*4.2. Differences in the Association of Fear-Avoidance and Pain Intensity*

The fact that men had a higher mean TSK-score than women in the present study is consistent with the literature from previous cross-sectional studies that investigated sex differences in TSK-scores concerning chronic pain patients [24,25]. It remains debatable why male chronic pain patients tend to have more fear-avoidance than female patients, although it has been suggested that this could depend upon social norms, higher expectations or a deeper concern about losing work capacity or productivity as a result of re-injury [25]. However, the results of our study indicate that the tendency of having more fear-avoidance does not seem to influence pain intensity in men. Moreover, whether the increase in fear-avoidance in men at baseline influences (negatively) pain treatment outcomes remains unanswered.

#### *4.3. Sex Differences in the Association between Fear-Avoidance and Pain Intensity*

Both the unadjusted and adjusted model concerning the interaction between fearavoidance and sex in relation to pain intensity showed that this interaction was significant, and hence, the association between fear avoidance and pain differs between men and women. The adjusted model was corrected for the affective experiences 'relaxed', 'irritated', and 'satisfied', but did not lead to a different conclusion. In the unadjusted and adjusted models, the association between fear-avoidance and pain intensity for men was negligible (0.02 and −0.04, respectively). In contrast, for women, the model demonstrated that the association between fear-avoidance and pain intensity was equal to a coefficient of 0.18 in both models (Table 2), indicating that increases in fear-avoidance were associated with (slight) increases in pain intensity. Whether this (small) association was clinically significant, it may yet be debated. We propose to further investigate if this association holds when applied to other pain populations, preferably with larger sample sizes and equal percentage of both sexes.

Ramirez et al. in 2014 [26] analyzed differences in pain experience between men and women in patients with spinal chronic pain and found a contrasting result, in that fear-avoidance was associated with pain intensity in men, but not in women. However, because of the cross-sectional design of the study the strength of the evidence is limited. Moreover, previous studies suggest that women are more sensitive to threat-related stimuli than men, and this would generally lead to an increased pain perception [6,27] and have greater catastrophic thoughts than men, which would generally lead to an increased pain perception. The results found in the present study are in line with these suggestions.

No previous studies have investigated the potential confounding effect of affective states on the association between fear-avoidance and pain intensity with the ESM. In a review by Baets et al. in 2019 the predictive moderating and mediating roles of emotional factors were examined on pain and disability following shoulder treatment [28]. A predictive role was found for fear-avoidance of pain and disability when surgical treatment was given, yet not when receiving physiotherapy. Moreover, this study indicated a moderating role for optimism in the relationship between catastrophizing and shoulder disability in patients receiving physiotherapy. However, this role was not found in the relationship between fear-avoidance and disability of the shoulder. The results of our ESM study specified that affect has a moderating effect on pain intensity itself, but not on the relationship between fear-avoidance and pain intensity. The statistically significant effect of positive affective experiences, such as feeling relaxed (−0.15, *p* ≤ 0.001) and satisfied (−0.10, *p* ≤ 0.001), on pain intensity itself may indicate that there is a potential role for positive affect, such as optimism, self-efficacy and positive expectations in future research and treatment [28,29].

#### *4.4. Strengths and Limitations*

The present study has a few important advantages. First, due to the use of the ESM, symptoms were assessed in the actual moment, eliminating the potential influence of recall and contextual biases, which is a common problem with traditional retrospective questionnaires [30,31]. Moreover, symptoms such as pain and fear, as well as affect, are likely to fluctuate over time [7]. Due to the many repeated measurements in ESM, these fluctuations could be captured, in contrast to cross-sectional studies. Because of these advantages and the low cost of the ESM method, it might be an attractive and effective method to use more often in future (clinical) studies, or even treatment trajectories, since ESM is feasible due to the widespread use of smartphones. Moreover, ESM may be applied as an additional tool in clinical practice to provide feedback as part of personalized pain intervention [32].

On the other hand, this study has a few limitations. First, seventy-two percent of the participants completed the full 6 days from the ESM examination-period, which resulted in 28% missing data. As experience sampling is time-consuming, these missed assessments were expected beforehand, and the repeating character of ESM accounts for, and decreases, the influence of missing data [33]. However, missed assessments might be a concern, as a sub-group of pain patients might have missed assessments as a consequence of their current mood or level of pain. This may have resulted in overestimation of functioning [9]. Moreover, the sample size in this study was rather small, with an especially low number of men. The percentage of 29% of men deviates from the 40% of men in the overall pain registry cohort DATA*PAIN* [22]. Accordingly, a lack of power could explain why no significant association was found between fear-avoidance and pain intensity for men. Many patients who initially indicated to be interested in the study chose not to participate after receiving all information about the study procedures (Figure 1). This indicates that ESM may be (too) burdensome, at least with the current number of questions and repeated measures. As the usability of ESM in chronic pain patients has not yet been validated, it remains difficult to conclude whether this method is suitable for the chronic pain population. Although momentary assessment is recommended in different somatic and psychiatric conditions, and the benefits of the ESM are becoming more and more apparent [34], it is important to perform more research about ESM and to evaluate its validity and reliability in chronic pain patients.

Fear-avoidance was assessed by the statement 'due to fear for (more) pain I did not make unnecessary movements since the last beep', asking the participant how the behavior of fear has influenced the level of movement since the last beep. As a result, a time frame is assessed between the afore-appointed beep until the actual beep, representing a lagged item. This was the main reason why we did not add a lagged model, as in our case that would be regressing two time points in time instead of one. Moreover, as mentioned before, no intention of causality was intended, meaning that the direction of predictor and outcome could have been reversed: an analysis we want to recommend for future research.

Furthermore, even though the dataset covered a vast number of relevant factors for chronic pain, some factors such as pain etiology were not accounted for at baseline, and other important factors such as pain catastrophizing were missing in the daily assessments, which could explain the sex differences found in our results.
