Central pain mechanisms following combined acid and capsaicin perfusion of the human oesophagus.
Visceral afferents originating from different gut-segments converge at the spinal level. We hypothesized that chemically-induced hyperalgesia in the oesophagus could provoke widespread visceral hypersensitivity and also influence descending modulatory pain pathways. Fifteen healthy volunteers were studied at baseline, 30, 60 and 90 min after randomized perfusion of the distal oesophagus with either saline or 180 ml 0.1M HCl+2mg capsaicin. Electro-stimulation of the oesophagus, 8 cm proximal to the perfusion site, rectosigmoid electrical stimulation and rectal mechanical and heat stimulations were used. Evoked brain potentials were recorded after electrical stimulations before and after oesophageal perfusion. After the perfusion, rectal hyperalgesia to heat (P<0.01, 37%) and mechanical (P=0.01, 11%) stimulations were demonstrated. In contrast, hypoalgesia to electro-stimulation was observed in both the oesophagus (P<0.03, 23%) and the sigmoid colon (P<0.001, 18%). Referred pain areas to electro-stimulation in oesophagus were reduced by 13% after perfusion (P=0.01). Evoked brain potentials to rectosigmoid stimulations showed decreased latencies and amplitudes of P1, N1 and P2 (P<0.05), whereas oesophagus-evoked brain potentials were unaffected after perfusion. In conclusion, modality-specific hyperalgesia was demonstrated in the lower gut following chemical sensitization of the oesophagus, reflecting widespread central hyperexcitability. Conversely, hypoalgesia to electrical stimulation, decreases in referred pain and latencies of evoked brain potentials was seen. This outcome may reflect a counterbalancing activation of descending inhibitory pathways. As these findings are also seen in the clinical setting, the model may be usable for future basic and pharmacological studies.
Brock
Christina
C
Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Denmark.
Andresen
Trine
T
Frøkjaer
Jens Brøndum
JB
Gale
Jeremy
J
Olesen
Anne Estrup
AE
Arendt-Nielsen
Lars
L
Drewes
Asbjørn Mohr
AM
D000328:Adult; D000704:Analysis of Variance; D001831:Body Temperature; D002211:Capsaicin / Q000008:administration & dosage*; D002540:Cerebral Cortex / Q000503:physiopathology*; D004558:Electric Stimulation; D004569:Electroencephalography; D004947:Esophagus / Q000187:drug effects / Q000503:physiopathology*; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005260:Female; D006801:Humans; D006851:Hydrochloric Acid / Q000008:administration & dosage*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D012007:Rectum / Q000187:drug effects / Q000503:physiopathology
D006851:Hydrochloric Acid; D002211:Capsaicin