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.An extensive body of scientific literature supports the idea that nociception is not always necessary for pain (see  for an accessible review).
Chronic pain is a societal problem: It affects 35.5% of people , exerts a substantial burden both financially  and socially , and according to years lived with disability, it is humanity’s most burdensome health condition .
Despite real advances in our understanding of physiology, genetics, brain function, and comorbidities, how acute pain transitions to chronic pain remains to be elucidated.
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.
Participants were excluded if they were unable to distinguish the two tactor locations from each other (see the section below).
Midprocedure exclusion criteria were 1) thermal pain threshold greater than 50°C, 2) fewer than 75% of high-temperature thermal stimuli (UShigh) rated as painful during the acquisition phase, and 3) more than 25% of low-temperature thermal stimuli (USlow) rated as painful during the acquisition phase (see below for details).One possibility is that associative learning drives this transition [5,6].In an acute pain episode, the simultaneous occurrence of nociceptive and non-nociceptive signaling presents a scenario that is apt to classical conditioning, a form of associative learning that occurs through the repeated presentation of a biologically evocative stimulus (unconditioned stimulus [US], e.g., a nociceptive stimulus) with an initially neutral stimulus (conditioned stimulus [CS], e.g., a tactile stimulus).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.Study information was provided electronically and verbally, and in printed form when preferred by the potential participant.Subjects were screened for exclusion criteria over the telephone or via email, and again on arrival for testing.We hypothesized that subjects would become more sensitive to the CS than to the CS- because of the difference in informational value carried by each.We recruited healthy adult participants using flyers and word of mouth.We hypothesized that pairing of one non-nociceptive somatosensory stimulus (CS ) with painful nociceptive heat (UShigh) and another (CS-) with nonpainful heat (USlow) would result in a lower pain threshold to subsequent trials of heat that were paired with the CS than to trials that were paired with the CS-.Our secondary aim was to investigate whether such pairing would alter subsequent perception of the CS relative to the CS-.