Stimulation-produced analgesia and its cross-tolerance between dorsal and ventral PAG loci

This study explored the development of tolerance to brain stimulation-produced analgesia in both dorsal and ventral periaqueductal gray (PAG) sites and the development of cross-tolerance between naloxone-reversible and non-reversible sites. Cross-tolerance was produced from non-naloxone-reversible sites to naloxone-reversible sites (NNR-NR) and from naloxone-reversible sites to non-naloxone-reversible sites (NR-NNR). The following conclusions can be drawn from the present study: (1) the descending pain inhibitory systems within the PAG do not operate in isolation of each other since cross-tolerance to chronic stimulation can be produced between systems; (2) the interaction between the two systems is apparently bi-directional in that cross-tolerance was produced from naloxone-reversible to non-reversible sites and vice versa; and (3) the interaction may be the result of a co-activation of opioid and non-opioid systems produced by electrical stimulation or by a co-utilization of a common neuronal substrate. It is speculated that serotonin is a neurotransmitter involved in the mechanism of convergence.