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Differential inhibitory effects of volleys from dorsal raphe nucleus upon spinal and spino-bulbo-spinal reflexes
Neuroscience Letters, 7 (1977) 291--2194 © Elsevier/North-Holland Scientific Publishers Ltd.
291
DIFFERENTIAL INHIBITORY EFFECTS OF VOLLEYS FROM DORSAL R,~PHE NUCLEUS UPCN SPINAL AND SPINO-BULBO-SPIT~AL REFLE.~f~S TOSHIKATSU YOKOTA Department of Physiology, Medical College of Shiga) Seta, Otsu) 520-21 (Japan) (Received November 30th, 1977) (Accepted December 5th, 1977)
SUMMARY
Electrical stimulation of the dorsal raphe nucleus cr just adjacent periaqueductal gray matter significantly inhibited the visceroint~ercost~J, reflex due to splanchnic A delta afferent volleys. The stimulation markedly suppressed the spino,bulbo-spinal reflex elicited by low threshold sural nerve voneys as well. The stimulation, however, had little effect o~'~the monosynaptic reflex in both flexor and extensor motoneurons. Recently, analgesia has been reported to result from elec~;rical s~imulation of the ventral portion of the periaqueductal gray matter (PAG) of the vicinity of the dorsal raphe nucleus (DRN). The stimulation appears capable of selectively reducing nociception [ 3,4]. In an attempt to learn more about d:ffferential action of volleys from tihe DRN, stimulation effects upon spinal and spinobulbo~pinal reflexes have been studied. Experiments were csrried out in 10 adult cats anesthetized wi'th urethanechloralose (urethane 438 mg/kg and chloralose 35 mg/kg). The animals were immobilized with gallamine triethiodlde and artificially ventilated. The posterior biceps-semitendinosus (PBST), gastrocnemius-soleus (GS), surai (Sur) and splanchnic (Spl) nerves were prepared from stimulation, and the L7 and $1 ventral roots together with the lowest three intercostal nerves for recording. A train of 5 pulses at 400/sec was applied through a concentric bipolar electrode to the DRN or ventral PAG. Each pulse was 0.5 msec in duration and less than 0.6 mA in intensity. After each expenment~ serivl frozen sections of 40 ~m were stained with cresyl violet to locate the elect.rode tip in the midbrain. Afferent fibers in the Spl nerve fall into three categories: A/~, A8 and C [2]. There is no reflex discharge in the lower intercostal nerves with Spl stimulation sufficiently strong to act,s'rate maximally the A~ fibers. The viscerointercostal reflex appears and increases in size upon stimulation at intensities sufficient to excite smaller A8 fibers but too weak to activate B fibers. No significant part of the reflex volleys is macle up of a dorsal root reflex [ 1 ]. In all the cats tested midbrain stimulation inhibited the viscerointercost.al reflex.
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Fig. 1. Time course of inhibition of viscerointercostal reflex. Reflex discharges were elicited in the 12th intercostal nerve by splanchnic nerve stimulation, the intensity of which was two times threshold for reflex discharge. This was preceded by a conditioning stimulus (0.15 m A ) at the intezvais indicated on the gr::ph (abscissa). The ordinate is the size of the viscerointercostal reflex. The 100% of the graph is the mean size of the control reflex. Sample records are illustrated above, indicating the time in msec ~etween the conditioning and test volleys. The photomicrograph indicates the s i ~ .:f c~nditiv==.ng stimulation.
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293
As illustrated in Fig. 1, the maximum inhibitory effect was obtained at a conditioning-test interval between 40 and 100 msec. When the intensity of Spl stimulation was about two times threshold for reflex discharge, the maximum inhibition ranged from 65% to 91%. When applied to the DRN cr just, ~djacent PAG, midbrain stimulation had little effect on monosynaptic PBST and GS reflexes, although it exerted a powerful inhibitory action upon the viscerointercostal reflex. When applied more laterally, midbrain stimulation capable of inhibiting the viscerointercostal reflex resulted in facilitation of the monosynaptic PBST reflex, together with inhibition of the monosynaptic GS reflex. Stimulation of the Sllr nerve elicits two different kinds of reflex discharges from L7 or S~ ventral root: propriospinal and spino-bulbo-spinal [6]. The spino-bulbo-spinal (SBS) reflex is elicited by low threshold cutaneous aff~rents
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Fig. 2. Time course of inhibition of sural reflex. Reflex disch~ges evoked by Sur (1.5 V~ 0.3 msec) were recorded in the L 7 ventral root and conditioned by a tetanus (0.4 mA) to the DRN. Both the size of the short latency propriospinal reflex (filled triangIes) and ~ha~ ~f the long latency SBS r,~flex (filled circles) were plotted against the time between the conditioning and test volleys. Sample traces, from which the plots are taken, vi'e vhown a~ove. The site of conditioning stimulation is indicated in tile photomicrograph.
2~4
[ 5]. As illustrated in Fig. 2, the midbrain stimulation markedly suppressed the long latency SBS reflex, while it only slightly inhibited the short latency propriospinal reflex. After an intravenous administration of 0.1 mg/kg strychnine, the viscerointercostal and SBS reflexes were enhanced, but the midbrain stimulation markedly inhibited these reflexes. Midbrain stimulation, on the other hand, did not elicit any appreciable dorsal root potentials. It had no significant effect upon dorsal root potentials due to cutaneous and muscle "afferent volleys either. REFERENCES 1 2 3 4 5 6
Downman, CB,B., Skeletal muscle refle~:es of splanchnic and intercostal nerve origin in acute spinal and decerebrate cats, J~ Neurophysiol., 18 (1955) 2 1 7 - 2 3 5 . Gernandt, B. and Zotterman, Y., Intesthlal pain: an electrophysiological investigation on mesenteric nerves, Acta physiol, scand., 12 (1946) 56--72. Mayer, D.J., Wolfle, T.L., Akil, H., Carder, B. and Liebeskind~ J.C., Analgesia from electrical stimulation in the brains~em of the rat, Science, 174 (1971 ) 1351--1354. Oliveras, J.L., Besson, J.M., Guilbaud, G and Liebeskind, J.C., Behavioral and electrophysiological evidence of pain inhibition from midbrain stimulation in the cat, Exp. Brain Res., 20 (1974) 32--44. Shiwamur.a, M. and Akert, K., Peripher~ nervous relations of propriospinal and spinobulbo-spinal re~ex systems, Jap. J. Physiol., 15 (1965) 638--647. Shimamura, M. and Livingston, R.B.~ Longitudinal conduction systems serving spinal and brai~lstem coordhlation, J. Neurophysiol., 26 (1963) 258--272.
291
DIFFERENTIAL INHIBITORY EFFECTS OF VOLLEYS FROM DORSAL R,~PHE NUCLEUS UPCN SPINAL AND SPINO-BULBO-SPIT~AL REFLE.~f~S TOSHIKATSU YOKOTA Department of Physiology, Medical College of Shiga) Seta, Otsu) 520-21 (Japan) (Received November 30th, 1977) (Accepted December 5th, 1977)
SUMMARY
Electrical stimulation of the dorsal raphe nucleus cr just adjacent periaqueductal gray matter significantly inhibited the visceroint~ercost~J, reflex due to splanchnic A delta afferent volleys. The stimulation markedly suppressed the spino,bulbo-spinal reflex elicited by low threshold sural nerve voneys as well. The stimulation, however, had little effect o~'~the monosynaptic reflex in both flexor and extensor motoneurons. Recently, analgesia has been reported to result from elec~;rical s~imulation of the ventral portion of the periaqueductal gray matter (PAG) of the vicinity of the dorsal raphe nucleus (DRN). The stimulation appears capable of selectively reducing nociception [ 3,4]. In an attempt to learn more about d:ffferential action of volleys from tihe DRN, stimulation effects upon spinal and spinobulbo~pinal reflexes have been studied. Experiments were csrried out in 10 adult cats anesthetized wi'th urethanechloralose (urethane 438 mg/kg and chloralose 35 mg/kg). The animals were immobilized with gallamine triethiodlde and artificially ventilated. The posterior biceps-semitendinosus (PBST), gastrocnemius-soleus (GS), surai (Sur) and splanchnic (Spl) nerves were prepared from stimulation, and the L7 and $1 ventral roots together with the lowest three intercostal nerves for recording. A train of 5 pulses at 400/sec was applied through a concentric bipolar electrode to the DRN or ventral PAG. Each pulse was 0.5 msec in duration and less than 0.6 mA in intensity. After each expenment~ serivl frozen sections of 40 ~m were stained with cresyl violet to locate the elect.rode tip in the midbrain. Afferent fibers in the Spl nerve fall into three categories: A/~, A8 and C [2]. There is no reflex discharge in the lower intercostal nerves with Spl stimulation sufficiently strong to act,s'rate maximally the A~ fibers. The viscerointercostal reflex appears and increases in size upon stimulation at intensities sufficient to excite smaller A8 fibers but too weak to activate B fibers. No significant part of the reflex volleys is macle up of a dorsal root reflex [ 1 ]. In all the cats tested midbrain stimulation inhibited the viscerointercost.al reflex.
t
~.$~
0
I
•
•
I
•
• •
I
I
•
•
•
:
I
5'0
•
•
I"
~
: •
•
:
!
I
i lOO
I•
6
200
•
•
/.~)0
, zoo
I
] 0.~ mV
.
Conditioning-Test Interval (msec)
•
•
•
.
100
•
Q
I
o
Fig. 1. Time course of inhibition of viscerointercostal reflex. Reflex discharges were elicited in the 12th intercostal nerve by splanchnic nerve stimulation, the intensity of which was two times threshold for reflex discharge. This was preceded by a conditioning stimulus (0.15 m A ) at the intezvais indicated on the gr::ph (abscissa). The ordinate is the size of the viscerointercostal reflex. The 100% of the graph is the mean size of the control reflex. Sample records are illustrated above, indicating the time in msec ~etween the conditioning and test volleys. The photomicrograph indicates the s i ~ .:f c~nditiv==.ng stimulation.
ZO-
40-
60-
120 • %/ 100t~ C°ntr°l
O
~,,,,,
293
As illustrated in Fig. 1, the maximum inhibitory effect was obtained at a conditioning-test interval between 40 and 100 msec. When the intensity of Spl stimulation was about two times threshold for reflex discharge, the maximum inhibition ranged from 65% to 91%. When applied to the DRN cr just, ~djacent PAG, midbrain stimulation had little effect on monosynaptic PBST and GS reflexes, although it exerted a powerful inhibitory action upon the viscerointercostal reflex. When applied more laterally, midbrain stimulation capable of inhibiting the viscerointercostal reflex resulted in facilitation of the monosynaptic PBST reflex, together with inhibition of the monosynaptic GS reflex. Stimulation of the Sllr nerve elicits two different kinds of reflex discharges from L7 or S~ ventral root: propriospinal and spino-bulbo-spinal [6]. The spino-bulbo-spinal (SBS) reflex is elicited by low threshold cutaneous aff~rents
~ t
1 ~ ~ .
70
150
tttttt
t
~
JO.1 mV
lOrnsec
% 120- Con
®
100"
="li
80-
i,
... .! ....
60-
/
40-
,2
20.
,...,-
0 tttfi
so
loo
®
200
Condi t ion i n g - T e s t
360
400
500
! nt e r v a l ( rnsec )
Fig. 2. Time course of inhibition of sural reflex. Reflex disch~ges evoked by Sur (1.5 V~ 0.3 msec) were recorded in the L 7 ventral root and conditioned by a tetanus (0.4 mA) to the DRN. Both the size of the short latency propriospinal reflex (filled triangIes) and ~ha~ ~f the long latency SBS r,~flex (filled circles) were plotted against the time between the conditioning and test volleys. Sample traces, from which the plots are taken, vi'e vhown a~ove. The site of conditioning stimulation is indicated in tile photomicrograph.
2~4
[ 5]. As illustrated in Fig. 2, the midbrain stimulation markedly suppressed the long latency SBS reflex, while it only slightly inhibited the short latency propriospinal reflex. After an intravenous administration of 0.1 mg/kg strychnine, the viscerointercostal and SBS reflexes were enhanced, but the midbrain stimulation markedly inhibited these reflexes. Midbrain stimulation, on the other hand, did not elicit any appreciable dorsal root potentials. It had no significant effect upon dorsal root potentials due to cutaneous and muscle "afferent volleys either. REFERENCES 1 2 3 4 5 6
Downman, CB,B., Skeletal muscle refle~:es of splanchnic and intercostal nerve origin in acute spinal and decerebrate cats, J~ Neurophysiol., 18 (1955) 2 1 7 - 2 3 5 . Gernandt, B. and Zotterman, Y., Intesthlal pain: an electrophysiological investigation on mesenteric nerves, Acta physiol, scand., 12 (1946) 56--72. Mayer, D.J., Wolfle, T.L., Akil, H., Carder, B. and Liebeskind~ J.C., Analgesia from electrical stimulation in the brains~em of the rat, Science, 174 (1971 ) 1351--1354. Oliveras, J.L., Besson, J.M., Guilbaud, G and Liebeskind, J.C., Behavioral and electrophysiological evidence of pain inhibition from midbrain stimulation in the cat, Exp. Brain Res., 20 (1974) 32--44. Shiwamur.a, M. and Akert, K., Peripher~ nervous relations of propriospinal and spinobulbo-spinal re~ex systems, Jap. J. Physiol., 15 (1965) 638--647. Shimamura, M. and Livingston, R.B.~ Longitudinal conduction systems serving spinal and brai~lstem coordhlation, J. Neurophysiol., 26 (1963) 258--272.