Neuroscience Letters, 39 (1983) 125-130
125
Elsevier Scientific Publishers Ireland Ltd.
SOMATOTOPIC DISTRIBUTION OF TRIGEMINAL NOCICEPTIVE SPECIFIC NEURONS WITHIN THE CAUDAL SOMATOSENSORY THALAMUS OF CAT
TOSHIKATSU YOKOTA and NORIO MATSUMOTO
Department oj" Physiology, Medical College of Shiga, Seta, Otsu 520-21 (Japan) (Received April 22nd, 1983; Revised version received and accepted May 30th, 1983)
Key words: nv,:leus ventralis posterior medialis - trigeminal system - nociception - thalamus somatotopy - ~omatosensation - cat
Trigeminal nociceptive specific (NS) neurons were found within the shell region of the caudal part of nucleus ventralis posterior medialis (VPM) of cat. They showed a somatotopic organization. Namely, the mandibular division was represented along the border between the VPM proper and nucleus ventralis posterior medialis parvocellularis (VPMpc). The ophthalmic division was represented dorsolaterally. The maxillary division fell in between. No other types of trigeminal nociceptive neurons were found in the caudal VPM where trigeminal NS neurons were encountered. After cooling the dorsolateral surface of the medulla oblongata caudal to the obex, responses of NS neurons within the shell region of the caudal VPM to noxious stimulation of the peripheral receptive field reversibly disappeared. The responses were also eliminated by the contralateral trigeminal tractotomy at the level of the obex. It was inferred that trigeminal NS neurons within the shell rcgion of the caudal VPM receive nociceptive input relayed via NS neurons located within the marginal layer of the trigeminal subnucleus caudalis.
Previous studies revealed 3 different categories of trigemix~al nociceptive neurons within the medulla oblongata differentially located caudal to the obex [17,18]. Nociceptive specific (NS) neurons, with high mechanical thresholds, are located in the marginal layer and outer zone of substantia gelatinosa of the trigeminal subnucleus caudalis. Wide dynamic range (WDR) neurons, which have low mechanical threshold but respond maximally to noxious mechanical stimulation, are found in the lateral part of subnucleus reticularis dorsalis. The dorsolateral part of subnucleus reticularis ventralis (SRV) contains trigeminal nociceptive neurons of a special category; they regularly respond to mechanical stimulation of the ipsi- or bilateral cornea. Many of them are also excited by noxious mechanical stimulation of the ipsi- or bilateral pinna, tongue and/or face. Some of them are also responsive to tapping the dorsum of ipsilateral nose and/or electrical stimulation of ipsi- or bilateral tooth pulp afferents. Trigeminothalamic neurons are included in each category except for NS neurons in substantita gelatinosa. The question has been raised whether the segregation of the 3 different categories of trigeminal 0304-3940/83/$ 03.00 ~-~ 1983 Elsevier Scientific Publishers Ireland Ltd.
126
nociceptive neurons is maintained at the level of the thalamus. In the present paper we report that the shell region of the caudal part of nucleus ventralis posterior medialis (VPM) contains trigeminal NS neurons in somatotopic order, but the two other types of trigeminal nociceptive neurons are not found in the region where NS neurons are located. Experiments were carried out in 28 adult cats anesthetized with intravenous (i.v.) injection of 3.5 ml/kg of urethane-chloralose solution (urethane 125 mg/ml and chloralose 10 mg/ml), supplemented as required. During single unit recordings, the animals were immobilized with pancuronium bromide (0.4 mg/kg, i.v.) and artificially ventilated. Single unit recordings were made using glass capillary microelectrodes filled with 2o7o Pontamine sky blue in 1 M sodium acetate. Recording sites of single unit activities were marked by passing a negative current of 5 #A through the microelectrode for 5 min, depositing a small amount of blue dye. They are reconstructed on 50 #m frozen sections. Nucleus ventralis posterior medialis (VPM) [9] consists of two parts, i.e. the VPM proper and its parvocellular part (VPMpc) [12,15]. In the present experiments, trigeminal somatosensory neurons were found in the "v?~M proper but not in VPMpc. The majority of trigeminal somatosensory neurons maximally responded to innocuous mechanical stimulation such as hair movement or light touch. Apparently they were low-threshold mechanoreceptive (LTM) neurons. In the caudal somatosensory thalamus, however, trigeminal NS neurons were found at the dorsal a n d / o r ventral end of a row of LTM neurons in penetrations passing through the VPM proper. Histological examinations revealed that they were located at or near the margin of the VPM proper, i.e. within the shell region of the VPM proper. They were distributed in the caudal third of the VPM proper, the rostral end of which was approximately AP + 7.5 mm in the stereotaxic coordinates. They were not found along the border between tb.e VPM proper and nucleus ventralis posterior iateralis (VPL). Neither WDR neurons nor neurons having similar receptive field characteristics to those of SRV neurons were found in the caudal VPM where trigeminal NS neurons were encountered. It is well known that trigeminal LTM neurons in the VPM proper show a somatotopic organization [7]. Trigeminai NS neurons in the caudal VPM had a circumscribed contralateral receptive field adjacent to or overlapping with that of an LTM neuron lying in close proximffy in the same microelectrode penetration. Consequently, they also showed a somatotopic organization. As shown in Fig. I, NS neurons having a receptive field in the mandibular division were located along the border between the VPM proper arid VPMpc. NS neurons having a receptive field in the ophthahnic division were found dorsolaterally. NS neurons having a receptive field in the maxillary division fell in between. In order to understand the origin of trigeminal nociceptive input onto the shell region of the caudal VPM, effects of cooling the contralateral trigeminal spinal tract and subnucleus caudalis were studied. A hollow metal thermode 5 × 6 mm was
127
•
,,\
_
,"
,;,,.
.,
~"
*
•
•
.
.O
".'
~
.,.,.
" : .."::'L~',--¢.
.....'.
•
~
...',.,
.'*
•
".:*,:
...
"
¢
•
"~'-.-
•
"~..
",~
..",,.
ad
:~ , ,
.,
•
~. e ' .
• . .
,..'~ " . • . -
"
"~
....
~ia".~"-4
.';~
",,~'-.'.
"~*."
..
" ..... ~'~:."
"~..'7...'.
~
., .
,
".J.~,l.
" ' ,
:.,:,,.~'...,-:..'" .",.:,. ~..:..,~: :. ':, :...
: - .--" " ... •
.
-
~:,
..'.
[.
"
" •
.
"
"...~
.
.
.
.
.
• ~,
,,
•
;1
,.-.
,.
:~'~...?-":'.':.I.~.~:.'.--:'.;~ .
"
" " ....
" " - " •
"
"
-
"
"
". ,,
-
•
.
..
•
.
""
.
.
-"
" "
..
: .
.,,'.,"
.- : . .-..., .,.," '
•
,,
.
.
,
i |
-
"
.
. .
"
-.
.
.
. I m m
•
•
.
.
B
i........:
~_..~
~. _.
Fig. 1. Somatotopic distribution of trigeminal NS neurons within the shell region of caudal VPM. A: locations of neurons obtained in 5 penetrations through the VPM proper made during one experiment. O, locations of trigeminal NS neurons; O, locations of trigeminal LTM neurons; o, locations of spinal LTM neurons. B: receptive fields of the ~rigeminal NS neurons whose locations are shown in A.
128
positioned on the dorsal surface of the contralateral medulla oblongata caudal to the obex, and was circulated with ice water, after having tested the receptive field properties and responses to electrical stimulation of the cutaneous receptive field of an NS neuron. The thermode overlaid the contralateral trigeminal subnucleus caudalis and extended from the obex to the rostralmost first cervical dormd rootlet. In 5 NS units tested, 10 min cooling abolished their responses to noxious mechanical as well as electrical stimulation of the cutaneous receptive field. The responses recovered 10 min after the cessation of cooling. The results suggest that nociceptive responses of thalamic NS neurons depend on the integrity of the caudal medulla
A
B
Location ~..;~-",
I
:t..~;~.....
~
..,.
/5-~.-~_--'-;~"-..~-~. . . -
+
-
' .
Receptive Field
: ii i iii --' i
+++
-., , . ~.,.r..,~+..
.
C
+.+
..+
,.?;i:..: ~, .
.
/'
..
Before Cooling '
+ +i
/./~~~'//' D
j
During Cooling
t
10 rain After Cessation of Cooling
ii
I
~.W'
'
E
j
I I
t
ii
I
'~IIj
,
i i!
,~Ytg,'¢'
4
'
L
1 0.1my
! ,J,,41
l
lOmsec
Fig. 2. Effects o t " cooling the dorsolateral surface of the contralateral caudal medulla oblongata on responses of a NS neuron in the caudal VPM proper. A: location of the neuron in the thalamus i n d i c a t e d by an arrow. B: receptive field of tile neuron. C: responses of the neuron to electrical stimulation of the receptive field before cooling was started. D: responses of the neuron to the same stimulation 10 m i n after the beginning of tooting. No spike discharges were elicited. E: responses of the neuron 10 min after tile cessation of cooling.
129
oblongata. The results were further confirmed by experiments using contralateral trigeminal tractotomy in two cats. After interrupting the spinal tract of the trigeminal nerve at the level of the obex, responses of thalamic NS neurons to noxious mechanical as well as electrical stimulation of the receptive field disappeared, but responses of LTM neurons encountered in the same microelectrode penetrations remained unchanged. Within the caudal medulla oblongata, trigeminothalamic NS neurons are located exclusively in the marginal layer of the trigeminal subnucleus caudalis [17,18]. Therefore, these result that nociceptive input onto NS neurons within the shell region of the caudal VPM is relayed via NS neurons in the marginal layer of the trigeminal subnucleus caudalis. Furthermore, they indicate that the somatotopic organization of trigeminal nociceptive representation found within the marginal layer of the trigeminal subnucleus caudalis [16,17] is maintained at the level of the thalamus. It was previously uncertain whether the V P L - V P M complex of the thalamus receives nociceptive input [13]. Recently, however, NS neurons were found in the shell r~ .',ion of VPL in the cat [8,1 l] and monkey [10]. The present findings in the caudal CPM are complementary to these reports. It is now difficult to question the existence of nociceptive neurons in the ventrobasal complex of the thalamus. In the present experiments, no type of trigeminal nociceptive neurons other than NS neurons were found in the caudal VPM where trigeminal NS neurons g zre encountered, i.e. trigeminal NS neurons were segregated. In contrast, Kenshalo et al. [10] found both NS and WDR neurons in the caudal part of VPL (VPLc) in the monkey, and these two types of nociceptive neurons were intermixed. According to Carstens and Trevino [3], VPL receives nociceptive input primarily from lamina I (marginal layer) of the spinal cord dorsal horn. Other investigators have reported that lamina I of the spinal cord dorsal horn contains not only NS Lut a~ o WDR neurons [1,2,4,14,16]. In contrast, the marginal layer of the trigeminal subnucleus caudalis contains only NS neurons [17,18]. It therefore seems likely that the difference between the caudal VPM and VPL in segregation of NS neuror reflects the difference between the marginal layer of the trigeminal subnucleus caudalis and lamina I of the spinal cord dorsal horn. Craig and Burton [5] reported that nucleus submedius of the medial thalamus receives nociceptive input from the marginal layer of the trigeminal subnucleus caudalis and lamina I of the spinal cord dorsal horn. However, this nucleus projects to the prefrontal agranular cortex in the cat [6]. It was suggested that neurons in this nucleus may be involved in affective rather than sensory-discriminative aspects of pain [5]. The present experiments indicated that the VPM proper, a classical somatosensory relay nucleus, receives topographically organized nociceptive projection from the marginal layer of the trigeminal subnucleus caudalis. It may be conceivable that NS neurons in the shell region of the caudal VPM subserve sensorydiscriminative aspects of pain.
130 1 Appelbaum, A.E., Leonard, R.B., Kenshalo, D.R., Jr., Martin, R.F. and Willis, W.D., Nuclei in which functionally identified spinothalamic tract neurons terminate, J. comp. Neurol., 188 (1979) 575-586. 2 Bennett, G.J., Abdelmoumene, M., Hayashi, H. and Dubner, R., Physiology and morphology of substantia gelatinosa neurons intracellularly stained with horseradish peroxidase, J. comp. Neurol., 194 ( ! 980) 809- 827. 3 Carstens, E. and Trevino, D.L., Laminar organization of spinothalamic neurons in the cat determined by the retrograde transport of horseradish peroxidase, J. comp. Neurol., 182 (1978) 151-166. 4 Chung, J.M., Kenshalo, D.R., Jr., Gerhart, K.D. and Willis, W.D., Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys. J. Neurophysiol., 42 (1979) 1354-1369. 5 Craig, A.D., Jr. and Burton, H., Spinal and medullary lamina ! projection to nucleus submedius in medial thalamus: a possible pain center, J. Neurophysiol., ~5 (1982) 443-466. 6 Craig, A.D., Jr., Wiegand, S.J. and Price, J.L., The thalamo-cortical projection of the nucleus submedius in the cat, J. comp. Neurol., 206 (1982) 28-48. 7 Darian-Smith, I., The trigeminal system. In A. lggo (Ed.), Handbook of Sensory Physiology, Vol. 2, Somatosensory System, Springer Verlag, Berlin, 197.s, i,7 271-314. 8 Honda, C.N., Mense, S. and Peri, E.R., Neurons in ventroba~al region of cat thalamus selectively responsive to noxious mechanical stimulation, J. Neurophysiol., 49 (1983) 662-673. 9 Jasper, H.H. and Ajmone Marsan, C.. A Sterecsiaxl~: ~tlas of ~he Diencephalon of the Cat, Nat. Res. Council, Ottawa, Canada, 1954. !0 Kenshalo, D.R., Jr., Giesler, G.J., l.eonanl, R.B. and Willis, W.D., Responses of neurons in primate ventral posterior lateral nucleus to noxious stimuli, J. Neurophysiol., 43 (1980) 1594-1614. l l Kniffki, K.D. and Mizumura, K.. Responses of neurons in VPL and VPL-VL region of the cat to algesic stimulation of muscle and tendon, J. Netirophysiol., 49 (1983) 649-661. ! 2 Niimi, K. and Kuwabara, E., The dorsal thalamus of the cat and comparison with monkey and man, J. Hirnforsch., 14 ~1973) 303-325. 13 Poggio. G.F. and Mountcastle, V.B.. A study of the functional contributions of the lemniscal and spinothalamic systems to somatic sensibility, Bull. Johns Hopk. Hosp., 106 (1960) 266-316. 14 Price, D.D., Hayashi, H., Dubner, R. and Ruda, M., Functional relationships between neurons of nmrginal and substantia gelatinosa layers of primate dorsal horn, J. Neurophysiol., 42 (1979) 1590- ! 608. 15 Rinvik, E., A re-evaluation of the cytoarchitecture of the ventral nuclear complex of the cat's thalamus on the basis of corticothalamic connections, Brain Res., 8 (1968) 237--254. 16 Tsubaki, T. and Yokota, T., Heat-evoked responses of dorsal horn nociceptive neurons in the monkey, Jap. J. Physiol., 33 (1983) 245-263. 17 Yokota, T. and Nishikac.a, N., Somatotopic organization of trigeminal neurons within caudal medulla oblongata, in D. Anderson and B. Matthews (Eds.), Pain in the Trigeminal Region, Elsevier/North-Holland, Amsterdam, 1977, pp. 243-257. 18 Yokota, T., Nishikawa, N. and Nishikawa, Y., Trigeminal nociceptive neurons in the trigeminal subnucleus caudalis and bulbar lateral reticular formation, Advanc. Pain Res. Ther., 3 (1979) 211-217.