Dependency of nociception facilitation or inhibition after periaqueductal gray matter stimulation on the context

Anxiety and/or fear can alter the nociceptive response in humans and animals. Slight stimulation of the dorsal periaqueductal gray matter (DPAG) produced anxiety/fear-related behaviour and hyponociception in escapable, non-anxiogenic nociceptive models. Our aim was to investigate the role of the DPAG in models of persistent, anxiogenic nociception. GLY (1, 10, 20, and 80 nmol/0.3 μl/60 s) was injected into the DPAG of rats, 5 min before formalin (2%/50 μl) injection either into the knee-joint or hind paw. In the knee-joint incapacitation test, GLY caused hypernociception at lower doses and hyponociception at higher doses. In the paw shacking test, GLY produced only hypernociception with the higher dose. Co-injecting GLY with 7-chlorokynurenic acid (7-CLK) or (+/−)-3-amino-1-hydroxy-2-pyrrolidone (HA-966) completely prevented the GLY effects in incapacitation and paw shacking tests, respectively. GLY injections outside the periaqueductal gray matter (PAG) did not change the nociception. Behavioural analysis indicated that formalin paw injection produced higher stress signals than knee-joint injection, as diminished exploratory behaviour, and stereotypy. The results suggest that activation of the DPAG through the GLYB/NMDA receptor is able to produce either facilitation or inhibition of nociception depending on the nociceptive context.