Stress and visceral pain: From animal models to clinical therapies

Abstract

Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain.

The Irritable Bowel Syndrome: How Stress Can Affect the Amygdala Activity and the Brain-Gut Axis

“…Stress is known to increase visceral sensitivity [ (Larauche, et al 2012) for review]. Either acting at the central and/or peripheral (e.g.…”

“…Brain imaging techniques have shown modulation of brain activation, as for example in the amygdala, by such treatments (Goldin and Gross 2010;Lawrence, et al 2011). Conventional treatment as represented by anti-depressives, anxiolytics, drug targeting the central sensitization syndrome α2δ ligand (pregabalin, gabapentin); tachykinin receptor antagonists either directly and/or indirectly are supposed to target the hyperfunctioning of the amygdala (Ghaith, et al 2010;Gale and Houghton 2011;Trinkley and Nahata 2011;Larauche, et al 2012). In the context of the microbiota-brain-gut axis, probiotics, prebiotics, antibiotics such as rifaximin, an antibacterial agent that is virtually unabsorbed after oral administration and is devoid of systemic side effects, are of interest (Bercik, et al 2011;Fukudo and Kanazawa 2011).…”

Glutamate Transporter Activators as Anti-Nociceptive Agents

“…Studies in other laboratories have corroborated a spinal site of GLT-1 up-regulation to attenuate somatic nociception [20,21]. An important area in the study of functional bowel disorders is role of early stressors mediating adult hyperalgesia [22]. A recent report shows effectiveness of glutamate transporter activator riluzole to mitigate the visceral hypersensitivity caused by premature maternal separation in the rat [23].…”

Modulation of Visceral Pain by Stress: Implications in Irritable Bowel Syndrome

“…Dual visceral pain responses -hyperalgesia and analgesia have been described in rodents. Stress-induced www.intechopen.com hyperalgesia has been examined in detail in several recent reviews (Larauche et al, 2011a;Larauche et al, 2011b; to which the reader is referred to. By contrast, while extensively described in the somatic pain field (Butler & Finn, 2009), to date stress-related activation of descending inhibitory pathways under conditions of visceral pain has received less attention.…”

“…Over the past 15 years, various animal models have been developed to gain a deeper insight into the central and peripheral mechanisms of visceral hypersensitivity (Holschneider et al, 2011;Mayer et al, 2008). However, only recently has the role of alterations in descending pain modulatory pathways in the pathophysiology of IBS and experimental models of IBS been recognized (Berman et al, 2008;Larauche et al, 2011a;Larauche et al, 2011b;WilderSmith et al, 2004). In this chapter, we will review the recent developments on stress-related modulation of visceral sensitivity to colorectal distension (CRD), with a special focus on alterations in stress-induced visceral analgesia and pain inhibitory mechanisms.…”