Single neurons in the rat medulla responsive to nociceptive stimulation

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Single neurons in the rat medulla responsive to nociceptive stimulation In a recent paper Burton ~ described the somatic sensory properties of single neurons in the caudal bulbar reticular formation of the cat. Of particular interest was the observation that the majority of units (over 70 700)responded only to nociceptive stimulation. This paper describes similar observations in another species, the rat. Portions of the study were reported earlierL Rats were maintained areflexic with sodium pentobarbital. Deeper anesthesia tended to slow the spontaneous activity and reduce the overall responsiveness of the units. Discharges were recorded extracellularly by conventional techniques. Isolation of single cells was easily achieved presumably because the cells are relatively large and widely separated. Over 100 units were studied extensively; 59 of these were localized in histological sections. This report will describe the response characteristics, receptive fields and anatomic location of cells which responded only to nociceptive stimulation of the skin. Pricking, cutting, pinching, and temperatures above about 50°C were all effective while non-noxious stimuli (touch, heavy pressure, rubbing, clicks and light flashes) were all ineffective. In the examples that follow the standard stimulus consisted of squeezing the skin with small serrated forceps with sufficient force to make an indentation, a decidedly painful stimulus when applied to the human. This seemingly crude

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Fig. 1. Interspike interval dot patterns illustrating the range o f excitatory a n d inhibitory responses.

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Fig. 4. Examples of receptive fields. stimulus was very efficient for a rapid determination of nociceptive receptive areas. More sophisticated stimuli for equivalent units in the cat have been described elsewhere 2. Response characteristics. Approximately 50 ~o of the units were 'spontaneously' active in the absence of intentional stimulation. At least some of this activity was due to continuous input from surgical wounds and previous nociceptive stimulation since local anesthesia applied to the appropriate receptive field could reduce or eliminate this ongoing activity. Rates varied from a few to over 100 impulses/sec between units. Nociceptive stimulation could either facilitate or inhibit the spontaneous rate depending upon the unit type and/or the peripheral locus of the stimulus. Both the magnitude and the temporal characteristics of the rate change varied depending upon both the particular unit and the locus of stimulation, but were quite reproducible for an individual unit. Fig. 1 shows the maximum response of 8 units chosen to illustrate the wide range of responsiveness encountered. The data are presented as interspike interval dot patterns. Each dot represents a single spike and its distance from the abscissa (0 msec) measures the length of time in msec since the last spike. The abscissa measures real time. A dot below the abscissa indicates that no spike occurred during the last 250 msec, the maximum time interval on the ordinate. The bar below the abscissa Brain Research, 24 (1970) 525-529

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Fig. 5. Localization of the nociceptive units. Cu. = cuneate nucleus; Gr. = gracile nucleus; I.O.C. inferior olivary complex; L. Cu. = lateral cuneate nucleus; L.R. = lateral reticular nucleus; Sp. V = spinal trigeminal nucleus; XII = hypoglossal nucleus. marks the application of the stimulus. Unit 4, for example, had no spontaneous rate, responded vigorously (intervals < 50 msec) at the beginning of the stimulus (0 sec), maintained this rate fairly well for the duration of the stimulus and decreased firing immediately and almost completely at the offset of the stimulus (60 sec). At the other extreme unit 1 discharged only a few times at the onset of the stimulus. The excitatory units illustrated here happen to have no spontaneous rate, but this was not true of all units of this type. Inhibitory effects ranged from brief interruption of a regular spontaneous rate (unit 5) to nearly complete cessation of firing for the duration of stimulation (unit 8). Receptive fields. Approximately 90 ~ of the units had both excitatory as well as inhibitory receptive fields; 90 ~ had bilateral input; 80 ~o of the fields included some part of the head. Fig. 2 illustrates these points. Stimulation of the ipsilateral (right) lower jaw produced m a x i m u m excitation. Other parts of the face were less excitatory. The peripheral field for m a x i m u m inhibition was the tip of the tail. All 4 paws and the contralateral lower jaw were also inhibitory. Other examples are presented in Fig. 3. In the top row are 3 units with small facilitatory receptive fields on the nose, ear and tail. In the next row are 3 inhibitory fields. Row 3 illustrates remarkably symmetrical fields, inhibitory on one side, excitatory on the other. In the last row are 3 examples of equally remarkable symmetrical fields, inhibitory and excitatory on both sides. Many units had more complex inputs as illustrated in Fig. 4. Anatomical location. The units were localized on 3 standard sections in Fig. 5. The one on the right is at the level of the obex, the middle section approximately 1/3 m m further caudal and the one on the left 1/3 m m caudal to the second. The bars m a r k the location of units firing in synchrony with some part of the respiratory cycle. Most of the nociceptive units were found in the ventral reticular nucleus 3, those with receptive fields restricted to the head (small dots) were located more medial to those with fields including other parts of the body (large dots). 'Pure' nociceptive units were restricted to the relatively small region indicated on the 3 sections and constituted more than two-thirds of the population. Slightly rostral to the obex, nociceptive cells

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were replaced by cells responsive to non-noxious touch-pressure and some with mixed (both noxious and non-noxious) fields. These results differ from those in the cat 1 primarily in the rich variety of receptive fields found in the rat. Whether or not these neurons mediate sensory processes or reflex activity or both, taken collectively they could provide very accurate specification of the peripheral location of a noxious stimulus. Laboratory of Neurophysiology, and Department of Physiology, University of Wisconsin Medical Center, Madison, Wisc. 53706 (U.S.A.)

ROBERT M. B E N J A M I N

1 BENJAMIN,R. M., Single neurons in the rat medulla responsive to nociceptive stimulation, Proc. XXIl int. Physiol. Congr., Leyden, 11 (1962) 1039. 2 BURTON, H., Somatic sensory properties of caudal bulbar reticular neurons in the cat (Felis domestica), Brain Research, 11 (1968) 357-372. 3 MOSSEN,H., AND OLSZEWSKI,J., A Cytoarchitectonic Atlas of the Rhombencephalon of the Rabbit, Karger, New York, 1949. (Accepted October 14th, 1970)

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