Involvement of cellular prion protein in the nociceptive response in mice

The role of the cellular prion protein (PrPc) in neuronal functioning includes neuronal excitability, cellular adhesion, neurite outgrowth and maintenance. Here we investigated the putative involvement of the PrPc function on the nociceptive response using PrPc null (Prnp0/0) and wild-type (Prnp+/+) mice submitted to thermal and chemical models of nociception. PrPc null mice were more resistant than wild-type mice to thermal nociception of the tail-flick test. However, no significant difference was found on the hot plate test. In the acetic acid-induced visceral nociception, PrPc null mice showed an enhanced response when compared to wild-type mice. However, there was no difference between Prnp0/0 and wild-type mice on glutamate- and formalin-induced licking behaviour and Freund's Complete Adjuvant (FCA)-induced mechanical allodynia. PrPc null mice developed significantly lower paw edema than wild-type mice. In addition, the visceral conditioning stimuli produced by a previous injection of acetic acid (20 days before testing) significantly reduced early and late phases of formalin-induced nociception in wild-type mice. In contrast, the same pre-treatment did not alter the formalin response in PrPc null mice. These results indicate a role of PrPc in the nociceptive transmission, including the thermal tail-flick test and visceral inflammatory nociception (acetic acid-induced abdominal constriction). Our findings show that PrPc is involved with a response mediated by inflammation (paw edema) and by visceral conditioning stimuli.