Evidence for two classes of nociceptive modulating neurons in the periaqueductal gray

The midbrain periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM) are important links to a neuronal network that modulates nociceptive transmission. In the RVM, 2 classes of cells have been identified that show changes in activity at the time of the tail-flick response (TF) elicited by noxious heat (Fields et al., 1983a). We now report that neurons in the PAG region also show changes in activity releated to TF. Extacellular recordings were made from the PAG and the ventrally adjacent tegmentum at sites from which it was possible to inhibit TF using stimulating currents of 10 μA or less. Cell activity, time of TF occurrence, and tail temperature were recorded during 5 repetitions of the heat stimulus. Periresponse and peristimulus histograms were plotted with reference to the TF and tail temperature, respectively. A significant number of neurons in the PAG region showed changes in activity that preceded the TF. 'Midbrain On-cells' (13.6% of the sample) displayed an abrupt increase in firing just prior to the TF. 'Midbrain Off-cells' (4.4%) paused just prior to the TF. The remaining neurons (241 of 294, or 82%) did not exhibit changes in firing prior to the TF. Thus, cells with changes in activity related to the TF are present in the PAG region as well as in the RVM. The PAG has a large projection to the RVM, and microinjection of morphine in the PAG increases activity of RVM Off-cells and decreases that of RVM On-cells. Thus, it is likely that On- and Off-cells found in the midbrain participate in the well-documented modulation of nociceptive reflexes by the PAG and that this action is mediated by TF-related neurons in the RVM.