It is well known that FMS, an extraintestinal chronic pain disorder characterized by widespread pain, is frequently associated with IBS patients with higher severity of illness [
8,
9]. Importantly, somatic mechanical hyperalgesia is a characteristic feature of so-called "tender points" which are a hallmark of FMS and part of the 1990 classification criteria of the American College of Rheumatology for this syndrome [
7]. There is a large body of evidence for a generalized lowering of somatic pressure pain thresholds in FMS patients [
33,
34], and the mechanical allodynia of FMS patients is not limited to tender points, but appears to be widespread [
35]. In addition, almost all studies of FMS patients have shown abnormalities in pain sensitivity while using different methods of somatic sensory testing. It has been previously demonstrated that IBS patients have somatic hypoalgesia to mechanical stimuli [
10] and the presence of FMS combined with higher severity of IBS influence the perception of somatic stimuli induced by TENS [
14]. Conversely, other studies demonstrated that patients with IBS may also have cutaneous hyperalgesia. Caldarella et al. [
11] found in IBS patients a normal skin sensitivity to electrical stimuli, but lowered pain thresholds at the subcutis and muscle when compared to healthy controls (HC); whereas IBS patients with FMS or patients with FMS alone had significantly lower pain thresholds than HC even at skin level. In another study by Moshiree et al., IBS + FMS patients had enhanced thermal sensitivity compared to IBS only patients during foot immersion in hot water [
13]. Taking these studies together reinforced the concept that IBS patients may also have somatic hypersensitivity depending on the presence of comorbid FM or greater illness severity [
36]. The lack of significant differences in somatic perception between mild and severe IBS patients in this study could be in apparent disagreement with the results of our previous study, in which, however, the presence of FMS could have altered the type of somatosensory perceptual alteration in IBS patients and played a confounding role in the relationships between discomfort thresholds and perception cumulative scores versus IBS severity subgroups [
14]. Moreover, it has been already established that differences in testing procedures and stimulus modalities such as mechanical, electrical, thermal and ischemic stimuli could provoke different results in somatic perception. For example, mechanical stimuli did not reveal any evidence of somatic hypersensitivity in either IBS patients or HC [
10,
37]. Alternatively, there may be subgroups of IBS patients who differ in their somatic sensitivity in response to different stimuli and, interestingly, among subsets of IBS patients with thermal, ischemic, and cold pressor hypersensitivity a minimal overlap between groups was disclosed [
37], suggesting different underlying mechanisms. Less is known about the changes in visceral sensitivity when IBS is associated with FMS. In a previous study IBS and IBS with FMS had significantly lower discomfort thresholds to rectal distention (increased visceral sensitivity) compared to HC, while FMS only patients were normosensitive at the visceral level [
11]. One of the major limitations of this study, as enhanced by the same Authors, was the recruitment of mostly severe IBS patients, according to a higher number of positive tender points that should correspond to a higher level of severity [
8,
9]. Thus, this group of patients is at a more advanced stage of the disease, which includes some preclinical features of FMS. In this study to overcome this limitation we evaluated mild IBS patients and severe IBS patients with or without concomitant FMS selected using the FBDSI to eventually disclose the differences among groups. The FBDSI is a measure primarily of pain reporting and behavior. It demonstrates known groups’ discriminant validity by differentiating IBS non-patients from IBS patients and IBS patients who also have fibromyalgia corresponding to a greater illness severity of IBS [
38]. It has been hypothesized that patients with mild-to-moderate IBS often have more peripherally generated symptoms with gut-based features (i.e., relieved by defecation worse with eating, intermittent, crampy abdominal pain), whereas patients with more severe and painful IBS tend to have more noxious, continuous, and severe symptoms with psychosocial and somatic comorbidities, thus reflecting the greater central nervous system contribution to their illness experience [
38]. Furthermore, this concept applies across various medical conditions, such as fibromyalgia, chronic fatigue syndrome, inflammatory bowel disease, or other chronic pain conditions, so much so that when a condition is severe, it is associated with more symptoms of greater intensity [
38]. Thus, there is a clinical association of severity with psychosocial and medical comorbidities for these functional conditions. It is beyond the scope of this study to investigate on the multiple pathophysiological link between IBS and FMS. For instance, in both diseases, it has been shown that primary and secondary hyperalgesia are maintained by central sensitization, through tonic nociceptive input from peripheral afferents [
39,
40]. In addition, conditioned pain modulation (pain-inhibit-pain mechanisms - CPM) is decreased in both IBS [
15,
16,
41] and FMS [
42‐
44]. Moreover, hyperalgesia is associated with decreased CPM in patients with IBS [
4], which may result from or contribute to central sensitization, and may predispose to the development of other chronic pain syndromes (e.g. IBS leading to FMS). Another possibility is the contribution of psychological factors to altered pain processing in both diseases.
Given this hypothesis, severity in IBS can be seen as a multi-determined concept that integrates peripheral and central biological processes as they affect symptoms.
Limitations of the study
There are several limitations in this study. The first is that discomfort threshold was defined as the first stimulus (electrical stimulus or rectal pressure) that induced a perception score of ≥5. One could argue that these are levels at which only low-threshold mechanoreceptors respond with the possibility of having a ceiling effect in our thresholds data. However there are considerable differences in definitions used for discomfort or pain thresholds among laboratories. Moreover, we performed less biased protocols to make the stimulus unpredictable to the subject [
46] aiming to reduce psychological bias. However, it is well known that IBS patients may be particularly prone to such bias due to hypervigilance and anticipatory anxiety, even though it is to be established if this anxiety is a cause or consequence of increased visceral perception [
47]. Then, the use of standard distension protocols and perception assessment methods in all centres would be desirable.
The second one is the lack of HC to confirm in our patients the expected somatic and visceral hypersensitivity, although the main aim of the study was to evaluate the differences among well selected IBS patients on the basis of illness severity with or without FMS; another limitation is that nearly two-thirds of the study participants were female and no men were present in severe IBS with concomitant FMS. In fact, we were able to enroll a smaller number of patients, only women, with both IBS and FMS due to the known striking prevalence of women in this group [
48]. Nevertheless, the impact of gender and age on somatic and visceral perception was taken into account and we demonstrated that was not significantly relevant on our results. This finding confirms previous studies in which the correlation between symptom severity and rectal sensitivity was similar in male and female patients with IBS [
18]. Interestingly, differences in brain activation have been reported between men and women with IBS [
18,
49,
50], where female patients showed greater activation of regions that could be part of a pain facilitation circuit; whereas male patients showed increased activity in regions that could be involved in pain inhibition. These observations have led some investigators to believe that estrogen is a pronociceptive hormone responsible for the increased pain sensitivity of females. However, this notion has been difficult to prove in women, because the data have generally shown an antinociceptive action of estrogen in both normal females and in those suffering from chronic pain [
51‐
53].
Finally, based on the current design, we were unable to identify the proposed mechanisms that underlie visceral and somatic changes across different IBS severity.