Evidence of Heat Hyperalgesia in Irritable Bowel Syndrome Evidence from Human Irritable Bowel Syndrome Patients

The first study to show large magnitudes of heat hyperalgesia in IBS patients compared VAS ratings of pain intensity and unpleasantness in response to rectal distension and cutaneous thermal stimuli in 12 patients with IBS but without fibromyalgia and in 17 healthy controls (40). Using methods similar to those of other investigators (41,42), phasic distension of the rectum (870 mL/min) to constant pressure plateaus of 35 and 55 mmHg for 30 seconds each were performed, followed by a 60-second interstimulus rest at a resting pressure of 5 mmHg. Cutaneous (heat) sensitivity was tested by asking each subject to immerse his/her right hand (up to the level of the wrist) or right foot (up to the level of the right malleolus) in a circulating, heated, water bath at random temperatures of 45° C and 47° C for 20 seconds each with a five-minute rest between each stimulus.

Similar to previous studies (41,42,45), Verne et al. showed increased visceral perception to phasic rectal distension in IBS patients as compared with control (40). IBS patients rated both rectal distension pressures (35 and 55 mmHg) as more intense and unpleasant compared with controls (Fig. 3, left panel). These same IBS patients also rated cutaneous heat pain in the foot as much more intense and unpleasant in comparison to control subjects, thereby demonstrating secondary cutaneous heat hyperalgesia (Fig. 3, right panel). Heat hyperalgesia also was present in the hand of these patients (Fig. 3, right panel).

A limitation of this study, however, is that all the subjects were female. Thus, it is possible that cutaneous heat hyperalgesia may not be representative of other IBS populations. This limitation was explicitly addressed in a second study of male IBS patients who were veterans that had Gulf War syndrome, a very different population than those of the first study (49). Using the same experimental methodology and experimental design (e.g., ratings of male patients were statistically compared to male control subjects of similar age), this study demonstrated large magnitudes of both visceral and cutaneous heat hyperalgesia. Similar to female IBS patients, heat hyperalgesia was present in both the foot and the hand. Studies of female and male IBS patients were followed by a third study of IBS patients, including both male and female subjects, whose brains were scanned with functional magnetic resonance imaging (52). In comparison to age- and sex-matched control subjects, IBS patients had both visceral and cutaneous heat hyperalgesia that was accompanied by corresponding increased activation of brain regions involved in pain processing, including thalamus, somatosensory areas 1 and 2, insular cortex, anterior cingulate cortex, and prefrontal cortical areas (52). Thus, IBS patients had increased pain-related activation within an entire network of brain areas, including those involved in early levels of afferent processing such as the thalamus (52). In all three studies, the cutaneous hyperalgesia was pronounced in the lower extremity (foot), yet present in the upper extremity (hand) to a lesser extent (40,49,51). In combination, these results suggest that patients with IBS have visceral hyperalgesia and secondary cutaneous hyperalgesia that is distributed over widespread regions of the body, yet optimally expressed in lumbosacral der-matomes. This conclusion is further supported by observations that many IBS patients exhibit a number of extraintestinal pain symptoms such as back pain, migraine headaches, heartburn, dyspareunia, and muscle pain consistent with central hyperalgesic mechanisms (53,54). Similar to other pain conditions that likely depend on peripheral impulse input, such as CRPS, postherpetic neuralgia, and fibromyalgia, IBS patients may develop widely distributed hyper-algesia, possibly related to chronic peripheral nociceptive input from the rectum and colon.

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