A simple pain model for the evaluation of analgesic effects of NSAIDs in healthy subjects

Abstract

Aims Non-steroidal anti-inflammatory drugs (NSAIDs) are believed to counteract inflammation and inflammation-induced sensitization of nociceptors by inhibiting peripheral prostaglandin synthesis. We evaluated an experimental pain model for NSAIDs, that included an inflammatory component to mimic clinical inflammatory pain conditions. Methods The study was performed in a randomized, double-blind, placebocontrolled, two-way crossover design on 32 healthy volunteers. A small skin area of the proximal upper leg was irradiated with a UVB source using three times the individually estimated minimal erythema dose. Twenty hours after irradiation skin temperature, heat pain threshold and tolerance in sunburn spot were measured using a thermal sensory testing. These measurements were repeated 2 h after medication of either 800 mg ibuprofen as single oral dose or placebo capsules. Effects of ibuprofen on outcome parameters were assessed with analyses of covariance ( ANCOVA ). Results Placebo did not affect heat pain threshold or tolerance. By contrast, ibuprofen increased heat pain threshold by 1.092 ∞ C [confidence interval (CI) 0.498, 1.695; P = 0.0008) compared with placebo. Heat pain tolerance also increased significantly by 1.618 ∞ C (CI 1.062, 2.175; P = 0.0001). Conclusion The pain model we evaluated was well tolerated in all subjects and the effects of ibuprofen were highly significant. This model is simple, sensitive to NSAIDs' effects and therefore has potential for future experimental pain studies.

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

“…Repetitive pinching of the interdigital web has also been used in trials of ibuprofen and a good effect of the drug in preventing hyperalgesia was found [21,33]. Ultraviolet B (UVB) radiation of the skin promotes hyperalgesia to heat and mechanical hyperalgesia, which was decreased by ibuprofen [33,34]. This model slowly develops a mild skin inflammation producing hyperalgesic mechanisms of peripheral origin [33].…”

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

“…Repetitive pinching of the interdigital web has also been used in trials of ibuprofen; however, results were inconsistent PHARMACOLOGY OF HUMAN PAIN MODELS for this model (Kilo et al, 1995;Petersen et al, 1997). UVB radiation of the skin promotes hyperalgesia to heat and mechanical hyperalgesia, which was decreased by ibuprofen (Bickel et al, 1998;Sycha et al, 2003). The burn injury model has also been applied in the testing of ibuprofen, where pain in response to brushing but not to punctate stimuli was reduced in the secondary hyperalgesic area (Petersen et al, 1997).…”

Pharmacological Functional MRI Assessment of the Effect of Ibuprofen-Arginine in Painful Conditions

“…Each subject received a total single dose of 800 mg (2 sachets of 400 mg each), dissolved in 150 ml of non-sparkling mineral water and administered orally. The dose in a single administration was selected in accordance with previous studies on artificially-induced pain (17)(18). All volunteers underwent electrical stimulation of the median nerve on the right wrist, with an electrical stimulus consisting of a rectangular pulse of 1.9 Hz frequency and 400~s duration, delivered via non-magnetic AgCI electrodes (19)(20).…”