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Background: With medical information widely available, patients often have preconceived ideas regarding diagnostic procedures and management strategies.

Objectives: To investigate whether expectations, such as beliefs about the source of symptoms and knowledge about diagnostic tests, influence pain perception during a clinical diagnostic test.

Design: Cross-sectional study.

Methods: Pain was induced by intramuscular hypertonic saline infusion in the thenar muscles. In line with sample size calculations, fifteen participants were included. All participants received identical background information regarding basic median nerve biomechanics and basic concepts of differential diagnosis via mechanical loading of painful structures. Based on different explanations about the origin of their induced pain, half of the participants believed (correctly) they had ‘muscle pain’ and half believed (incorrectly) they had ‘nerve pain’. Pain intensity and size of the painful area were evaluated in five different positions of the median nerve neurodynamic test (ULNT1 MEDIAN). Data were analysed with two-way analyses of variance.

Results/findings: Changes in pain in the ULNT1 MEDIAN positions were different between the ‘muscle pain’ and ‘nerve pain’ group (p < 0.001). In line with their expectations, the ‘muscle pain’ group demonstrated no changes in pain throughout the test (p > 0.38). In contrast, pain intensity (p ≤ 0.003) and size of the painful area (p ≤ 0.03) increased and decreased in the ‘nerve pain’ group consistent with their expectations and the level of mechanical nerve loading.

Conclusion: Pain perception during a clinical diagnostic test may be substantially influenced by pain anticipation. Moreover, pain was more aligned with beliefs and expectations than with the actual pathobiological process.