- Email: [email protected]
Behavioral evidence for a crossed ascending pathway for pain transmission in the anterolateral quadrant of the rat spinal cord
164
Brain Research, 376 (1986) 164-168
Elsevier BRE21576
Behavioral evidence for a crossed ascending pathway for pain transmission in the anterolateral quadrant of the rat spinal cord MARC PESCHANSKI, VALI~RIEKAYSER and JEAN-MARIE BESSON Unit~ de Recherches de Neurophysiologie Pharmacologique, INSERM U 161, Paris 75014 (France)
(Accepted February llth, 1986) Key words: pain pathway- - noxious test - - vocalization- - anterolateral quadrant - - spinal cord
Thresholds of two behavioral responses to noxious pressure of the hindpaws (withdrawal, vocalization) were analyzed before and 3 weeks after a lesion of various quadrants of the spinal cord at the cervical level. The threshold of the spinal reflex could not be modified. Threshold of vocalization elicited by the pressure of one hindpaw was significantlyincreased when, and only when, the opposite ventrolateral quadrant was cut. These results emphasize the role of the lateral spinothalamic tract in the transmission of noxious messages.
Since the demonstration by Spiller 15 that an anterolateral cordotomy induced hypoalgesia in the opposite subjacent part of the body, numerous clinical data have confirmed that, in man, the fiber tracts contained in this portion of the spinal cord white matter are necessary for the sensori-discriminative aspects of pain sensation 1°,19. Neurosurgeons have used this knowledge to relieve clinical pain by anterolateral cordotomy. Various clinical and experimental findings are, however, in contrast to such a strict association of the pain transmission system with a crossed ascending pathway in the anterolateral quadrant of the spinal cord. Wall and Noordenbos 18have indicated that the preservation of only one anterolateral quadrant permitted not only the perception of pain but also that of crude somesthetic stimuli. As reviewed by White and Sweet a9, neurosurgeons have achieved long-lasting relief of chronic pain after a verified anterolateral cordotomy in only 50% of cases. Behavioral experiments in several species have repeatedly failed to demonstrate a hypoalgesic effect of a unilateral anterolateral cordotomy on various reactions to noxious stimuli 1&16'17. All these authors claimed that a bilateral cordotomy was necessary and proposed that sev-
eral pathways could in fact be available for pain transmission. This hypothesis of multiple complementary ascending pathways in the spinal cord was supported by the demonstration in electrophysiological studies that many ascending pathways have their origin in noxious-responsive neurons (see refs. in refs. 2 and 20). The present study has therefore been undertaken to reassess systematically the effects of lesions of various portions of the white matter of the spinal cord upon behavioral reactions elicited by a noxious mechanical stimulus applied with a pressure algometer 14'21. The use of such a procedure allowed us to analyse simultaneously the threshold of responses to noxious stimulation on a spinal reflex (withdrawal of the limb), and a centrally processed reaction (vocalization). In addition, it was possible to compare the responses obtained by pressing successively on each side, permitting a definition of a lateralization of the effect of a particular lesion. Thirty-nine male Sprague-Dawley albino rats, weighing 200-225 g at the beginning of the experiments, were used. Using the Basile analgesymeter (Apelex), thresholds for reflex withdrawal of the limb and for vocalization were determined by apply-
Correspondence: M. Peschanski, Unit6 de Recherches de NeurophysiologiePharmacologique, INSERM U 161, 2 rue d'A16sia, Paris
75014, France. 0006-8993/86/$03.50© 1986Elsevier Science Publishers B.V. (BiomedicalDivision)
165 ing increasing pressure, successively, to each hindpaw. For each rat, preliminary threshold determinations were carried out before the surgery was performed, and two consecutive stable thresholds obtained for both hindpaws. Under chloral hydrate (400 mg/kg) anesthesia,
various lesions of the cord were produced using a sharp blade (no. 11) or a lancet diamond knife (A. Meyer Co.) at the level of the C5 vertebra (Fig. 1). In 8 other cases, laminectomy either of the first and second cervical (n = 4) or of the first and second lumbar vertebrae (n = 4) was performed and a longitudinal
Fig. 1. Photomicrographs of Nissl-stained sections showing spinal lesions. From top left, photomicrographs correspond respectively to cases no. 10, 5, 12 and 2 illustrated in Fig. 3 and to two commissurotomies performed, respectively, at the cervical and at the lumbar levels.
166 p o r t i o n of the anterior column. In addition to these 12 cases, no alteration in vocalization threshold was o b s e r v e d in the 4 animals in which a high cervical c o m m i s s u r o t o m y was p e r f o r m e d . It can be n o t e d that in these cases of cervical c o m m i s s u r o t o m y , the anteromedial tracts could also be e n c r o a c h e d without inducing an alteration of the vocalization threshold. In 18 cases, a consistent increase in the vocalization thresholds was o b s e r v e d (Fig. 3). This effect was unilateral in 14 cases and bilateral in the 4 cases of l u m b a r commissurotomy. In all cases of unilateral effect,the lesion touched the anterolateral q u a d r a n t opposite to the side of the behavioral change, either cutting it completely or encroaching upon its lateral or medial parts. This q u a d r a n t was the only area systematically r e a c h e d by the lesion. W h e n l u m b a r commissurotomies were p e r f o r m e d , increases in the thresholds of vocalization were p r o n o u n c e d on both sides, reaching 'cut-off' (500 g) in almost half of the cases. It can be n o t e d that this alteration is most p r o b a b l y related to the interruption of crossing fibers since no additional lesion of the anterolateral columns could be o b s e r v e d in two of these cases of lumbar commissurotomies. The present study has d e m o n s t r a t e d that a partial lesion of the spinal cord involving one anterolateral
cut m a d e , using the d i a m o n d knife, in o r d e r to obtain a complete commissurotomy. In 5 rats, the d u r a was simply o p e n e d , and no cut p e r f o r m e d in the cord. The thresholds of responses to noxious pressure were d e t e r m i n e d again for each rat following the same protocol, 3 weeks after surgery. Then, the animals received an overdose of sodium p e n t o b a r b i t a l and were perfused transcardially with saline followed by formalin. The spinal cord was r e m o v e d and cut at 100/~m thickness for Nissl-staining using Cresyl violet. Superimposition of c a m e r a lucida drawings of successive sections containing the lesion site allowed the complete extent of the section to be d e t e r m i n e d . Before surgery, the withdrawal and the vocalization thresholds were similar from one animal to the other and for both paws in each rat (see Figs. 2 and 3). W i t h d r a w a l thresholds were a r o u n d 100-120 g and vocalization thresholds a r o u n d 200-250 g. A f t e r surgery, withdrawal thresholds r e m a i n e d systematically c o m p a r a b l e to controls, irrespective of the effect of the lesion on the vocalization thresholds. Vocalization thresholds were not altered in the 5 control animals which had received no spinal cuts and in 12 o t h e r cases which are p r e s e n t e d in Fig. 2. In these cases, ineffective lesions were those of the dorsal columns, the dorsolateral a r e a and the medial
I'
2'
:3'
4'
before lesion
200
220
240
230
220
210
3wks after
230
250
240
240
210
210
7"
8"
'before lesion
230
240
3wks after
220
230
200
230
240
210
240
230
250
230
210
9'
5"
240
220
220
10' 240
260
250
300
6' 200
230
200
230
240
220'
I1'
12'
240
210
240
230
240
250
230
240
200
240
Fig. 2. Behavioral results obtained after spinal lesions: cases in which the lesion failed to modify the thresholds of responses to hindpaw pressure. In this and in Fig. 3, each case, indicated by a number, is illustrated by a composite camera lucida drawing showing (in black) the lesioned area. Thresholds of the vocalization responses are indicated on the left for the pressure of the left hindpaw and on the right for the right hindpaw, before the lesion on the line above the drawing and 3 weeks after below it. Values are in grams.
167
2
3
I
before lesion
240
240
220
230
230
240
220
240
250
230
3 wks after
500
280
400
250
280
480
480
270
500
220
7
8
9
10
6 220
r
260
440
I!
240
12
before lesion
230
240
230
240
210
230
210
230
220
240
i 230
250
3 wks after
300
460
500
300
220
440
500
200
400
240
460
230
13 before ilesio n
250
14 250
~ )
3 wks after
500
220
(
300
430
15 250
230
16 250
~
240
17 240
LUMBAR
240
500
500
500
240
18 250
220
230
500
500
COMMISSUROTOMY
480
440
470
Fig. 3. Behavioral results obtained after spinal lesions: cases in which the lesion modified the thresholds of the vocalization responses. See Fig. 2 for explanation.
quadrant increases the threshold of the vocalization induced by a noxious pressure. The present results also indicate that the spinal ascending pathway responsible for this response is mostly, if not exclusively, crossed. It has also demonstrated that the pathway crosses the midline at the lumbar level (when hindpaw pressure is considered), i.e. immediately after the spinal relay. The present data therefore strongly favor a privileged role for the lateral spinothalamic pathway (the spinothalamic fibers which project to the lateral thalamus) since this pathway is completely crossed in the rat 8,9,13,22 and travels in the anterolateral quadrant of the spinal cord 6. These results are in agreement with the repeated demonstration that anterolateral cordotomies in humans produce hypo- or analgesia in the subjacent territory of the opposite side of the body 1°. Moreover, the good therapeutic results obtained after anterior commissurotomies can also be explained by the existence of such a crossed pain-pathway 7,12.
The present data differ from the results of previous behavioral studies where effects of lesions of the spinal cord upon nocifensive responses were studied. Indeed in the rat 1, as in other species 3'16'17, it was observed that a bilateral lesion of the anterolateral quadrants of the spinal cord was necessary to obtain an increase in threshold of various pain-elicited reactions. One explanation of this discrepancy could be the use, in most previous studies, of electrical shocks to elicit pain-related behaviors while we have used a natural noxious mechanical stimulation. Indeed, it has been demonstrated in humans 11 that the analgesic areas produced after cordotomy were more reduced when determined using electrical stimuli to obtain the pain threshold, than when established through usual clinical means. In some cases, analgesia studied with electrical shocks was incomplete in patients in whom clinical results were successful. Thus it is likely that electrical shocks and noxious mechanical stimuli activate the pain systems differ-
168 ently. Indeed, an electrical shock will activate my-
Comparison of results of experiments combining the
elinated (A) fibers at an intensity much lower than
determination of vocalization thresholds by electrical
that required for the activation of u n m y e l i n a t e d (C) fibers 5. The pain-reaction threshold would therefore likely be that of the activation of A 6 nociceptors (see refs. in refs. 2 and 4). F u r t h e r m o r e , such an electrical
and noxious mechanical stimulation in the same animals would be helpful to further consider this prob-
stimulation would have also recruited most non-noci-
The authors are indebted to D r J. Leah for his help with the language. Supported by the Institut de la
ceptive large-diameter fibers, which might alter the transmission of noxious inputs at the spinal level.
1 Basbaum, A.I., Conduction of the effects of noxious stimulation by short-fiber multisynaptic systems of the spinal cord in the rat, Exp. Neurol., 40 (1973) 699-716. 2 Besson, J.M., Guilbaud, G., Abdelmoum6ne, M. and Chaouch, A., Physiologie de la nociception, J. Physiol. (Paris), 78 (1982) 7-107. 3 Breazile, J.E. and Kitchell, R.L., A study of fiber systems within the spinal cord of the domestic guinea pig that subserve pain, J. Comp. Neurol., 133 (1968) 373-382. 4 Burgess, P.R. and Perl, E.R., Cutaneous mechanoreceptors and nociceptors. In A. Iggo (Ed.), Handbook of Sensory Physiology, Vol. II: Somatosensory System, Springer, Berlin, 1972, pp. 29-78. 5 Gasser, H.S. and Erlanger, J., The role played by the sizes of the constituent fibers of a nerve trunk in determining the form of its action potential wave, Am. J. Physiol., 80 (1927) 522-547. 6 Giesler, G.J., Jr., Spiel, H.R. and Willis, W.D., Organization of spinothalamic tract axons within the rat spinal cord, J. Comp. Neurol., 195 (1981) 243-252. 7 King, R.B., Anterior commissurotomy for intractable pain, J. Neurosurg., 47 (1977) 7-11. 8 Lund, R.D. and Webster, K.E., Thalamic afferents from the spinal cord and the trigeminal nuclei. An experimental anatomical study in the rat, J. Comp. Neurol., 130 (1967) 313-328. 9 Mehler, W.R., Some anatomical species differences. A posteriori, Ann. N. Y. Acad. Sci., 167 (1969) 424-468. 10 Nathan, P.W. and Smith, M., Clinicoanatomical correlation in anterolateral cordotomy. In J.J. Bonica (Ed.), Advances in Pain Research Ther., Vol. 3, Raven Press, New York, 1979, pp. 921-925. 11 Papo, I. and Caruselli, G., Le seuil de la sensibilit6 douloureuse apr6s cordotomie spinothalamique, Neuro-Chir. (Paris), 16 (1970) 513-524. 12 Papo, I. and Luongo, A., High cervical commissural myelotomy in the treatment of pain, J. Neurol. Neurosurg. Psychiat., 39 (1976) 705-710.
lem.
Sant6 et de la Rechercher M6dicale.
13 Peschanski, M., Mantyh, P.W. and Besson, J.M., Spinal afferents to the ventrobasal complex of the rat thalamus, Brain Research, 287 (1983) 240-244. 14 Randall, L.O. and Selitto, J.J., A method for measurement of analgesic activity of inflammed tissue, Arch. Int. Pharmacodyn., 61 (1957) 409-419. 15 Spiller, W.G., The occasional clinical resemblance between caries of the vertebrae and lumbothoracic syringomyelia, and the location within the spinal cord of the fibres for the sensation of pain and temperature, Univ. Penn. Med. Bull., 18 (1905) 147-154. 16 Vierck, C.J., Jr. and Luck, M.M., Loss and recovery of reactivity to noxious stimuli in monkeys with primary spinothalamic cordotomies, followed by secondary and tertiary lesions of other cord sectors, Brain, 102 (1979) 233-248. 17 Vierck, C.J., Cooper, B.Y., Franzen, D., Ritz, L.A. and Greenspan, J.D., Behavioral analysis of CNS pathways and transmitter systems involved in conduction and inhibition of pain sensations and reactions in primates. In J. Sprague and A. Epstein (Eds.), Progress in Psychobiology, Vol. 10, Academic Press, New York, 1983, pp. 113-165. 18 Wall, P.D. and Noordenbos, W., Sensory functions which remain in man after complete transection of dorsal columns, Brain, 100 (1977) 641-653. 19 White, J.C. and Sweet, W.H., Pain and The Neurosurgeon: A Forty Year Experience, C.C. Thomas, Springfield, IL, 1969. 20 Willis, W.D. and Coggeshall, R.E., Sensory Mechanims of The Spinal Cord, Plenum Press, New York, 1978, 485 pp. 21 Winter, C.A. and Flataker, L., Reaction thresholds to pressure in oedematous hindpaws of rats responses to analgesic drugs, J. Pharmacol. Exp. Ther., 150 (1963) 165-171. 22 Zemlan, F.P., Leonard, C.M., Kow, L.M. and Pfaff, D.W., Ascending tracts of the lateral columns of the rat spinal cord: a study using the silver impregnation and horseradish peroxidase techniques, Exp. Neurol., 62 (1978) 298-334.
Brain Research, 376 (1986) 164-168
Elsevier BRE21576
Behavioral evidence for a crossed ascending pathway for pain transmission in the anterolateral quadrant of the rat spinal cord MARC PESCHANSKI, VALI~RIEKAYSER and JEAN-MARIE BESSON Unit~ de Recherches de Neurophysiologie Pharmacologique, INSERM U 161, Paris 75014 (France)
(Accepted February llth, 1986) Key words: pain pathway- - noxious test - - vocalization- - anterolateral quadrant - - spinal cord
Thresholds of two behavioral responses to noxious pressure of the hindpaws (withdrawal, vocalization) were analyzed before and 3 weeks after a lesion of various quadrants of the spinal cord at the cervical level. The threshold of the spinal reflex could not be modified. Threshold of vocalization elicited by the pressure of one hindpaw was significantlyincreased when, and only when, the opposite ventrolateral quadrant was cut. These results emphasize the role of the lateral spinothalamic tract in the transmission of noxious messages.
Since the demonstration by Spiller 15 that an anterolateral cordotomy induced hypoalgesia in the opposite subjacent part of the body, numerous clinical data have confirmed that, in man, the fiber tracts contained in this portion of the spinal cord white matter are necessary for the sensori-discriminative aspects of pain sensation 1°,19. Neurosurgeons have used this knowledge to relieve clinical pain by anterolateral cordotomy. Various clinical and experimental findings are, however, in contrast to such a strict association of the pain transmission system with a crossed ascending pathway in the anterolateral quadrant of the spinal cord. Wall and Noordenbos 18have indicated that the preservation of only one anterolateral quadrant permitted not only the perception of pain but also that of crude somesthetic stimuli. As reviewed by White and Sweet a9, neurosurgeons have achieved long-lasting relief of chronic pain after a verified anterolateral cordotomy in only 50% of cases. Behavioral experiments in several species have repeatedly failed to demonstrate a hypoalgesic effect of a unilateral anterolateral cordotomy on various reactions to noxious stimuli 1&16'17. All these authors claimed that a bilateral cordotomy was necessary and proposed that sev-
eral pathways could in fact be available for pain transmission. This hypothesis of multiple complementary ascending pathways in the spinal cord was supported by the demonstration in electrophysiological studies that many ascending pathways have their origin in noxious-responsive neurons (see refs. in refs. 2 and 20). The present study has therefore been undertaken to reassess systematically the effects of lesions of various portions of the white matter of the spinal cord upon behavioral reactions elicited by a noxious mechanical stimulus applied with a pressure algometer 14'21. The use of such a procedure allowed us to analyse simultaneously the threshold of responses to noxious stimulation on a spinal reflex (withdrawal of the limb), and a centrally processed reaction (vocalization). In addition, it was possible to compare the responses obtained by pressing successively on each side, permitting a definition of a lateralization of the effect of a particular lesion. Thirty-nine male Sprague-Dawley albino rats, weighing 200-225 g at the beginning of the experiments, were used. Using the Basile analgesymeter (Apelex), thresholds for reflex withdrawal of the limb and for vocalization were determined by apply-
Correspondence: M. Peschanski, Unit6 de Recherches de NeurophysiologiePharmacologique, INSERM U 161, 2 rue d'A16sia, Paris
75014, France. 0006-8993/86/$03.50© 1986Elsevier Science Publishers B.V. (BiomedicalDivision)
165 ing increasing pressure, successively, to each hindpaw. For each rat, preliminary threshold determinations were carried out before the surgery was performed, and two consecutive stable thresholds obtained for both hindpaws. Under chloral hydrate (400 mg/kg) anesthesia,
various lesions of the cord were produced using a sharp blade (no. 11) or a lancet diamond knife (A. Meyer Co.) at the level of the C5 vertebra (Fig. 1). In 8 other cases, laminectomy either of the first and second cervical (n = 4) or of the first and second lumbar vertebrae (n = 4) was performed and a longitudinal
Fig. 1. Photomicrographs of Nissl-stained sections showing spinal lesions. From top left, photomicrographs correspond respectively to cases no. 10, 5, 12 and 2 illustrated in Fig. 3 and to two commissurotomies performed, respectively, at the cervical and at the lumbar levels.
166 p o r t i o n of the anterior column. In addition to these 12 cases, no alteration in vocalization threshold was o b s e r v e d in the 4 animals in which a high cervical c o m m i s s u r o t o m y was p e r f o r m e d . It can be n o t e d that in these cases of cervical c o m m i s s u r o t o m y , the anteromedial tracts could also be e n c r o a c h e d without inducing an alteration of the vocalization threshold. In 18 cases, a consistent increase in the vocalization thresholds was o b s e r v e d (Fig. 3). This effect was unilateral in 14 cases and bilateral in the 4 cases of l u m b a r commissurotomy. In all cases of unilateral effect,the lesion touched the anterolateral q u a d r a n t opposite to the side of the behavioral change, either cutting it completely or encroaching upon its lateral or medial parts. This q u a d r a n t was the only area systematically r e a c h e d by the lesion. W h e n l u m b a r commissurotomies were p e r f o r m e d , increases in the thresholds of vocalization were p r o n o u n c e d on both sides, reaching 'cut-off' (500 g) in almost half of the cases. It can be n o t e d that this alteration is most p r o b a b l y related to the interruption of crossing fibers since no additional lesion of the anterolateral columns could be o b s e r v e d in two of these cases of lumbar commissurotomies. The present study has d e m o n s t r a t e d that a partial lesion of the spinal cord involving one anterolateral
cut m a d e , using the d i a m o n d knife, in o r d e r to obtain a complete commissurotomy. In 5 rats, the d u r a was simply o p e n e d , and no cut p e r f o r m e d in the cord. The thresholds of responses to noxious pressure were d e t e r m i n e d again for each rat following the same protocol, 3 weeks after surgery. Then, the animals received an overdose of sodium p e n t o b a r b i t a l and were perfused transcardially with saline followed by formalin. The spinal cord was r e m o v e d and cut at 100/~m thickness for Nissl-staining using Cresyl violet. Superimposition of c a m e r a lucida drawings of successive sections containing the lesion site allowed the complete extent of the section to be d e t e r m i n e d . Before surgery, the withdrawal and the vocalization thresholds were similar from one animal to the other and for both paws in each rat (see Figs. 2 and 3). W i t h d r a w a l thresholds were a r o u n d 100-120 g and vocalization thresholds a r o u n d 200-250 g. A f t e r surgery, withdrawal thresholds r e m a i n e d systematically c o m p a r a b l e to controls, irrespective of the effect of the lesion on the vocalization thresholds. Vocalization thresholds were not altered in the 5 control animals which had received no spinal cuts and in 12 o t h e r cases which are p r e s e n t e d in Fig. 2. In these cases, ineffective lesions were those of the dorsal columns, the dorsolateral a r e a and the medial
I'
2'
:3'
4'
before lesion
200
220
240
230
220
210
3wks after
230
250
240
240
210
210
7"
8"
'before lesion
230
240
3wks after
220
230
200
230
240
210
240
230
250
230
210
9'
5"
240
220
220
10' 240
260
250
300
6' 200
230
200
230
240
220'
I1'
12'
240
210
240
230
240
250
230
240
200
240
Fig. 2. Behavioral results obtained after spinal lesions: cases in which the lesion failed to modify the thresholds of responses to hindpaw pressure. In this and in Fig. 3, each case, indicated by a number, is illustrated by a composite camera lucida drawing showing (in black) the lesioned area. Thresholds of the vocalization responses are indicated on the left for the pressure of the left hindpaw and on the right for the right hindpaw, before the lesion on the line above the drawing and 3 weeks after below it. Values are in grams.
167
2
3
I
before lesion
240
240
220
230
230
240
220
240
250
230
3 wks after
500
280
400
250
280
480
480
270
500
220
7
8
9
10
6 220
r
260
440
I!
240
12
before lesion
230
240
230
240
210
230
210
230
220
240
i 230
250
3 wks after
300
460
500
300
220
440
500
200
400
240
460
230
13 before ilesio n
250
14 250
~ )
3 wks after
500
220
(
300
430
15 250
230
16 250
~
240
17 240
LUMBAR
240
500
500
500
240
18 250
220
230
500
500
COMMISSUROTOMY
480
440
470
Fig. 3. Behavioral results obtained after spinal lesions: cases in which the lesion modified the thresholds of the vocalization responses. See Fig. 2 for explanation.
quadrant increases the threshold of the vocalization induced by a noxious pressure. The present results also indicate that the spinal ascending pathway responsible for this response is mostly, if not exclusively, crossed. It has also demonstrated that the pathway crosses the midline at the lumbar level (when hindpaw pressure is considered), i.e. immediately after the spinal relay. The present data therefore strongly favor a privileged role for the lateral spinothalamic pathway (the spinothalamic fibers which project to the lateral thalamus) since this pathway is completely crossed in the rat 8,9,13,22 and travels in the anterolateral quadrant of the spinal cord 6. These results are in agreement with the repeated demonstration that anterolateral cordotomies in humans produce hypo- or analgesia in the subjacent territory of the opposite side of the body 1°. Moreover, the good therapeutic results obtained after anterior commissurotomies can also be explained by the existence of such a crossed pain-pathway 7,12.
The present data differ from the results of previous behavioral studies where effects of lesions of the spinal cord upon nocifensive responses were studied. Indeed in the rat 1, as in other species 3'16'17, it was observed that a bilateral lesion of the anterolateral quadrants of the spinal cord was necessary to obtain an increase in threshold of various pain-elicited reactions. One explanation of this discrepancy could be the use, in most previous studies, of electrical shocks to elicit pain-related behaviors while we have used a natural noxious mechanical stimulation. Indeed, it has been demonstrated in humans 11 that the analgesic areas produced after cordotomy were more reduced when determined using electrical stimuli to obtain the pain threshold, than when established through usual clinical means. In some cases, analgesia studied with electrical shocks was incomplete in patients in whom clinical results were successful. Thus it is likely that electrical shocks and noxious mechanical stimuli activate the pain systems differ-
168 ently. Indeed, an electrical shock will activate my-
Comparison of results of experiments combining the
elinated (A) fibers at an intensity much lower than
determination of vocalization thresholds by electrical
that required for the activation of u n m y e l i n a t e d (C) fibers 5. The pain-reaction threshold would therefore likely be that of the activation of A 6 nociceptors (see refs. in refs. 2 and 4). F u r t h e r m o r e , such an electrical
and noxious mechanical stimulation in the same animals would be helpful to further consider this prob-
stimulation would have also recruited most non-noci-
The authors are indebted to D r J. Leah for his help with the language. Supported by the Institut de la
ceptive large-diameter fibers, which might alter the transmission of noxious inputs at the spinal level.
1 Basbaum, A.I., Conduction of the effects of noxious stimulation by short-fiber multisynaptic systems of the spinal cord in the rat, Exp. Neurol., 40 (1973) 699-716. 2 Besson, J.M., Guilbaud, G., Abdelmoum6ne, M. and Chaouch, A., Physiologie de la nociception, J. Physiol. (Paris), 78 (1982) 7-107. 3 Breazile, J.E. and Kitchell, R.L., A study of fiber systems within the spinal cord of the domestic guinea pig that subserve pain, J. Comp. Neurol., 133 (1968) 373-382. 4 Burgess, P.R. and Perl, E.R., Cutaneous mechanoreceptors and nociceptors. In A. Iggo (Ed.), Handbook of Sensory Physiology, Vol. II: Somatosensory System, Springer, Berlin, 1972, pp. 29-78. 5 Gasser, H.S. and Erlanger, J., The role played by the sizes of the constituent fibers of a nerve trunk in determining the form of its action potential wave, Am. J. Physiol., 80 (1927) 522-547. 6 Giesler, G.J., Jr., Spiel, H.R. and Willis, W.D., Organization of spinothalamic tract axons within the rat spinal cord, J. Comp. Neurol., 195 (1981) 243-252. 7 King, R.B., Anterior commissurotomy for intractable pain, J. Neurosurg., 47 (1977) 7-11. 8 Lund, R.D. and Webster, K.E., Thalamic afferents from the spinal cord and the trigeminal nuclei. An experimental anatomical study in the rat, J. Comp. Neurol., 130 (1967) 313-328. 9 Mehler, W.R., Some anatomical species differences. A posteriori, Ann. N. Y. Acad. Sci., 167 (1969) 424-468. 10 Nathan, P.W. and Smith, M., Clinicoanatomical correlation in anterolateral cordotomy. In J.J. Bonica (Ed.), Advances in Pain Research Ther., Vol. 3, Raven Press, New York, 1979, pp. 921-925. 11 Papo, I. and Caruselli, G., Le seuil de la sensibilit6 douloureuse apr6s cordotomie spinothalamique, Neuro-Chir. (Paris), 16 (1970) 513-524. 12 Papo, I. and Luongo, A., High cervical commissural myelotomy in the treatment of pain, J. Neurol. Neurosurg. Psychiat., 39 (1976) 705-710.
lem.
Sant6 et de la Rechercher M6dicale.
13 Peschanski, M., Mantyh, P.W. and Besson, J.M., Spinal afferents to the ventrobasal complex of the rat thalamus, Brain Research, 287 (1983) 240-244. 14 Randall, L.O. and Selitto, J.J., A method for measurement of analgesic activity of inflammed tissue, Arch. Int. Pharmacodyn., 61 (1957) 409-419. 15 Spiller, W.G., The occasional clinical resemblance between caries of the vertebrae and lumbothoracic syringomyelia, and the location within the spinal cord of the fibres for the sensation of pain and temperature, Univ. Penn. Med. Bull., 18 (1905) 147-154. 16 Vierck, C.J., Jr. and Luck, M.M., Loss and recovery of reactivity to noxious stimuli in monkeys with primary spinothalamic cordotomies, followed by secondary and tertiary lesions of other cord sectors, Brain, 102 (1979) 233-248. 17 Vierck, C.J., Cooper, B.Y., Franzen, D., Ritz, L.A. and Greenspan, J.D., Behavioral analysis of CNS pathways and transmitter systems involved in conduction and inhibition of pain sensations and reactions in primates. In J. Sprague and A. Epstein (Eds.), Progress in Psychobiology, Vol. 10, Academic Press, New York, 1983, pp. 113-165. 18 Wall, P.D. and Noordenbos, W., Sensory functions which remain in man after complete transection of dorsal columns, Brain, 100 (1977) 641-653. 19 White, J.C. and Sweet, W.H., Pain and The Neurosurgeon: A Forty Year Experience, C.C. Thomas, Springfield, IL, 1969. 20 Willis, W.D. and Coggeshall, R.E., Sensory Mechanims of The Spinal Cord, Plenum Press, New York, 1978, 485 pp. 21 Winter, C.A. and Flataker, L., Reaction thresholds to pressure in oedematous hindpaws of rats responses to analgesic drugs, J. Pharmacol. Exp. Ther., 150 (1963) 165-171. 22 Zemlan, F.P., Leonard, C.M., Kow, L.M. and Pfaff, D.W., Ascending tracts of the lateral columns of the rat spinal cord: a study using the silver impregnation and horseradish peroxidase techniques, Exp. Neurol., 62 (1978) 298-334.