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Contralateral mirror-image pain following anterolateral cordotomy
63
Pain, 88 (1988) 63-65 Elsevier
PA1 01206
Contralateral mirror-image pain following anterolateral cordotomy David Bowsher Pain Relief Foun~iion,
Department (Received
of neurological 4 September
Sciences, ~niuersit~ of Liverpool, Liverpool L9 IA E (U.K.)
1987, accepted
21 December
1987)
A h~othesis is put forward to explain the occurrence of moor-image pain following pain relief by anterolateral cordotomy. This depends upon the fact that some nociceptive neurones in the deep spinal grey matter have biiaterally symmetrical receptive fields, one-half of which is normally subject to tonic descending inhibitory control. It is suggested that some cordotomy lesions may damage this descending inhibitory pathway. Experience following naloxone injection in our own cases further suggests that this inhibitory mechanism may normally involve enkephalinergic intemeurones.
Sag
Key work
Mirror-image
pain;
Cordotomy
Introduction
satisfactory, and so have been led to re-examine the problem.
When anterolateral cordotomy has been carried out for the relief of unilateral pain, it is not uncommon to observe that patients subsequently report pain somewhere in the previously painless half of the body. This has been reported following cordotomy performed by both open surgical and percut~~us methods [e.g., 6,121. In the vast majority of cases, the new post-cordotomy pain is experienced in the mirror-image area contralateral to that in which pain was experienced prior to cordotomy [lo]. A number of explanations have been put forward to account for this phenomenon, ranging from patients’ reputed ‘need’ to feel pain through previously unnoticed pain to referral of sensation from the originally painful area. We have been unable to regard any of these explanations as
Correspondence to: Dr. David Bowsher, Pain Relief Foundation, Rice Lane, Liverpool L9 lAE, U.K. 0304-3959/88/$03.50
0 1988 Elsevier Science Publishers
Patients, procedures and results Thirteen patients who were subjected to percutaneous cervical cordotomy [6] were studied. All patients had satisfactory relief of unilateral pain. After careful clinical examination and mapping of the analgesic area, 3 patients were found to have pain in the mirror-image area on the side contralateral to the original pain for which cordotomy was performed. In 2 cases this ~ontra~ateral pain was mild, while in the other it was severe. All subjects were given 0.8 mg of naloxone by intravenous injection between 3 and 7 days after cordotomy. None were taking narcotic analgesics at the time of injection, nor had been for several days. One patient with mild boor-image pain experienced an exacerbation Iasting for 5 min, while the other did not. However, another patient, previously pain-free, felt contralateral mirror-
B.V. (Biomedical
Division)
PATIENTS,
CAUSE
.4ND SITE OF PAIN:
EFFEC.‘f
OF CORDOTOMY
Patient
Age
Cause of pain
Site of pain
Post-op.
M.K (f)
67
Ca L. pubic ramus
L. pubis
H.M (m) W.S(m) A.W (f) W.S(m) H.A (f) L.H (f) D.H (f) R.J (m) J.J (m)
61 77 60 62 51 73 69 66 46
Ca R. lung Asbestosis Pelvic Ca R. pancoast tumour Ca R. ovary Ca L. breast Ca cervix Ca bladder L. thigh leiomyosarcoma
R. R. R. R. R. L. L. R. L.
Immediate mirror-image pain R. knee Pam-free Pain-free Pain-free Pain-free Pain-free Pain-free Pain-free Pain-free Pain-free
J.M (f)
49
Ca L. ovary
L. leg
K.G (m) L.B(m)
70 50
Ca L. lung Ca L. lung
L. arm L. chest and shoulder
arm cheat buttock and leg arm loin elbow leg leg thigh and buttock
4ND
NALOXONL status
Immediate ‘slight’ pain R. leg Pain-free Immediate mirror-image pain R. shoulder
______ ..__ Pffect of 0.X mg naloxone
_._._-.. _
NII Felt ‘cold and nervous’ Nil Nil Nr1 Nil Felt dizzy; no pain Funny taste: no pain Nil Mirror-image pain R. buttock Exacerbated R. leg pain Nil Nil
(only)
image pain for a period of 5 min, beginning 10 min after injection. Details of the patient material are shown in Table I.
Discussion The notion that patients, often with malignant disease, whose pain is so severe that they seek surgical relief, subsequently feel so great a need for pain that they believe that they can feel it contralateral to the original pain which has been relieved by cordotomy, is so ludicrous as to merit little further discussion. It may simply be pointed out that when unilateral pain is relieved by narcotic drugs or procedures inflicted on peripheral nerves, such as ganglion blockade or rhizotomy, subsequent contralateral pain does not apparently occur. The explanation that a previously unnoticed pain subsequently impinges upon consciousness may also be dismissed, for it would be asking too much of coincidence to expect the great majority of such pains to occur in a site which is the mirror-image of that in which pain has been relieved by cordotomy.
That mirror-image pain is referred from the other side is indeed likely. But such a statement is a description, not an explanation. Spontaneous mirror-image pain, developing immediately following cordotomy or over the next few weeks, was observed in 17 out of 61 surgically cordotomised patients by Nathan [ll], and in 12 out of 33 percutaneously operated patients in the series recently supported by Nagaro et al. [9]; 3 of the 13 patients in the present study exhibited spontaneous mirror-image pain. Nathan [ll] has remarked that ‘painful, cold, or certain other sorts of stimuli applied to the part of the body rendered analgesic’ bring on the contralateral pain. Nagaro et al. [9] have refined this by observing that pinching, but not pin-prick, in the analgesic area elicits the contralateral pain. It may be noted that pinching stimulates C polymodal nociceptors, while pin-prick activates only A6 primary afferents [3]. Nagaro et al. [9] reported that intrathecal blockade of nerve roots coming from the analgesic area abolishes the mirror-image pain. Taken together with the observations described in the preceding paragraph, this puts beyond doubt the fact
65
that mirror-image pain is caused by input from the analgesic side. Although primary afferents have been observed to terminate on the side of the cord contralateral to that on which they enter [4], this is unlikely to be the explanation of mirror-image pain, because if such fibres were responsible for mirror-image pain, there is no reason why it should not occur in the non-cordotomised patient. The most likely explanation for the referral would be to postulate the existence of cells in the spinal cord with a bilaterally symmetrical receptive field, projecting in the anterolateral funiculus, whose ipsilateral field is normally suppressed. There are in fact neurones with bilaterally symmetrical receptive fields in the deep spinal grey responding to noxious stimulation [8]. In the monkey they project chiefly to the lower brainstem reticular formation [5]; morphologically similar cells have been observed in the deep spinal grey in the adult human cord [l]. These neurones constitute the spinal part of the spino-reticulo-diencephalic system postulated to be the substrate of tissue-damage pain sensation [2]. It must be supposed that the ipsilateral field is normally suppressed by an ipsilateral tonic descending inhibitory pathway, such as has been described by a number of authors (see review by Lundberg [7]). It may be supposed that in some cases, this descending inhibitory pathway is damaged by the cordotomy lesion, thus releasing the ipsilateral field and allowing the referral of pain sensation caused by contralateral input. It must further be presumed that the descending inhibitory fibres must lie either dorsal or medial to the ascending anterolateral pathway which is destroyed by anterolateral cordotomy. Such anatomy would explain why mirror-image pain only occurs in some and not all cases of cordotomy due to slight variability of the extent of the lesion within the cord. The finding reported herein that naloxone injection may briefly elicit or exacerbate mirror-image pain suggests that the inhibitory mechanism may be opioidergic, perhaps being
mediated by enkephalinergic intemeurones in the cord; small numbers of such cells have been reported in the deeper layers.
Acknowledgements The author is grateful to Dr. S. Lipton for permission to study his patients. A preliminary report on this work was presented to the Second World Congress on Pain, Montreal, 1978.
References 1 Abdel-Maguid, T.E. and Bowsher, D., The grey matter of the dorsal horn of the adult human spinal cord, including comparisons with general somatic and visceral cranial nerve nuclei, J. Anat. (Lond.), 142 (1985) 33-58. 2 Bowsher, D., The central pain pathway in man: the conscious appreciation of pain, Brain, 80 (1957) 606-622. 3 Bowsher, D., Role of the reticular formation in response to noxious stimulation, Pain, 2 (1976) 361-378. 4 Culberson, J.L., Haines, D.E., Kimmel, D.L. and Brown, P.B., Contralateral projection of primary afferent fibers to mammalian spinal cord, Exp. Neurol., 64 (1979) 83-97. 5 Kevetter, G.A. Haber, L.H., Yezierski, R.P., Chung, J.M., Martin, R.F. and Willis, W.D., Cells of origin of the spinoreticular tract in the monkey, J. Comp. Neurol., 207 (1982) 61-74. 6 Lipton, S., Percutaneous cervical cordotomy. In: J.J. Bonica and V. Ventafridda (Eds.), Adv. in Pain Res. Ther., Vol. 2, Raven Press, New York, 1979, pp. 425-438. 7 Lundberg, A., Control of spinal mechanisms from the brain. In: D.B. Tower (Ed.), The Nervous System. Vol. I. The Basic Neurosciences, Raven Press, New York, 1975, pp. 253-265. 8 Molinari, H., The cutaneous sensitivity of units in laminae VII and VIII of the cat, Brain Res., 234 (1982) 165-169. 9 Nagaro, T., Kimura, S. and Arai, T., A mechanism of new pain following cordotomy: reference of sensation, Pain, 30 (1987) 89-92. 10 Nathan, P.W., Reference of sensation at the spinal level, J. Neurol. Neurosurg. Psychiat., 19 (1956) 88-100. 11 Nathan, P.W., Results of antero-lateral cordotomy for pain in cancer, J. Neurol. Neurosurg. Psychiat.. 26 (1963) 353-362. 12 White, J.C. and Sweet, W.H., Pain, Thomas, Springfield, IL. 1955.
Pain, 88 (1988) 63-65 Elsevier
PA1 01206
Contralateral mirror-image pain following anterolateral cordotomy David Bowsher Pain Relief Foun~iion,
Department (Received
of neurological 4 September
Sciences, ~niuersit~ of Liverpool, Liverpool L9 IA E (U.K.)
1987, accepted
21 December
1987)
A h~othesis is put forward to explain the occurrence of moor-image pain following pain relief by anterolateral cordotomy. This depends upon the fact that some nociceptive neurones in the deep spinal grey matter have biiaterally symmetrical receptive fields, one-half of which is normally subject to tonic descending inhibitory control. It is suggested that some cordotomy lesions may damage this descending inhibitory pathway. Experience following naloxone injection in our own cases further suggests that this inhibitory mechanism may normally involve enkephalinergic intemeurones.
Sag
Key work
Mirror-image
pain;
Cordotomy
Introduction
satisfactory, and so have been led to re-examine the problem.
When anterolateral cordotomy has been carried out for the relief of unilateral pain, it is not uncommon to observe that patients subsequently report pain somewhere in the previously painless half of the body. This has been reported following cordotomy performed by both open surgical and percut~~us methods [e.g., 6,121. In the vast majority of cases, the new post-cordotomy pain is experienced in the mirror-image area contralateral to that in which pain was experienced prior to cordotomy [lo]. A number of explanations have been put forward to account for this phenomenon, ranging from patients’ reputed ‘need’ to feel pain through previously unnoticed pain to referral of sensation from the originally painful area. We have been unable to regard any of these explanations as
Correspondence to: Dr. David Bowsher, Pain Relief Foundation, Rice Lane, Liverpool L9 lAE, U.K. 0304-3959/88/$03.50
0 1988 Elsevier Science Publishers
Patients, procedures and results Thirteen patients who were subjected to percutaneous cervical cordotomy [6] were studied. All patients had satisfactory relief of unilateral pain. After careful clinical examination and mapping of the analgesic area, 3 patients were found to have pain in the mirror-image area on the side contralateral to the original pain for which cordotomy was performed. In 2 cases this ~ontra~ateral pain was mild, while in the other it was severe. All subjects were given 0.8 mg of naloxone by intravenous injection between 3 and 7 days after cordotomy. None were taking narcotic analgesics at the time of injection, nor had been for several days. One patient with mild boor-image pain experienced an exacerbation Iasting for 5 min, while the other did not. However, another patient, previously pain-free, felt contralateral mirror-
B.V. (Biomedical
Division)
PATIENTS,
CAUSE
.4ND SITE OF PAIN:
EFFEC.‘f
OF CORDOTOMY
Patient
Age
Cause of pain
Site of pain
Post-op.
M.K (f)
67
Ca L. pubic ramus
L. pubis
H.M (m) W.S(m) A.W (f) W.S(m) H.A (f) L.H (f) D.H (f) R.J (m) J.J (m)
61 77 60 62 51 73 69 66 46
Ca R. lung Asbestosis Pelvic Ca R. pancoast tumour Ca R. ovary Ca L. breast Ca cervix Ca bladder L. thigh leiomyosarcoma
R. R. R. R. R. L. L. R. L.
Immediate mirror-image pain R. knee Pam-free Pain-free Pain-free Pain-free Pain-free Pain-free Pain-free Pain-free Pain-free
J.M (f)
49
Ca L. ovary
L. leg
K.G (m) L.B(m)
70 50
Ca L. lung Ca L. lung
L. arm L. chest and shoulder
arm cheat buttock and leg arm loin elbow leg leg thigh and buttock
4ND
NALOXONL status
Immediate ‘slight’ pain R. leg Pain-free Immediate mirror-image pain R. shoulder
______ ..__ Pffect of 0.X mg naloxone
_._._-.. _
NII Felt ‘cold and nervous’ Nil Nil Nr1 Nil Felt dizzy; no pain Funny taste: no pain Nil Mirror-image pain R. buttock Exacerbated R. leg pain Nil Nil
(only)
image pain for a period of 5 min, beginning 10 min after injection. Details of the patient material are shown in Table I.
Discussion The notion that patients, often with malignant disease, whose pain is so severe that they seek surgical relief, subsequently feel so great a need for pain that they believe that they can feel it contralateral to the original pain which has been relieved by cordotomy, is so ludicrous as to merit little further discussion. It may simply be pointed out that when unilateral pain is relieved by narcotic drugs or procedures inflicted on peripheral nerves, such as ganglion blockade or rhizotomy, subsequent contralateral pain does not apparently occur. The explanation that a previously unnoticed pain subsequently impinges upon consciousness may also be dismissed, for it would be asking too much of coincidence to expect the great majority of such pains to occur in a site which is the mirror-image of that in which pain has been relieved by cordotomy.
That mirror-image pain is referred from the other side is indeed likely. But such a statement is a description, not an explanation. Spontaneous mirror-image pain, developing immediately following cordotomy or over the next few weeks, was observed in 17 out of 61 surgically cordotomised patients by Nathan [ll], and in 12 out of 33 percutaneously operated patients in the series recently supported by Nagaro et al. [9]; 3 of the 13 patients in the present study exhibited spontaneous mirror-image pain. Nathan [ll] has remarked that ‘painful, cold, or certain other sorts of stimuli applied to the part of the body rendered analgesic’ bring on the contralateral pain. Nagaro et al. [9] have refined this by observing that pinching, but not pin-prick, in the analgesic area elicits the contralateral pain. It may be noted that pinching stimulates C polymodal nociceptors, while pin-prick activates only A6 primary afferents [3]. Nagaro et al. [9] reported that intrathecal blockade of nerve roots coming from the analgesic area abolishes the mirror-image pain. Taken together with the observations described in the preceding paragraph, this puts beyond doubt the fact
65
that mirror-image pain is caused by input from the analgesic side. Although primary afferents have been observed to terminate on the side of the cord contralateral to that on which they enter [4], this is unlikely to be the explanation of mirror-image pain, because if such fibres were responsible for mirror-image pain, there is no reason why it should not occur in the non-cordotomised patient. The most likely explanation for the referral would be to postulate the existence of cells in the spinal cord with a bilaterally symmetrical receptive field, projecting in the anterolateral funiculus, whose ipsilateral field is normally suppressed. There are in fact neurones with bilaterally symmetrical receptive fields in the deep spinal grey responding to noxious stimulation [8]. In the monkey they project chiefly to the lower brainstem reticular formation [5]; morphologically similar cells have been observed in the deep spinal grey in the adult human cord [l]. These neurones constitute the spinal part of the spino-reticulo-diencephalic system postulated to be the substrate of tissue-damage pain sensation [2]. It must be supposed that the ipsilateral field is normally suppressed by an ipsilateral tonic descending inhibitory pathway, such as has been described by a number of authors (see review by Lundberg [7]). It may be supposed that in some cases, this descending inhibitory pathway is damaged by the cordotomy lesion, thus releasing the ipsilateral field and allowing the referral of pain sensation caused by contralateral input. It must further be presumed that the descending inhibitory fibres must lie either dorsal or medial to the ascending anterolateral pathway which is destroyed by anterolateral cordotomy. Such anatomy would explain why mirror-image pain only occurs in some and not all cases of cordotomy due to slight variability of the extent of the lesion within the cord. The finding reported herein that naloxone injection may briefly elicit or exacerbate mirror-image pain suggests that the inhibitory mechanism may be opioidergic, perhaps being
mediated by enkephalinergic intemeurones in the cord; small numbers of such cells have been reported in the deeper layers.
Acknowledgements The author is grateful to Dr. S. Lipton for permission to study his patients. A preliminary report on this work was presented to the Second World Congress on Pain, Montreal, 1978.
References 1 Abdel-Maguid, T.E. and Bowsher, D., The grey matter of the dorsal horn of the adult human spinal cord, including comparisons with general somatic and visceral cranial nerve nuclei, J. Anat. (Lond.), 142 (1985) 33-58. 2 Bowsher, D., The central pain pathway in man: the conscious appreciation of pain, Brain, 80 (1957) 606-622. 3 Bowsher, D., Role of the reticular formation in response to noxious stimulation, Pain, 2 (1976) 361-378. 4 Culberson, J.L., Haines, D.E., Kimmel, D.L. and Brown, P.B., Contralateral projection of primary afferent fibers to mammalian spinal cord, Exp. Neurol., 64 (1979) 83-97. 5 Kevetter, G.A. Haber, L.H., Yezierski, R.P., Chung, J.M., Martin, R.F. and Willis, W.D., Cells of origin of the spinoreticular tract in the monkey, J. Comp. Neurol., 207 (1982) 61-74. 6 Lipton, S., Percutaneous cervical cordotomy. In: J.J. Bonica and V. Ventafridda (Eds.), Adv. in Pain Res. Ther., Vol. 2, Raven Press, New York, 1979, pp. 425-438. 7 Lundberg, A., Control of spinal mechanisms from the brain. In: D.B. Tower (Ed.), The Nervous System. Vol. I. The Basic Neurosciences, Raven Press, New York, 1975, pp. 253-265. 8 Molinari, H., The cutaneous sensitivity of units in laminae VII and VIII of the cat, Brain Res., 234 (1982) 165-169. 9 Nagaro, T., Kimura, S. and Arai, T., A mechanism of new pain following cordotomy: reference of sensation, Pain, 30 (1987) 89-92. 10 Nathan, P.W., Reference of sensation at the spinal level, J. Neurol. Neurosurg. Psychiat., 19 (1956) 88-100. 11 Nathan, P.W., Results of antero-lateral cordotomy for pain in cancer, J. Neurol. Neurosurg. Psychiat.. 26 (1963) 353-362. 12 White, J.C. and Sweet, W.H., Pain, Thomas, Springfield, IL. 1955.