levels contribute to pain vulnerability in females (Chen et al., 2020). However, other studies found no sex differences in the impact of prolactin on pain (Patil et al., 2013). We hypothesized higher prolactin levels would be related to lower pain thresholds in females but not males. Adolescents (n=23, 13 females, mean age=12.7) completed heat, cold, and pressure pain thresholds (HPT, CPT, PPT) and a blood draw for prolactin levels. Regression models included the psychophysical assessments and sex, age, prolactin, and prolactin*sex interaction. HPT correlated with prolactin (p=0.036) and sex*prolactin interaction (p=0.041). Higher prolactin levels correlated with lower HPT in males (R2=0.532, p=0.016) but not in females (p=0.972). Similarly, CPT correlated with prolactin (p=0.018) and sex*prolactin interaction (p=0.032). Higher prolactin levels were correlated with higher CPT only in males (R2=0.746, p=0.001) but not in females (p=0.772), or to PPT measures in either sex. Prolactin can regulate pain via the transient receptor potential (TRP) channels. However, it is not clear why higher prolactin levels are related to greater pain sensitivity only in adolescent males. Further research is needed to examine these relationships in adults and adolescents at different pubertal stages and menstrual phases. International Headache Society (IHS). International Association for the Study of Pain (IASP).

Puberty marks the onset of pain-related differences in males and females with the latter reporting greater pain sensitivity as age advances. Much of our current knowledge of pediatric pain mechanisms is extrapolated from findings in the adult population. The objective of this study is to identify sex differences in pain sensitivity in healthy adolescents. We present initial findings from our ongoing over-arching project to investigate the effects of puberty on pain sensitivity. Twenty-two adolescents (mean age 12.8±2.0, 10 males) completed the study. Participants completed the Physical Developmental Scale (PDS) to determine their pubertal status. Using the visual analog scale (VAS), participants rated the pain intensity to noxious heat stimuli (44°C) delivered to the forearm and completed a cold pain tolerance task in which they immersed their foot in cold water (8°C). Upon reaching their respective cold-pain tolerance (max 120-seconds), participants used the VAS to rate their pain intensity. A pilot run of pre-specified regression models included heat and cold pain as the dependent variables, and sex, PDS score, age, and sex x PDS interaction as the independent variables. Only sex was significantly correlated with pain ratings of both heat (p=0.004) and cold stimuli (p=0.003). Surprisingly, males compared to females had higher pain ratings for both heat (2.90±1.24 (mean±SD, 95%CI [2.01,3.79] vs. 1.48±1.02, 95%CI [0.83,2.13]) and cold stimuli (5.19±2.04, 95%CI [3.73,6.65] vs. 2.37±2.45, 95%CI [0.89,3.85]). It is not clear why adolescent males are more sensitive to thermal stimuli. Biopsychosocial factors not included in the model might explain the results. The study is funded by the ‘International Association for the Study of Pain' and the ‘International Headache Society' (PI: Nahman-Averbuch, IRB #202109120).

Although psychological factors such as anxiety, depression, and pain catastrophizing are known to influence pain outcomes in chronic pain populations, there are mixed results regarding whether they influence experimental pain outcomes in pain-free individuals. The objectives of this study were to determine the associations between psychological factors and experimental pain outcomes in pain-free adolescents and adults. Relationships between anxiety, depression, and pain catastrophizing and experimental pain outcomes across 8 different studies (total N = 595) were examined in different populations of pain-free adult and adolescent participants. Analyses were conducted with and without controlling for sex, age, and race. Studies were analyzed separately and as part of an aggregate analysis. Individual study analyses resulted in 136 regression models. Of these, only 8 models revealed a significant association between psychological factors and pain outcomes. The significant results were small and likely due to Type 1 error. Controlling for demographic factors had minimal effect on the results. The aggregate analyses revealed weak relationships between anxiety and pressure pain threshold (Fisher’s z = −.10 [−.19, −.01]), anxiety and cold pain intensity ratings (Fisher’s z = .18 [.04, .32]), and pain catastrophizing and pressure pain threshold (Fisher’s z = −.14 [−.26, −.02]). Sample size calculations based on the aggregate analyses indicated that several hundred participants would be required to detect true relationships between these psychological factors and pain measures. The overall negative findings suggest that in pain-free individuals, anxiety, depression, and pain catastrophizing are not meaningfully related to experimental pain outcomes.

Both pain and negative affect (e.g., pain catastrophizing) interrupt and demand attentional resources, which implicates working memory (WM)—the short-term maintenance and manipulation of information. While these factors may not lead to observable WM performance deficits on easy cognitive tasks, an increase in cognitive load (difficulty) may make it more difficult to conserve accuracy. However, few studies have examined pain, pain catastrophizing, and cognitive load concurrently to evaluate their interactive effect on WM. 42 healthy undergraduate students aged 18-22 completed a WM task (n-back) under randomly ordered pain and no-pain thermal stimulation conditions. Participants responded when the current stimulus matched the stimuli presented n positions back in the sequence, with load increasing from n=1 to n=3. Performance was evaluated using hits (correct responses) and false alarms (incorrect responses). Participants also completed the Pain Catastrophizing Scale. Linear mixed effect models were employed to evaluate the interactive effect of pain catastrophizing, experimental pain, and cognitive load on WM performance. We found a significant three-way interaction among pain catastrophizing, pain condition, and cognitive load on false alarms (b = -.12, SE = .047, t = -2.54, p = .012), 95% CI [-.21, -.029]. Under low load, low catastrophizers had fewer false alarms than high catastrophizers under both pain conditions. However, under high load, low catastrophizers had fewer false alarms than high catastrophizers when pain was on, but more false alarms than high catastrophizers when pain was off. Our findings suggest a complex relationship between pain and WM performance, dependent on task difficulty and individual differences in pain catastrophizing. Results suggest that while catastrophizing alone may not consume enough resources to significantly affect accuracy, even under high load, the combination of pain and catastrophizing overwhelms the increased effort needed to maintain performance under high load, leading to decreased accuracy.