Classical Conditioning Fails to Elicit Allodynia in an Experimental Study with Healthy Humans

Associative learning has been proposed as a mechanism behind the persistence of pain after tissue healing. The simultaneous occurrence of nociceptive and non-nociceptive input during acute injury mimics the pairings thought to drive classical conditioning effects. However, empirical evidence for classically conditioned allodynia is lacking. We aimed to manipulate pain thresholds with a classical conditioning procedure that used non-nociceptive somatosensory stimuli as conditioned stimuli (CS) and nociceptive stimuli as unconditioned stimuli. We also explored the influence of gender, depression, anxiety, negative affect, and pain catastrophizing on the main manipulation.

Thirty-four healthy humans participated in a differential classical conditioning procedure that used vibrotactile stimulations at two different locations as CS. In an acquisition phase, CS+ was paired with painful thermal stimulation, and CS- with nonpainful thermal stimulation. Heat pain threshold was assessed during paired heat-CS trials before and after acquisition. A 2 (time: 1 and 2) x 2 (condition: CS+ and CS-) repeated-measures analysis of variance compared pain thresholds before and after acquisition. Exploratory analyses explored the influence of gender, depression, anxiety, negative affect, and pain catastrophizing. Postexperiment questions investigated participants' awareness of the contingencies employed.

The classical conditioning procedure did not alter pain thresholds. Exploratory analyses did not reveal any influence of individual differences. Thirty of the 34 participants were unaware of the contingencies between stimuli.

The results of this study provide no evidence that allodynia can be induced in healthy humans using a classical conditioning procedure with simultaneous timing.