This is the first study to demonstrate that the salivary CgA level of IBS subjects is higher than that of normal subjects. We also demonstrated that, after stretching, the CgA level of IBS subjects became comparable with that of normal subjects. CgA is a major soluble protein in adrenal medullary chromaffin granules and adrenergic neurons and is co-released with catecholamines, which are considered to be a good index of sympathetic activity [41
]. In particular, salivary CgA is reported to be a sensitive and substantial marker of psychological stress, which does not respond well to physical stress [15
]. The results of this study suggest that abdominal muscle stretching may improve sympathetic arousal in IBS subjects.
Patients with IBS show more psychiatric disorders and pathologic behavioral patterns than normal subjects [4
]. A correlation between CgA secretion and the depression score was observed in this study. This result suggests a potential mechanism connecting events in the nervous system (central or enteric) with IBS symptoms. Noradrenaline in the brain plays a crucial role in anxiety, and colorectal distention induces noradrenaline release in the hippocampus [44
]. Not only central but also peripheral adrenergic/noradrenergic functions may contribute to the pathophysiology of IBS. Elsenbruch et al. reported that IBS patients demonstrated significantly greater postprandial increases in plasma noradrenaline and systolic blood pressure [45
]. In inflammatory bowel diseases, disturbed adrenergic regulation of interleukin-10 (IL-10) could be part of the mechanism underlying the modulation of disease activity due to psychological stress [46
]. Disturbed autonomic or neuroendocrine modulation of cytokine production, may play a role in the pathogenesis of IBS [9
]. Increased salivary CgA in IBS subjects suggests that IBS subjects have sympathetic arousal due to increased signaling to the gut afferent neurons.
IBS symptoms are generally worsened by stress and often improve with physical exercise and medications affecting serotonin function [47
]. Sugano et al. reported that the skeletal muscle stretching program improved subjective pain scores of the patients with low back pain and that salivary cortisol concentrations were also significantly decreased up to 90 min after exercise [24
]. Exercise may have beneficial effects on IBS symptoms [50
CgA secretion before stretching was negatively correlated with the stress score of normal subjects. Additionally, the anxiety score was reduced after stretching in the normal subjects. Psychological factors influencing symptom reporting have been identified in the constructs of visceral perceptional amplification and alexithymia [51
]. From a psychological viewpoint, IBS may be conceived as an abnormal cognitive processing of emotional stimuli, via verbal responses, and a tendency to perceive somatic stimuli as evidence of symptoms of disease.
Ghoncheh et al. examined the psychological and physical effect of passive muscle stretching and yoga stretching exercises for relaxation [22
]. Muscle relaxation displayed higher levels of relaxation states, physical relaxation, disengagement and higher levels of joy as a post-training effect [52
]. Muscle stretching provides sensation contrasts for learning relaxation in addition to fostering relaxation through the stretching of muscles [53
]. Muscle stretching for patients with IBS may be of benefit to the patients and could be used as part of a multi-component approach to the treatment of IBS.
Evidence of a physiological component of IBS is based on gender differences in GI symptoms, central nervous system pain processing, and specific effects of estrogen and progesterone on gut function [54
]. Additional factors may play a role, including gender-related differences in neuroendocrine, S/A system, and stress reactivity, which are related to bowel function and pain. Although gender differences in the therapeutic benefits of serotonergic agents have been observed [56
], less is known about potential differences in responsiveness to non-drug therapies for IBS. Multiple comparisons between CgA and gender related information suggest that stretch intervention may have gender dependent effects on IBS.
The following three points can be cited as limitations of this study. The first is that sample size was very small. The levels of CgA found in our subjects were somewhat different from the reported mean value [39
], and our findings could not exclude the effect of the sample size. Additionally, we could not examine the effects on subtypes of IBS (i.e. constipation-predominant or diarrhea-predominant), because the sample sizes of the subtypes were too small to analyze them separately. However, a long follow-up study [57
] proved the inconsistency of IBS subtypes, suggesting that whole IBS analysis is more important than subtype analysis. The second limitation is that the duration of muscle stretching might be too short. The duration of the effect of contraction-relaxation stretching on range of motion (ROM) in the lower extremities is 15 min and the increase in ROM usually remains for 90 min [58
]. Proprioceptive neuromuscular facilitation (PNF) stretching techniques produced greater increases in ROM than static or dynamic stretching exercises. The stretching hold time at the hip is 3–10 sec in one hold-relax PNF stretch [59
]. There is no study that clarifies the stretch duration required of the abdominal muscle for relaxation. Thus, it will be necessary to examine how long we should stretch the abdominal muscles for IBS treatment. Lastly, we could not analyze the effect of lifestyle and medical history on CgA in this study. Many stress-related biomarkers are affected by lifestyle or medical history [60
]. Such relationships might contribute to increased knowledge about strategies to prevent progression of IBS.