Impact of respiration on abdominal pain thresholds in healthy subjects – A pilot study

1 Introduction

The quantification of pain is an essential part of a physician’s daily practice and is crucial for both diagnostic and monitoring purposes [1]. Although unidimensional self-report scales such as the numeric rating scale (NRS) and the visual analogue scale are widely used, they have limitations. For example, these scales are influenced by patients’ mood and previous pain experiences, which can introduce bias into evaluations [2,3,4]. In contrast, pressure algometry (PA) provides an objective quantitative evaluation of pain sensitivity, complementing self-reported assessments. Algometry refers to methods that quantify pain thresholds (PT) by applying controlled pressure to tissues until pain is elicited [5]. It has proven valuable for diagnosing and evaluating the treatment of various conditions: lower back pain [6], neck pain [7,8], chronic pelvic pain [9], patellar tendinopathy [10], knee osteoarthritis [11], and Achilles tendinitis [12], as well as non-orthopedic disorders, such as fibromyalgia [13,14,15], dysmenorrhea [16], and endometriosis [17]. In addition to assessments of superficial tissues, studies focused on the pain sensitivity of deep somatic [18] and visceral afferents [9]. In a retrospective study involving over 400 children with suspected appendicitis, PA demonstrated diagnostic accuracy that exceeded many published clinical algorithms and was comparable to the precision of ultrasound findings [19]. However, the reliability of abdominal PT determination has not been extensively studied, with few investigations to date [2,9]. One aspect that might contribute to the variability of abdominal PT is the activation of the sympathetic nervous system by different phases of respiration (further referred to as the respiration phase), which is particularly strong at low respiratory frequencies (0.1 Hz). It has been shown that pain and pain-related brain activity may be reduced during inhalation [20], which may be at least in part linked to activity of the autonomic nervous system. We therefore explored the impact of varying respiratory positions on the assessment of abdominal PT, aiming to identify sources of variability and thereby increase intrarater reliability of abdominal PT measurements, and to investigate a possible respiration-driven modulation of pain sensitivity.

2 Methods

This study was approved by the local Research Ethics Committee (EK 2021-604). The observational study was registered in the German Clinical Trials Register (DRKS00032288). Prior to enrolment in the study, all participants gave their informed consent both verbally and in writing. Data collection for the study took place entirely on a single day at the medical university’s facilities, with no follow-up conducted thereafter. A total of 31 participants were enrolled, with sampling conducted sequentially over the course of that day. The study design and reporting adhered to the STROBE guidelines, ensuring comprehensive and transparent presentation of observational data [21].

2.2 Procedure

Participants were instructed to lie down in a slightly supine position. Participants were instructed to breathe normally (self-paced) during the assessments, with no external respiratory pacing or monitoring. Six specific abdominal acupuncture points (Figure 1) were manually palpated to identify the most sensitive point for further examination. These points are according to Traditional Chinese Theories situated in areas relevant to gastrointestinal movement and digestion [22,23].

Figure 1

Location of abdominal pressure points and their location on acupuncture points: G1: stomach 25; G2: conception vessel 12; G3: conception vessel 14; G4: gallbladder 24; G5: conception vessel 16; G6: spleen 21. Figure created by the authors using © Freepik (Premium License) resources, modified for the purposes of this study.

To ensure exact forces applied in the measurement of the PT, a force gauge (PCE-instruments FM-200) with a 1 cm² tip was used. The force at the designated point was gradually increased until participants experienced pain rather than just a sensation of pressure. This turning point was defined as the PT, ensuring an objective pain measurement [1].

This process was repeated three times for each participant and respiration phase (inhalation and exhalation). The average of three values was obtained. Each set of three PT trials for a given respiratory phase required only a few minutes to complete, so that, with the 15-min break between phases, the overall testing session for each participant lasted approximately 30 min.

A real-time force–time diagram was displayed on the screen to visually guide the examiner in maintaining this pressure application rate (PAR), thus reducing variability in the pressure application.

The assessment of the PT was conducted in an alternating manner between the two respiration phases (inhalation and exhalation). After the initial measurement, a 15-min resting period was provided before proceeding with the PT evaluation in the remaining respiration phase. Respiratory phase assessments alternated to prevent order effects.

During the inspiratory PT assessment, pressure application ceased when participants needed to exhale. Each PT measurement lasted only a few seconds and was thus completed within a few breathing cycles. Similarly, for expiratory PT measurements, pressure application ceased when participants needed to inhale. This approach ensured that the assessments aligned with the respective respiratory phases for accuracy and reproducibility. Participants naturally pause briefly at the end of each inspiratory and expiratory phase; in this study, these transition pauses were treated as part of the preceding respiratory phase and did not affect the measurement protocol. All measurements were performed by a single examiner to eliminate inter-rater bias. To minimize expectation bias, participants were instructed only to report when they first experienced pain during the pressure application under different respiration conditions. They were not informed about the specific hypothesis regarding the effects of the respiration phase on pain perception. For example, participants were not told that inhalation was expected to produce higher PT; this blinding of the hypothesis aimed to reduce expectation bias in their pain reports.

3 Results

A total number of 31 medical students were included in this study. Basic characteristics are shown in Table 1. The Fisher’s exact test revealed no significant difference in the distribution of the most sensitive abdominal pressure points between sexes (p = 1.0, Table 2).

Three measurements were performed during inhalation and exhalation. The findings revealed a consistent and significant difference in the PT between the two phases. PT was higher during inhalation than during exhalation (492 ± 186 vs 492 ± 186 kPa, p = 0.0003; Table 3, Figure 2).

Figure 2

PT during inhalation and exhalation for each measurement. Significant differences were observed for each value (red: Inhalation; blue: Exhalation).

Interestingly, the first measurement, regardless of whether it was during inhalation or exhalation, yielded the highest PT values. The ANOVA for repeated measurements slightly failed to reach statistical significance (p = 0.0853) for measurements taken during inhalation. The largest difference was found between measurements 1 and 3 (p = 0.0896 after Scheffé’s adjustment). This suggests that PT values tended to decrease over the course of repeated measurements during inhalation. In contrast, the ANOVA for expiratory measurements showed no significant differences (p = 0.6553), indicating that PT values remained stable. Based on the ICC assessments, the reliability of the three measurements obtained during exhalation and inhalation was rather high (ICC = 0.8927 and ICC = 0.8718, respectively). According to Altman and Bland, these values indicate a high level of reliability [25].

Moreover, our findings revealed that sex exerted no impact on PT, with no noteworthy variations observed in any of the measurements. The p-values range from 0.4993 to 0.7438 (Figure 3).

Figure 3

Sex-specific PT: Female (blue) and male (green). No difference in PT was observed between the sexes.

4 Discussion

Algometry is considered an objective stimulation method for assessing PT and is a valuable tool for diagnosing and evaluating the effectiveness of treatments for various disorders [5]. By utilizing PA, researchers and clinicians can obtain more standardized and reproducible measurements of pain sensitivity, thereby reducing the impact of subjective bias. In this study, we found that respiration modulates the abdominal PT and thus needs to be considered in the standardized measurement.

The reliability of PA has been shown in various studies, as described above. The correlation between self-reported instruments for pain assessment (e.g., NRS or VRS) and PT evaluation was described as moderate [26,27] to high [5].

Our findings revealed a significant decrease in PT during exhalation compared to inhalation, indicating a notable reduction in pain perception during the inspiratory phase. This phase is associated with a higher sympathetic tone, while the expiratory phase is characterized by predominant vagal tone [28]. Arsenault et al. highlighted two potential mechanisms for the decreased pain perception during inhalation: one involves central mechanisms during inhalation rather than exhalation. Another explanation worth considering is the distraction effect (i.e., reduced pain perception due to attentional shift away from the pain stimulus) attributed to cued respiration [20]. Additionally, the increased resistance of the abdominal muscles during exhalation [29] may contribute to a shift in the perception of pain. Reyes del Paso et. al. postulated that breath-holding after deep inhalation might reduce pain perception due to the activation of baroreceptors [30]. They only compared pain perception under two conditions: breath-holding after deep and slow inhalation. Nevertheless, this mechanism could also be relevant for this study.

One might argue that intra-abdominal pressure rises with diaphragmatic contraction during inhalation [31]. An external pressure increase during inhalation could further elevate intra-abdominal pressure within the abdominal cavity, potentially leading to a lower PT. However, contrary to this expectation, we observed a higher PT during inhalation, suggesting that increased intra-abdominal pressure alone does not explain this finding.

A possible explanation for the observed differences in PT values between respiratory phases may lie in the variation of PAR, as differences in PAR can influence pain perception and threshold assessments. The PAR used in previous studies varies from 0.05 to 20 N/s [32]. It has been noted that faster rates may lead to false-low threshold evaluations [33,34]. Although the PAR was slightly higher during inhalation, the absolute difference remained below 20 kPa/s and is unlikely to account for the observed difference in pressure PT. In areas like the abdomen, where PT can be higher, a very low rate of 0.63 kPa/s (equivalent to 0.05 N/s when using a 1 cm² algometer tip) may be clinically impractical, as each measurement could become very time-consuming; for instance, assessing a PT of 450 kPa would require approximately 13 min. One way to mitigate potential inaccuracies is to repeat measurements.

Nevertheless, the PT assessment for both respiration phases revealed a high ICC value, indicating high reliability of the data.

In the research conducted by Chesterton and colleagues [35], they observed a sex-based disparity in the assessment of PT at the first interosseous muscle. The present study did not exhibit this sex-specific distinction.

All measurements were performed by the same examiner to ensure consistency in the evaluation process. Additionally, each participant underwent both inhalation and exhalation measurements, providing a direct comparison of pain sensitivity under different respiratory conditions. Given the slightly higher reliability observed during expiration, we suggest that future studies standardize abdominal pressure threshold assessments to a single respiratory phase, preferably expiration. It is important to consistently consider the breathing position during testing and avoid conducting measurements across different respiratory phases within the same protocol. However, our study employed a small sample size and concentrated solely on healthy young individuals. Additionally, the respiratory phase was assessed solely through observation. To achieve more precise control over the respiratory state, the use of a respiratory monitor may be necessary. Further research is needed to confirm this phenomenon in a more diverse and generalized population. Interrater reliability needs to be explored in subsequent studies, with due consideration given to the participant’s respiration phase.

5 Conclusion

Our findings indicate that standardizing respiration phase is crucial for obtaining reliable measurements of abdominal PT, as it may significantly influence pain sensitivity. This modulation may stem from the activation patterns of the autonomic nervous system or variations in muscle tone. These insights are important for developing clinical and research protocols that improve the reliability of abdominal pain assessments.