An experimental study of viscero-visceral hyperalgesia using an ultrasound-based multimodal sensory testing approach

Abstract

Widespread visceral hypersensitivity and the overlap of symptom complexes observed in functional gastrointestinal disorders may be related to central sensitization and neuroplastic changes. A multimodal and multi-segmental model was developed to evaluate viscero-visceral hyperalgesia induced by experimental esophageal sensitization in healthy volunteers. Twelve healthy subjects were studied using a double-blinded, placebo-controlled design. The sensitivity to mechanical and heat stimulations was assessed in the proximal esophagus, duodenum and rectum before and after perfusion of the distal esophagus with acid or saline. A special-designed probe was used allowing cross-sectional ultrasound imaging during mechanical and heat stimulation of the esophagus and duodenum. Another probe was used for mechanical stimulation of the rectum. The referred somatic pain areas to gut pain stimulations were also assessed. Following acid perfusion 11 of 12 volunteers showed increased sensitivity to one or more stimulation modalities. An overall increased sensitivity to mechanical stretch in the three gut segments was seen (P=0.0001). Posthoc analysis showed that this was mainly due to increased sensitivity in the rectum (P<0.001). No changes were seen to thermal stimulations (all P-values>0.4). The somatic referred pain area to duodenal stimulations increased (P=0.04), while it was unaffected to esophageal and rectal stimulations (P>0.3). The present method demonstrated a new approach to assess multimodal sensitivity to experimental sensitization of the esophagus and related viscero-visceral hyperalgesia. Central mechanisms can explain the remote hyperalgesia to mechanical visceral stimulation and the increase in referred pain areas. The present method may be used to explore pathophysiology and pharmacological interventions in patients with visceral hypersensitivity.

Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis

“…Such sprouting is known to be associated with an increase in the background and evoked activity of these fibers; that is, fibers that develop sprouts become sensitized [17], [18], which contributes to protein extravasation [13]. This increased nociceptive activity in turn produces changes in the excitability of spinal neurons, a phenomenon called central sensitization [19], [20], which can expand from spinal segments where the fibers enter to more remote regions [21]. In other words, the initial neural pathophysiology (sprouting and abnormal nerve activity) triggered by the ectopic growths can, over time, induce central sensitization, leading to chronic pain and co-morbidity [20].…”

Pain and mechanical properties of the rectum in patients with active ulcerative colitis

“…The radii were computed assuming a circular rectal geometry during the distensions: . Because r zero‐pressure often could not be measured directly, it was assessed as the radius at balloon pressure at 1 cm H 2 O in accordance with previous studies using a logarithmic curve fitting of the radius‐pressure relation during the butylscopolamine distensions 24. Finally, circumferential tension was computed according to Laplace's law: …”

Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

“…Viscero-visceral hyperalgesia where, for example, acidification of the esophagus results in widespread changes in the perception of pain from remote organs, such as the rectum, is another complex form of hypersensitivity (Frøkjaer et al, 2005;Brock et al, 2009a). This is probably explained by more than one mechanism, but it is plausible that central sensitization plays an important role.…”

“…Most of the studies on visceral hyperalgesia have demonstrated increased pain in response to one or more modalities after experimentally induced sensitization by chemicals (Sarkar et al, 2001(Sarkar et al, , 2003Drewes et al, 2003a;Hobson et al, 2004;Pedersen et al, 2004;Frøkjaer et al, 2005;Sami et al, 2006;Willert et al, 2007;Brock et al, 2009a).…”