The balancing act: endogenous modulation of pain in functional gastrointestinal disorders

Abstract

Functional gastrointestinal disorders (FGIDs) are characterised by visceral pain or discomfort with an unknown cause. There is increasing evidence for abnormal processing of sensory input in FGIDs. Modulation of sensory input occurs at all levels of the nervous system, with a dynamic balance between facilitation and inhibition and close integration with the body's wider homoeostatic control. Cognitive, emotional, autonomic and spinal reflex pathways effectively orchestrate supraspinal and spinal pain modulation, as demonstrated in neurophysiological and brain imaging studies. Endogenous pain modulation has been studied in visceral pain conditions and abnormal regulation has been shown in irritable bowel syndrome (IBS) and functional dyspepsia, as well as other chronic pain syndromes. A majority of patients with IBS have diminished pain inhibition or even pain facilitation compared with healthy controls. Brain imaging during specific activation of endogenous pain modulation demonstrates a fairly consistent functional hub of mainly frontal, limbic and brainstem modulatory regions in healthy humans. Patients with IBS have a different pattern of activation and a correlation between the imaging and sensory changes. Because the modulatory balance of inhibition and facilitation appears to be distributed within the same functional network, future imaging studies of modulation mechanisms should include conditions allowing quantification of inhibitory and facilitatory components. An altered modulatory balance may well be a unifying pathophysiological mechanism in FGID as it can be driven by both top-down (ie, CNS pathology) and bottom-up (ie, peripheral immune activation) influences, but further validation in diverse FGID groups over time is required. Therapeutic manipulation of the modulatory system is possible by both pharmacological and non-pharmacological means.

Widespread Hyperalgesia in Adolescents With Symptoms of Irritable Bowel Syndrome: Results From a Large Population-Based Study

“…40,54 . These central mechanisms may contribute to maintaining and reinforcing abdominal pain in IBS, and possibly contribute to the high prevalence of co-morbid nonabdominal pain.…”

Mechanisms of Stress-induced Visceral Pain

“…[63][64][65][66] In particular, the amygdala has been found to consistently demonstrate altered activation to visceral stimulation in IBS patients. 67 The amygdala is a brain nucleus that is important for the integration of the body's neurophysiologic responses to stress, as well as modulating the perception of anxiety, which is increased in IBS.…”

The Increased Level of Depression and Anxiety in Irritable Bowel Syndrome Patients Compared with Healthy Controls: Systematic Review and Meta-analysis

“…Therefore, the perception of pain is influenced by the emotional mechanism; IBS symptoms can also be affected by the psychological state. 6,7 Treatment directed towards psychiatric conditions can reduce IBS symptoms' severity. 8 Furthermore, psychosocial factors such as the psychological state, individual's traits, and life stress also affect the gut physiology through the brain-gut axis in the biopsychosocial model of IBS.…”