1. The descending inhibition of neuronal responses by focal electrical stimulation or glutamate microinjections in the periaqueductal gray (PAG) or rostral ventromedial medulla (RVM) was quantitatively studied on 61 spinal neurons in halothane-N2O-anesthetized paralyzed rats. Thirty-six neurons were located in the medial L6-S1 spinal cord and were consistently and reproducibly excited by distension of the descending colon and rectum (75 mmHg). Twenty-five other neurons were located in the dorsal horn of spinal segemnts L3-L5 and were consistently and reproducibly excited by radiant heating (50°C) of the glabrous skin of the plantar surface of the left (ipsilateral) hind foot. 2. The inhibition of neuronal responses to colorectal distension by stimulation in the PAG or RVM differed quantitatively when examined on the same spinal neurons. Inhibition of neuronal responses to distension occurred at a lower mean threshold of stimulation in the RVM than in the PAG. The mean intensity of stimulation in the RVM producing an attenuation to 50% of the control response to colorectal distension (75 mmHg, 20 s) was significantly lower than the mean intensity of stimulation in the PAG producing a 50% attenuation of the same spinal units. The mean magnitude of inhibition produced by stimulation in the RVM was significantly greater than that produced on the same spinal units by the same intensity of stimulation in the PAG. However, stimulation in the RVM and PAG produced the same mean percent change in inhibition per 25-μA increase in the intensity of stimulation. Thus the slopes of the lines of recruitment of descending inhibition from the PAG and RVM as a function of increasing intensities of stimulation are the same; the lines of recruitment of inhibition are parallel. These findings are virtually identical to those found by others in studies of modulation of neuronal responses to noxious heating of the skin. 3. Neuronal intensity coding to both graded heating of the hindfoot and graded colorectal distension was monotonic and accelerating and could be expressed as linear stimulus-response functions (SRFs) in the temperature and pressure ranges studied (46-52°C, 25-100 mmHg). Stimulation in the PAG modulated the SRFs differently than did stimulation in the RVM. Stimulation in the PAG decreased the slope of the SRFs without affecting the units' thresholds of response, thus influencing the gain control of both cutaneous and visceral nociception in the spinal cord. Stimulation in the RVM produced an essentially parallel shift of the SRF to the right, influencing the set point of response to cutaneous and visceral nociceptive stimulation. 4. Glutamate is an excitatory amino acid believed to excite only cell bodies. The microinjection of 50 nmol (in water, 0,5 μl) sodium glutamate into the PAG or RVM produced an immediate, but short-lived, inhibition of the neuronal response to colorectal distension, indicating that inhibition by electrical stimulation in the PAG or RVM is likely a result of excitation of cell bodies. 5. The inhibition of neuronal responses to colorectal distension or heating of the skin was indistinguishable, occurring at the same brain sites at comparable intensities of stimulation and producing similar modulations of SRFs characterizing neuronal responses to graded noxious stimuli. These data support the hypothesis that systems of descending inhibition originating in the PAG and RVM regulate the processing of both cutaneous and visceral nociception at the spinal level in a similar, if not identical manner.
