A close relationship between anxiety and pain has been demonstrated in different conditions. The nocebo effect, whereby a verbal stressor is capable of inducing hyperalgesia, has been shown to be a good model to study such a relationship. In particular, nocebo hyperalgesia has been found to be associated to the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and benzodiazepines can antagonize both nocebo hyperalgesia and HPA hyperactivity, thus suggesting that anxiety play a major role. Here we investigate how stressful stimuli can modulate pain.

As a stressor, we used a nocebo procedure whereby verbal suggestions of hyperalgesia were given to healthy volunteers before administration of either tactile or low-intensity painful stimuli. Pain perception was assessed by means of a Numerical Rating Scale (NRS), raging from 0= no pain to 10= unbearable pain. The nocebo procedure was carried out after a pre-conditioning session in which two different conditioned stimuli were associated to either pain or no pain.

We found that the conditioned stimulus that was associated to pain was capable, when presented alone, of turning a tactile stimulus into pain.

These data suggest that a stressor, probably through anticipatory anxiety, can induce allodynic effects, whereby tactile stimuli become painful. These findings, along with previous data about placebo effects, indicate the powerful modulation of pain by placebos and nocebos.