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Electrical control of facial pain
Electrical C. HUNTER SHELDEN, M.D.,
Control
of Facial
ROBERT
From the Repartment of Neurological Surgery, of Medical Research, Huntington Memorial Pasadena, California.
because of its selective permeability, maintains an internal resting state of - 70 mv. Any adequate stimulus, mechanical or electrical, acts first to lower the resting potential to an arbitrary level, possibly -45 mv., at which point for some unknown reason the membrane permeability to sodium ions suddenly increases and positive sodium ions pour through the membrane. Thus, once the restraining influence in the membane is reduced, these positive ions stream passively down their electrical and chemical gradient and lower the internal negative potential, not only to zero but even overshooting it, producing a momentary positive potential within the nerve fiber. This produces depolarization, in which state the nerve fiber is refractory. A second impulse cannot pass this point until ionic recovery has occurred and the previous resting potential of -70 mv. is again attained. It is at this point in the passage of a nerve impulse that we have focused our interest in the hope of reproducing such a refractory state intermittently or permanently in a portion of the fiber population of a nerve or its central projection. By so doing, we might prevent the normal process of recovery which is largely the result of extrusion of the sodium ions from the interior of the fiber by an active transport mechanism termed the sodium pump. We are conducting an in-depth study of electric and electromagnetic methods of altering or interrupting nervous function, but here we shall report only on our clinical results in patients with trigeminal neuralgia. The ultimate in the treatment of such a major neuralgia would be complete pain relief without associated sensory loss in the face. Such a result is theoretically possible, using the compression
Institute Hospital,
symptom which everyone understands but no one can accurately describe. It is likely that the subjective response to a given painful stimulus varies far more than the actual electrochemical impulses. This, no doubt, can be explained on the basis of the extremely complicated integration that occurs within the central nervous system. Our recent efforts have been directed toward electrical control of the recurrent paroxysmal pain in the face which constitutes the clinical syndrome described as trigeminal neuralgia. Implanted electrodes placed in the substance of the mandibular division of the trigeminal nerve appear to have been successful in controlling pain in three selected patients. The rationale of the method depends upon utilizing the refractory period in the nerve to prevent the passage of subsequent impulses. The passage of a nerve impulse is a complicated, not yet fully understood process which can be briefly summarized. A nerve fiber consists of axoplasm surrounded by a cylindric axon membrane which serves to separate the ions in the interstitial fluid from those within the nerve. The axoplasm has a negative resting potential (- 70 mv.) due chiefly to the presence of large negative organic ions, whereas outside the membrane there is a high concentration of positive sodium ions. In addition, there is a much higher concentration of potassium ions within the axoplasm. The net result of these plus other less significant ions is the creation of a chemical and electrical gradient across the membrane. The electrical gradient, however,
P
Pain*
AIN is a truly fascinating
* Presented at the Thirty-Eighth Annual Meeting of the Pacific Coast Surgical Association, Monterey, California, February 19-22, 1967. Vol.
114.
Aueust
1967
209
210
Shelden, Pudenz, and Doyle
operation which we developed in 1953 ; however, in practice it is
lator operating at 14 kc., housed in a standard flashlight case. The transmitter replaces the light and reflector assembly. The unit, when energized, draws approximately 150 milliwatts of power. The implant unit, measuring 11/4 by “/8 inches, is encased in methyl methacrylate to protect the unit, allow sterilization, and facilitate attachment to the bony margins of the temporal craniotomy. It is an inductor receiver which consists of a 14 kc. resonate circuit which, when energized at a distance of “Is inch from the transmitter, is capable of providing a potential of 10 volts. We have employed this method with three patients with third division pain who have remained pain-free and without subjective or objective sensory loss since operation. The observation period has been four, three and a half, and three and a quarter years, respectively. Originally, our major concern was whether the method would function according to design. It seems apparent that the initial goal was achieved but, as time passes, we become less certain as to the specific factors responsible for the pain relief. In fact, the many unanswered questions have been responsible for our present research program. After implantation of the unit in the first patient, numerous studies were performed, including frequent activation of the electrodes, using the external power source. We had no idea how often the nerve should be actively depolarized ; hence, a daily schedule of activation was
carried out for several weeks despite the fact that the patient was experiencing no pain. Each time the power source was applied, numbness developed in the mandibular division lasting several minutes after the power was discontinued. After the first few weeks this procedure was discontinued. The second and third patients have never had the nerve actively depolarized, yet have remained equally asymptomatic. Naturally, from our experience with the compression operation we have considered that, possibly, we are merely traumatizing the third division fibers. This is unlikely since in 1951 we treated ten patients by decompression of the nerve at the foramen ovale using a dental burr, and within a period of one year the majority of the patients had had a return of pain; within two years, all had return of pain. Our other concerns are less easily decided. Is the receiving unit in some way being activated or is there actually a current flowing between two dissimilar electrodes? Both seem unlikely. Is the platinum acting as a catalyst in a local ionic reaction, producing a minute local current? The electrodes attached to the nerve were enclosed in silicone rubber which does have a catalyst but both have been investigated. The catalyst in full strength produces a slight suppression of the action potential, but this effect is transient. Silicone rubber invests the nerve, but when tested experimentally, the nerve can be easily withdrawn from the material, thus eliminating the possibility of local fiber constriction. Although silicone rubber is impermeable to water, it is less so to smaller molecules such as water vapor. This possibility plus the reaction of minute amounts of the catalyst reacting with platinum, are being investigated. At present, other types of electrical contacts, surface and imbedded, are being used which are activated by many types of implanted and external power sources. It is our hope that we may find an adequate explanation for the apparent relief from pain in the trigeminal system and extend the use of this method to the central nervous system. DISCUSSION JOHN D. FRENCH (LosAngeles,Calif.) : The authors have shown that pain can be influenced by stimuli applied directly to the nervous system by artificial means. Their study, therefore, deserves the attention of the medical profession at large on two important American Journal of Surgery
Electrical Control of Facial Pain counts: as a technical development potentially of wide utility and as a physiologic study promising to add substantially to our understanding of pain. The authors have provided us with a device capable of operating effectively for a period of three years in relieving intractable pain. They have suggested that the depolarizing current they apply may be blocking painful stimuli as these are transported through the nerves themselves, and they may be right. It is also possible, however, for an analgesic effect to be induced centrally by artificial excitation applied to peripheral nerves, a phenomenon which may or may not be implicated in the observations made by the authors. Melzak and Wall have provided physiologic data which indicate that normal excitatory activity transmitted in nerves activates a mechanism which excludes pain from the central nervous system literally by closing a gate upon it within the spinal cord, and that this gate mechanism breaks down when tissue damage intensifies the painful inputs or when nerve injury prevents normal stimuli from closing the gate. It seems that this work is likely to have far reaching impact upon medicine in the future. FREDERICKL. REICHERT(San Francisco, Calif.): This is not a good paper because it is not finished. Pain is not all from the peripheral nerves, it is from the sympathetic nerves as well. Most pain is of sympathetic origin and the authors have not to my knowledge treated the sympathetic fibers. Everybody works on the trigeminal because it is a large nerve. But how should the patient be treated? Cutting that nerve does not do a bit of good in the long run. Much work remains to be done. The instrument the authors used appears adequate, but only three patients were treated, two of whom did not require nerve stimulation at all. J. ENCLEBERTDUNPHY (San Francisco, Calif.): I would like to know whether the two patients in whom the area was not activated had any sensation or transient numbness to indicate that some physiologic process might be going on or whether this was purely psychotherapy. EDMUNDJ. MORRISSEY (San Francisco, Calif.): It is difficult to discuss a procedure with which you are unfamiliar. However, this is a novel procedure and may have merit. Certainly the authors have contributed a great deal to the knowledge and treatment of tic douloureux. They were the first to bring to our attention the permanent relief obtained in a high percentage of these patients by rubbing rather than sectioning the posterior root, which does not result in loss of sensation, whereas sectioning does. In a few instances loss of sensation is complained of almost as much as the original pain. Occasionally a patient will have bilateral pain, and sectioning both roots is not warranted because of the Vol.
114. August 1967
211
disabling features. In these cases, rubbing the posterior root is of inestimable value. In patients with unilateral tic duoloureux I still section the posterior root either partially or completely, depending on which divisions are involved. If these patients are to be subjected to surgery, it is best to assure them that there will be no recurrence of pain. It has been truly stated that if a patient is not willing to sacrifice pain for anesthesia, he does not have tic douloureux. BERTRAM FEINSTEIN (San Francisco, Calif.) : This paper is in keeping with Drs. Shelden and Pudenz delightfully creative work. The question of pain, of course, has intrigued us all, not only in neurosurgery but in all fields of medicine as well. Some time ago Drs. Thompson and Inman at the University of California successfully used high frequency stimulation of peripheral nerves to map out the various dermatomes. Years ago, Mitchell pointed out that phantom pain in the causalgic state could be relieved by pounding the stumps. Later on Russell refined the procedure by using a vibrator. Electrodes have been left in the thalamus in man for quite long periods. I wonder if the central mechanism to which Dr. French alluded is not indeed coming into play here. Dr. Jamieson and I and others at the University of California injected hypertonic saline into the interspinous segments in a number of cases. Referred pain as well as numbness in those areas was demonstrated. In other words, if we were injecting lower down, we would get a distribution not only of referred pain but also, by testing, of hypasthenia and almost anesthesia in areas completely removed. JOHNE. RAAF (Portland, Ore.) : Alcohol injection of the peripheral branches of the fifth cranial nerve is still good treatment for tic douloureux. Ten years ago I reviewed my series of 500 patients with trifacial neuralgia and found that injection of the second division resulted in about two and a half years’ relief on the average. Injection of the third division resulted in about two years relief. Only in those patients who cannot be relieved by alcohol injection of the various branches of the fifth nerve have I resorted to surgery. Patients with trifacial neuralgia have an extremely variable course. Sometimes the pain will stop spontaneously for many months or even years. Some of the patients that I have injected with alcohol have had fifteen or even twenty years’ relief. Some have never had recurrence of pain after one injection. Therefore, I think that in drawing conclusions about the treatment of trifacial neuralgia, one must have a large series extending over a long period of time. Drs. Shelden and Pudenz have been in the forefront in the treatment of trifacial neuralgia and certainly are to be congratulated on this approach.
C. IILJNTER SHELDEN (closing): LVe employed a small implanted receiver in a patient with left facial hemispasm. Her facial twitching was almost continuous and distressing since, as a librarian, she had to meet the public continually. We inserted wire electrodes into the facial nerve distal to the styloid foramen. The radio-receiving unit was implanted in the occipital bone and she has had no motor tic in the face for two years. During this time the residual facial weakness from three previous operative procedures showed improvement. With imagination, one can conceive myriad types of electromagnetic waves continually passing through our body. Their frequencies may vary greatly. We also have innumerable fundamental particles such as neutrinos passing through us. These unknown factors may later prove to be of some clinical significance. The question of C fibers or small sympathetic fibers was raised by Dr. Feinstein. We are attempt-
ing to investigate the function and behavior of various sized fibers using solenoids of varying sizes and amounts of power from other sources. It is still too early to make any significant comment in this respect. With respect to skin, there appears to be some type of reverberating circuit between the brain stem and skin. It has been shown that stimulation of one branch of the trigeminal nerve can be picked up in a trigeminal root other than the one stimulated as well as in the greater occipital and greater auricular nerve. It is of interest to me that injection of the greater auricular will often temporarily eliminate trigeminal pain in the third division and injection of the greater occipital nerve frequently eliminates second division pain. There are many unknown factors in this syndrome and it may be that a portion of the problem is central in the brain stem and may be related to the axial flow within the nerve fibers.
American
Journal
of Surwy
Control
of Facial
ROBERT
From the Repartment of Neurological Surgery, of Medical Research, Huntington Memorial Pasadena, California.
because of its selective permeability, maintains an internal resting state of - 70 mv. Any adequate stimulus, mechanical or electrical, acts first to lower the resting potential to an arbitrary level, possibly -45 mv., at which point for some unknown reason the membrane permeability to sodium ions suddenly increases and positive sodium ions pour through the membrane. Thus, once the restraining influence in the membane is reduced, these positive ions stream passively down their electrical and chemical gradient and lower the internal negative potential, not only to zero but even overshooting it, producing a momentary positive potential within the nerve fiber. This produces depolarization, in which state the nerve fiber is refractory. A second impulse cannot pass this point until ionic recovery has occurred and the previous resting potential of -70 mv. is again attained. It is at this point in the passage of a nerve impulse that we have focused our interest in the hope of reproducing such a refractory state intermittently or permanently in a portion of the fiber population of a nerve or its central projection. By so doing, we might prevent the normal process of recovery which is largely the result of extrusion of the sodium ions from the interior of the fiber by an active transport mechanism termed the sodium pump. We are conducting an in-depth study of electric and electromagnetic methods of altering or interrupting nervous function, but here we shall report only on our clinical results in patients with trigeminal neuralgia. The ultimate in the treatment of such a major neuralgia would be complete pain relief without associated sensory loss in the face. Such a result is theoretically possible, using the compression
Institute Hospital,
symptom which everyone understands but no one can accurately describe. It is likely that the subjective response to a given painful stimulus varies far more than the actual electrochemical impulses. This, no doubt, can be explained on the basis of the extremely complicated integration that occurs within the central nervous system. Our recent efforts have been directed toward electrical control of the recurrent paroxysmal pain in the face which constitutes the clinical syndrome described as trigeminal neuralgia. Implanted electrodes placed in the substance of the mandibular division of the trigeminal nerve appear to have been successful in controlling pain in three selected patients. The rationale of the method depends upon utilizing the refractory period in the nerve to prevent the passage of subsequent impulses. The passage of a nerve impulse is a complicated, not yet fully understood process which can be briefly summarized. A nerve fiber consists of axoplasm surrounded by a cylindric axon membrane which serves to separate the ions in the interstitial fluid from those within the nerve. The axoplasm has a negative resting potential (- 70 mv.) due chiefly to the presence of large negative organic ions, whereas outside the membrane there is a high concentration of positive sodium ions. In addition, there is a much higher concentration of potassium ions within the axoplasm. The net result of these plus other less significant ions is the creation of a chemical and electrical gradient across the membrane. The electrical gradient, however,
P
Pain*
AIN is a truly fascinating
* Presented at the Thirty-Eighth Annual Meeting of the Pacific Coast Surgical Association, Monterey, California, February 19-22, 1967. Vol.
114.
Aueust
1967
209
210
Shelden, Pudenz, and Doyle
operation which we developed in 1953 ; however, in practice it is
lator operating at 14 kc., housed in a standard flashlight case. The transmitter replaces the light and reflector assembly. The unit, when energized, draws approximately 150 milliwatts of power. The implant unit, measuring 11/4 by “/8 inches, is encased in methyl methacrylate to protect the unit, allow sterilization, and facilitate attachment to the bony margins of the temporal craniotomy. It is an inductor receiver which consists of a 14 kc. resonate circuit which, when energized at a distance of “Is inch from the transmitter, is capable of providing a potential of 10 volts. We have employed this method with three patients with third division pain who have remained pain-free and without subjective or objective sensory loss since operation. The observation period has been four, three and a half, and three and a quarter years, respectively. Originally, our major concern was whether the method would function according to design. It seems apparent that the initial goal was achieved but, as time passes, we become less certain as to the specific factors responsible for the pain relief. In fact, the many unanswered questions have been responsible for our present research program. After implantation of the unit in the first patient, numerous studies were performed, including frequent activation of the electrodes, using the external power source. We had no idea how often the nerve should be actively depolarized ; hence, a daily schedule of activation was
carried out for several weeks despite the fact that the patient was experiencing no pain. Each time the power source was applied, numbness developed in the mandibular division lasting several minutes after the power was discontinued. After the first few weeks this procedure was discontinued. The second and third patients have never had the nerve actively depolarized, yet have remained equally asymptomatic. Naturally, from our experience with the compression operation we have considered that, possibly, we are merely traumatizing the third division fibers. This is unlikely since in 1951 we treated ten patients by decompression of the nerve at the foramen ovale using a dental burr, and within a period of one year the majority of the patients had had a return of pain; within two years, all had return of pain. Our other concerns are less easily decided. Is the receiving unit in some way being activated or is there actually a current flowing between two dissimilar electrodes? Both seem unlikely. Is the platinum acting as a catalyst in a local ionic reaction, producing a minute local current? The electrodes attached to the nerve were enclosed in silicone rubber which does have a catalyst but both have been investigated. The catalyst in full strength produces a slight suppression of the action potential, but this effect is transient. Silicone rubber invests the nerve, but when tested experimentally, the nerve can be easily withdrawn from the material, thus eliminating the possibility of local fiber constriction. Although silicone rubber is impermeable to water, it is less so to smaller molecules such as water vapor. This possibility plus the reaction of minute amounts of the catalyst reacting with platinum, are being investigated. At present, other types of electrical contacts, surface and imbedded, are being used which are activated by many types of implanted and external power sources. It is our hope that we may find an adequate explanation for the apparent relief from pain in the trigeminal system and extend the use of this method to the central nervous system. DISCUSSION JOHN D. FRENCH (LosAngeles,Calif.) : The authors have shown that pain can be influenced by stimuli applied directly to the nervous system by artificial means. Their study, therefore, deserves the attention of the medical profession at large on two important American Journal of Surgery
Electrical Control of Facial Pain counts: as a technical development potentially of wide utility and as a physiologic study promising to add substantially to our understanding of pain. The authors have provided us with a device capable of operating effectively for a period of three years in relieving intractable pain. They have suggested that the depolarizing current they apply may be blocking painful stimuli as these are transported through the nerves themselves, and they may be right. It is also possible, however, for an analgesic effect to be induced centrally by artificial excitation applied to peripheral nerves, a phenomenon which may or may not be implicated in the observations made by the authors. Melzak and Wall have provided physiologic data which indicate that normal excitatory activity transmitted in nerves activates a mechanism which excludes pain from the central nervous system literally by closing a gate upon it within the spinal cord, and that this gate mechanism breaks down when tissue damage intensifies the painful inputs or when nerve injury prevents normal stimuli from closing the gate. It seems that this work is likely to have far reaching impact upon medicine in the future. FREDERICKL. REICHERT(San Francisco, Calif.): This is not a good paper because it is not finished. Pain is not all from the peripheral nerves, it is from the sympathetic nerves as well. Most pain is of sympathetic origin and the authors have not to my knowledge treated the sympathetic fibers. Everybody works on the trigeminal because it is a large nerve. But how should the patient be treated? Cutting that nerve does not do a bit of good in the long run. Much work remains to be done. The instrument the authors used appears adequate, but only three patients were treated, two of whom did not require nerve stimulation at all. J. ENCLEBERTDUNPHY (San Francisco, Calif.): I would like to know whether the two patients in whom the area was not activated had any sensation or transient numbness to indicate that some physiologic process might be going on or whether this was purely psychotherapy. EDMUNDJ. MORRISSEY (San Francisco, Calif.): It is difficult to discuss a procedure with which you are unfamiliar. However, this is a novel procedure and may have merit. Certainly the authors have contributed a great deal to the knowledge and treatment of tic douloureux. They were the first to bring to our attention the permanent relief obtained in a high percentage of these patients by rubbing rather than sectioning the posterior root, which does not result in loss of sensation, whereas sectioning does. In a few instances loss of sensation is complained of almost as much as the original pain. Occasionally a patient will have bilateral pain, and sectioning both roots is not warranted because of the Vol.
114. August 1967
211
disabling features. In these cases, rubbing the posterior root is of inestimable value. In patients with unilateral tic duoloureux I still section the posterior root either partially or completely, depending on which divisions are involved. If these patients are to be subjected to surgery, it is best to assure them that there will be no recurrence of pain. It has been truly stated that if a patient is not willing to sacrifice pain for anesthesia, he does not have tic douloureux. BERTRAM FEINSTEIN (San Francisco, Calif.) : This paper is in keeping with Drs. Shelden and Pudenz delightfully creative work. The question of pain, of course, has intrigued us all, not only in neurosurgery but in all fields of medicine as well. Some time ago Drs. Thompson and Inman at the University of California successfully used high frequency stimulation of peripheral nerves to map out the various dermatomes. Years ago, Mitchell pointed out that phantom pain in the causalgic state could be relieved by pounding the stumps. Later on Russell refined the procedure by using a vibrator. Electrodes have been left in the thalamus in man for quite long periods. I wonder if the central mechanism to which Dr. French alluded is not indeed coming into play here. Dr. Jamieson and I and others at the University of California injected hypertonic saline into the interspinous segments in a number of cases. Referred pain as well as numbness in those areas was demonstrated. In other words, if we were injecting lower down, we would get a distribution not only of referred pain but also, by testing, of hypasthenia and almost anesthesia in areas completely removed. JOHNE. RAAF (Portland, Ore.) : Alcohol injection of the peripheral branches of the fifth cranial nerve is still good treatment for tic douloureux. Ten years ago I reviewed my series of 500 patients with trifacial neuralgia and found that injection of the second division resulted in about two and a half years’ relief on the average. Injection of the third division resulted in about two years relief. Only in those patients who cannot be relieved by alcohol injection of the various branches of the fifth nerve have I resorted to surgery. Patients with trifacial neuralgia have an extremely variable course. Sometimes the pain will stop spontaneously for many months or even years. Some of the patients that I have injected with alcohol have had fifteen or even twenty years’ relief. Some have never had recurrence of pain after one injection. Therefore, I think that in drawing conclusions about the treatment of trifacial neuralgia, one must have a large series extending over a long period of time. Drs. Shelden and Pudenz have been in the forefront in the treatment of trifacial neuralgia and certainly are to be congratulated on this approach.
C. IILJNTER SHELDEN (closing): LVe employed a small implanted receiver in a patient with left facial hemispasm. Her facial twitching was almost continuous and distressing since, as a librarian, she had to meet the public continually. We inserted wire electrodes into the facial nerve distal to the styloid foramen. The radio-receiving unit was implanted in the occipital bone and she has had no motor tic in the face for two years. During this time the residual facial weakness from three previous operative procedures showed improvement. With imagination, one can conceive myriad types of electromagnetic waves continually passing through our body. Their frequencies may vary greatly. We also have innumerable fundamental particles such as neutrinos passing through us. These unknown factors may later prove to be of some clinical significance. The question of C fibers or small sympathetic fibers was raised by Dr. Feinstein. We are attempt-
ing to investigate the function and behavior of various sized fibers using solenoids of varying sizes and amounts of power from other sources. It is still too early to make any significant comment in this respect. With respect to skin, there appears to be some type of reverberating circuit between the brain stem and skin. It has been shown that stimulation of one branch of the trigeminal nerve can be picked up in a trigeminal root other than the one stimulated as well as in the greater occipital and greater auricular nerve. It is of interest to me that injection of the greater auricular will often temporarily eliminate trigeminal pain in the third division and injection of the greater occipital nerve frequently eliminates second division pain. There are many unknown factors in this syndrome and it may be that a portion of the problem is central in the brain stem and may be related to the axial flow within the nerve fibers.
American
Journal
of Surwy