RESPONSES OF ON AND OFF CELLS IN THE ROSTRAL VENTRAL MEDULLA TO STIMULATION OF VAGAL AFFERENTS AND CHANGES IN MEAN ARTERIAL BLOOD-PRESSURE IN INTACT AND CARDIOPULMONARY DEAFFERENTED RATS

The relationships between mean arterial blood pressure (MAP) and the a ctivity of putative pain modulatory neurons of the rostroventral medul la (ON and OFF cells) were determined in intact and cardiopulmonary de afferented rats. A total of 173 neurons were recorded from 97 rats as follows: 32 ON cells and 25 OFF cells from 39 intact rats; 32 ON cells and 20 OFF cells from 24 rats with bilateral sine-aortic deafferentat ion (SAD); 12 ON cells and 20 OFF cells from 19 rats with bilateral ce rvical vagotomy (CVAG); and 20 ON cells and 12 OFF cells from 15 rats with both SAD and CVAG. ON and OFF cells showed spontaneous fluctuatio ns in activity such that ON cell activity was negatively correlated wi th MAP whereas OFF cell activity was positively correlated with MAP un der conditions of no applied stimuli. These correlations were present in both intact and cardiopulmonary deafferented rats. Further, experim entally induced increases in MAP decreased ON cell activity and increa sed OFF cell activity in intact rats, but not in rats with SAD, CVAG, or the combination of SAD and CVAG. Experimentally induced decreases i n MAP decreased OFF cell activity in intact rats and rats with CVAG, b ut not in rats with SAD or the combination of SAD and CVAG. These find ings indicate that ON and OFF cells are modulated by baroreceptor acti vity, but baroreceptor input is not necessary for the spontaneous fluc tuations in ON and OFF cell activity. Electrical stimulation of vagal afferents (VAS) inhibited 60% of the OFF cells studied, excited 4%, an d produced biphasic effects consisting of excitation at low intensitie s and inhibition at greater intensities in 28% of all OFF eels. In gen eral, VAS excited the majority bf the ON cells studied, although there were significant differences between effects in intact and cardiopulm onary deafferented rats. Greater intensities of VAS that inhibited OFF cells and excited ON cells also inhibited the tail flick. Thus, inhib ition of OFF cells and excitation of ON cells was correlated with anti nociception. The effects of intravenous (i.v.) administration of 1.0 m g/kg morphine on neuronal activity did not differ between intact and c ardiopulmonary deafferented rats. Intravenous administration of morphi ne produced a sustained inhibition of 20.7% of all ON cells studied, p roduced a biphasic effect consisting of a brief excitation followed by a sustained inhibition in 62.1% of the ON cells, and had no effect on the activity of 17.2% of the ON cells. Morphine-produced inhibition o f ON cell activity was reversed by i.v. administration of naloxone HCl , but was not affected by i.v, administration of naloxone methobromide (NMB). However, pre-treatment with NMB attenuated the initial morphin e-produced excitation of ON cells. In studies of OFF cells, i.v. admin istration of morphine excited 40.0% of the OFF cells, produced a bipha sic effect consisting of an initial inhibition followed by excitation in 33.3% of the OFF cells, and had no effect on the activity of 26.7% of the OFF cells. Naloxone HCl reversed the effects of morphine within 1 min after administration, whereas NMB had no effect on the morphine -produced excitation of OFF cells. Intravenous administration of morph ine following pre-treatment with NMB excited the 2 OFF cells studied. These data suggest that ON and OFF cells in the rostroventral medulla not only receive converging input from cardiopulmonary and somatic aff erents, but may also function in the regulation of both systems. Speci fically, the excitation of ON cells and inhibition of OFF cells may de crease MAP and nociception, whereas the inhibition of ON cells and exc itation of OFF cells may increase MAP and nociception. This hypothesis contradicts previous hypotheses suggesting that inhibition of ON cell s and excitation of OFF cells attenuates nociception indicating that c urrent hypotheses on the function of ON and OFF cells require further analyses.