Constitutive cyclo-oxygenase-2 does not contribute to the development of human visceral pain hypersensitivity.
OBJECTIVE
Central sensitisation (CS), contributes to the development and maintenance of gastrointestinal pain hypersensitivity. Constitutive cyclo-oxygenase-2 (COX-2) contributes to central sensitisation in somatic pain hypersensitivity but its role in mediating visceral pain hypersensitivity is unknown. We therefore conducted a study to determine if COX-2 inhibition with Valdecoxib attenuates the development or early maintenance of CS in a validated human oesophageal pain hypersensitivity model.


METHODS
Healthy volunteers were studied in two randomised, double blind, crossover studies in which pain thresholds (PT) to electrical stimulation were assessed in the proximal oesophagus, chest wall and foot, prior to and following a distal oesophageal acid infusion. Protocol 1: Valdecoxib, (40 mg) or matching placebo was given orally for 4 days prior to oesophageal acid infusion. Protocol 2: IV Parecoxib (40 mg) or saline was given 120 min after oesophageal acid infusion.


RESULTS
Valdecoxib did not prevent the induction of secondary allodynia in the proximal oesophagus nor did it attenuate it following its establishment. Chest wall PT fell following oesophageal acid but foot PT remained unchanged; highlighting the development viscero-somatic convergence due to CS. Valdecoxib had no analgesic or anti-hyperalgesic effect on chest wall or foot PT.


CONCLUSIONS
Neither the induction nor initial maintenance of acid induced oesophageal pain hypersensitivity is prevented by Valdecoxib, suggesting that constitutive spinal COX-2 does not contribute to the development or early maintenance of acute visceral central sensitisation.
Willert
Robert P
RP
Gastrointestinal Science Group, Hope Hospital, Salford, UK. rpwillert@yahoo.co.uk
Delaney
Claire
C
Hobson
Anthony R
AR
Thompson
David G
DG
Woolf
Clifford J
CJ
Aziz
Qasim
Q
D000328:Adult; D018592:Cross-Over Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D004947:Esophagus; D005260:Female; D006801:Humans; D006851:Hydrochloric Acid; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017288:Pain Threshold / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014781:Viscera; D000096926:Benzenesulfonamides
D052246:Cyclooxygenase 2 Inhibitors; D006851:Hydrochloric Acid; D007555:Isoxazoles; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C409945:parecoxib