Gut pain and hyperalgesia induced by capsaicin: a human experimental model

Abstract

Human experimental visceral pain models using chemical stimulation are needed for the study of visceral hyperexcitability. Our aim was to stimulate the human gut with chemical activators (capsaicin, glycerol) and measure quantitatively the induced hyperexcitability to painful mechanical gut distension. Ten otherwise healthy subjects with an ileostoma participated. Increasing volumes of capsaicin 50 microg/ml (0.25, 0.5, 0.75, 1.0, 1.5, 2.0, and 3 ml), glycerol (2.5, 5, and 10 ml) or saline (2.5, 5, and 10 ml) intermingled with sham stimuli were randomly applied to the ileum via the stomal opening at three occasions separated by a week. After each application, pain intensity, qualities, and referred pain area were assessed together with the pain threshold to distension of the proximal gut. 'Boring' and 'hot' pain were evoked in all subjects by low doses (median 0.5 ml) of capsaicin. The median pain onset, peak pain, and pain duration were 55, 85, and 420 s, respectively. Referred somatic pain developed around the stomal opening with a correlation between the pain area and pain intensity. After application of capsaicin, significant hyperalgesia was found to distension of the gut (a 28% reduction pressure in pain threshold). No significant manifestations were found after application of glycerol and saline. Application of capsaicin to the human ileum induces pain and mechanical hyperalgesia. Specific activation of nociceptors in the gut mucosa provides new possibilities to study clinical relevant visceral pain mechanisms.

TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation

“…The potential role of TRPV1 in integrating different physical, chemical, and inflammatory signals and the comparatively high number of capsaicin-responsive colon sensory neurons support the relevance of this channel in sensation and visceral nociception. Consistent with these considerations, luminal application of capsaicin or capsaicin injection into the gut wall lowers sensory threshold or triggers pain in humans (Drewes et al, 2003;Schmulson et al, 2003;Lee et al, 2004). Interestingly, prolonged administration of red pepper, which contains capsaicin, improved symptoms in patients with functional dyspepsia (Bortolotti et al, 2002), likely because of neurotoxic effects of persistent TRPV1 stimulation that leads to transient analgesia in experimental models of neuropathic or inflammatory pain (Karai et al, 2004).…”

Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

“…However, dramatic symptom response following capsaicin injection suggests that TRPV1 receptors are indeed present and functional in normal esophageal mucosa and submucosa. Drewes et al 23 demonstrated that capsaicin administration in the ileum (through a stoma) can elicit "burning" and "boring" symptoms. Furthermore, in their studies TRPV1 activation was also found to play a role in the distension-induced visceral hyperalgesia.…”

“…Furthermore, in their studies TRPV1 activation was also found to play a role in the distension-induced visceral hyperalgesia. 23,24 Capsaicin is a specific agonist of TRPV1 and has been extensively used to study the mechanism of somatic pain (intradermal junction). 13,14 While the strength of a human experiment, like ours, is that it allows qualitative and quantitative assessment of pain, it does not allow detailed study of the molecular mechanism.…”

Unravelling the Mystery of Capsaicin: A Tool to Understand and Treat Pain

“…It has been concluded that capsaicin evokes abdominal sensations by stimulation of chemoreceptors and not mechanoreceptors (Schmidt et al, 2004). However, several studies have found reduction in pain thresholds to mechanical, electrical, and thermal stimulation (Gonzalez et al, 1998;Drewes et al, 2003b;Lee et al, 2004;Hammer and Vogelsang, 2007;Olesen et al, 2009;Brock et al, 2010). This indicates that capsaicin must affect a variety of receptors, and sensitization/ desensitization is not necessarily dependent on the quality of receptor activation but more the quantity or duration.…”