In1 J. Radiorm
Oncology Bid.
Phps.. 1976,. Vol.
1. pp. 51 I-514.
Perpamon Press
Printed m the U.S.A.
PAIN AND ITS RELIEF ROBERT S. BOURKE, M.D. Division of Neurosurgery, Albany Medical College, Albany, NY 12208, U.S.A. Reiief of pain, Pharmacologic management, Surgical management, The physician who attends patients with malignant disease must draw a practical distinction between the management of pain as a symptom requiring analysis and treatment of underlying causes and pain as suffering requiring considerate treatment of the symptom per se. Unremitting pain associated with cancer is a late manifestation. A sympathetic physician whose analytical powers are burdened by feelings of hopelessness and helplessness in the face of a patient’s advancing malignancy may pursue symptomatic pain relief through prescription of narcotic agents without maintainance of adjuvant clinical reflection. The outcome can be most devestating to the patient. Symptomatic treatment of constant midline back pain in a patient known to have metastatic cancer without detailed investigation of the clinical syndrome may obscure the reality of malignancy-related early spinal cord compression. The development of new complaints such as difficulty in urination and obstipation which readily might raise the possibility of spinal cord compression under other diagnostic circumstances may be attributed to the side effects of the prescribed narcotic drugs. Insight into the underlying pathophysiological process may come too late to prevent paraplegia. Other similar examples will undoubtedly come to mind readily. The first precept in the management of pain associated with malignancy must be the maintainance of analytical clinical initiatives. INTRACTABLE
electrodes.
at altering the course of the process requires symptomatic treatment which alters the patient’s perception of or reaction to pain. Pain at this stage of the disease is usually constant with exacerbations. Often. we physicians institute the use of analgesic drugs to treat the exacerbations but not the pervasive background of pain. Hence, analgesic medication is ordered to be taken p.r.n. Following this dosage plan, resultant analgesia is partial at best. The practical aim of symptomatic treatment is the provision of total pain relief with preservation of physical, intellectual and emotional strengths. Therefore, the prescription of analgesic drugs ought to be directed toward this end. Scheduled, rather than episodic use of analgesic agents will be effective in this regard. Saunders” has pointed out that “pain itself is the strongest antagonist to successful analgesia and if it is ever allowed to become severe the patient will then increase it with his own tension and fear”. The secret in the use of medication for the management of intractable pain lies as much in proper dosage scheduling as in drug selection. Initially. one employs non narcotic analgesic drugs for pain relief to avoid the untoward side effects of narcotic agents. Of the spate of non narcotic analgesic drugs available for the treatment of pain in malignancy, aspirin has been shown to be most effective. A randomized, double-blind study carried out by Moertel and associates’ compared 9 drugs and a placebo for effectiveness in pain relief in 57 patients suffering pain from unresectable cancer. The drugs and respective dosages compared in this study were as follows: Aspirin, 650 mg; Pentazocine (Talwin). SOmg: acetaminophen, 650 mg: Phenacetin. 650 mg; Mefenamic acid (Pontreatment malignant
PAIN: PHARMACOLOGIC MANAGEMENT
Pain associated sion of brachial or nerves, parietal periosteum which
Implanted
with carcinomatous invalumbar plexus, intercostal pleura, peritoneum and persists despite specific 511
directed
512
Radiation Oncology 0 Biology 0 Physics
stel), 250 mg; Codeine. 65 mg; Propoxyphene (Darvon), 65 mg; Ethoheptazine, (Zacterin), 75 mg; Promazine, 25 mg; and Placebo. The paucity of side effects and relatively low cost coupled with high clinical efficacy in achieving pain relief recommend aspirin as an analgesic agent in the management of pain associated with malignancy. For those patients who can not tolerate aspirin, the para-aminophenol derivatives, acetaminophen and phenacetin were also shown to be effective analgesics. At times a patient will enjoy pain relief using non narcotic analgesics during waking hours only to find that pain becomes an intolerable thief of sleep during evening hours. Sometimes the addition of phenothiazines, sedatives or hypnotic agents may be of use; at other times, the nocturnal use of narcotic agents is effective in providing pain relief. The nocturnal use of narcotic drugs in this regard does not indicate that the patient will require them in place of non narcotic analgesics during daytime waking hours. Every attempt should be made to provide the patient with pain free sleep. Chronic fatigue is also a major antagonist of successful analgesia. The increasing intensity of pain associated with cancer frequently leads to the use of narcotic agents. Detailed understanding of drug dose-effectiveness and drug related complications are necessary for the proper clinical use of narcotic drugs. Generally, increasing the frequency of administration of narcotic agents rather than increasing the dose is found to be more effective in obtaining pain relief as the severity of unremitting pain increases. We have found that a modification of the Brompton mixture may be very effective in the management of chronic severe intractable pain. As employed each 15 ml for oral use contains the following: morphine sulfate, 15 mg; cocaine, 10 mg; alcohol (95%), 2 ml; flavored syrup, 4 ml; chloroform water (0.25% solution) to make up to 15 ml. The amount of the mixture required to gain freedom from chronic pain is determined individually. The understanding physician comprehends that the treatment of unremitting pain in the cancer patient is, in large measure, the appreciation and management of the duress to which the patient is subject. Pain-begotten
March-April
1976, Vol. 1. Number 5 and Number 6
emotional distress, feelings of aloneness, inner rage at one’s own dependence on one’s failing physiology all conspire against successful analgesia whatever the clinical regimen employed. Pain-occassioried mental anguish may, indeed, be the most intractable pain of all;’ those who manage intractable pain in malignancy most effectively are usually those who most ably combine the physician’s art with science. INTRACTABLE PAIN: SURGICAL MANAGEMENT Surgical relief of intractable pain associated with malignant disease is accomplished by alteration of the perception of or interpretation of pain when treatment is solely directed towards symptomatic relief. In general, procedures directed at the peripheral or central nervous system structures to the level of the thalamus affect the perception of pain while procedures directed at thalamic and suprathalamic structures affect the interpretation of pain and associated suffering. The site chosen for surgical intervention depends on the distribution and anatomical cause of pain. For example, pain in the distribution of intercostal nerves associated with pathologic fracture of cancer-burdened ribs may be controlled by simple intercostal nerve block if the site of fracture is distal to the site of block. Discrete pain in the distribution of intercostal nerves occasioned by carcinomatous invasion of the paravertebral chest wall may require surgical section of the posterior sensory roots adjacent to the spinal cord when adequate nerve block is not technically possible. A major advance in the surgical control of pain followed the understanding that pain and temperature conducting (spinothalamic) tracts were carried in the anterolateral quadrants of the spinal cord.’ As recently as 1912,8 it was shown to be possible to interrupt pain and temperature conducting tracts (spinothalamic tractotomy) with preservation of the senses of touch and position as well as motor function. Spinothaiamic tractotomy is most effective when the sufferer, who may have only a modest life expectancy, is not dependent on narcotic drugs. However, a patient who otherwise is a candidate for spinothalamic
Pain and its relief 0 R. S. BOURKE
tractotomy ought not be denied surgery because of narcotic drug dependence. Often gratifying pain relief and successful narcotic withdrawal is followed by post operative use of methadone in regular, though decreasing doses over a period of several weeks. In general, spinothalamic tractotomy can be expected to provide effective pain relief in malignant disease in 70430%’ of cases. Causes of less than optimal pain relief include late failures following fall in the spinal level of analgesia. Occasionally new, pain causing, malignant lesions beyond the anatomical confines of the analgesic area appear. Also. pain which was interpreted initially as being unilateral by the patient is found, after successful surgical relief, to have masked contralateral and previously unappreciated pain. The mortality associated with spinothalamic tractomy in the cancer patient is lO-20%’ These figures obscure the fact that the mortality directly related to the operative procedure itself is very small. Post surgical, in-hospital deaths occur mainly from intercurrent disorders. Complications associated with spinothalamic tractotomy include urinary retention, hypotension, ventillatory depression contralateral extremity weakness and altered sexual function. Urinary retention to some degree occurs in 10-20%9 of patients. It is more likely to occur after bilateral procedures, and particularly when the carcinomatous process involves pelvic structures. Similarly, hypotention and ventillatory depression are likely to occur after bilateral procedures; the latter occurs after procedures performed at spinal cord sites above the phrenic outflow. Percutaneous, stereotactic procedures under local anaesthesia have been developed: these circumvent the necessity for performing a major surgical procedure in a debilitated patient.’ Surgical relief of pain associated with head
513
and neck cancer is usually sought after extensive surgical and radiotherapeutic treatment has been provided. Frequently intractable pain may signify altered tempromandibular joint function, obstruction of a paranasal sinus, or radiotherapy-related alteration in dentition; correction of the local disorder rather than a pain relieving procedure is indicated. Both the character of the pain and suffering are important considerations in the choice of pain relieving procedures. These procedures include chemical neurolysis, percutaneous electrocoagulation of the branches of the trigeminus, intracranial and percutaneous medullary tractotomy, cranial nerve and high cervical sensory rhizotomy. Procedures directed primarily at the relief of suffering rather than the perception of pain include stereotactic thalamotomy, cingulumotomy and frontal leucotomy. Under all circumstances, intractable, ill defined, pain may be related closely to emotional depression. This is particularly so when pain is considered around the head and face. Furthermore, head pain may signify increased intracranial pressure from metastatic disease either involving the meninges or the brain parenchyma. NEWER TECHNIQUES FOR PAIN RELIEF ON THE HORIZON Melzack and Wall’ have proposed a spinal gating mechanism, whereby non painful impulses carrying precise tactile information into the dorsal spinal columns serve to inhibit transmission to painful stimuli. Techniques are being developed to provide tolerable competing stimuli to inhibit painful ones. Direct stimulation of the dorsal columns of spinal cord white matter, by implanted electrodes’ percutaneous and even transcutaneous peripheral nerve stimulation by small portable impulse generator;’ and modified acupuncture may prove of value in the management of pain. It is too early to evaluate comparative effectiveness of these techniques.
REFERENCES Long, D.M.: External electrical stimulation as a treatment of chronic pain. Minn. Med. 57: 195-198. 1974.
3. Melzack, R., Wall, P.D.: Pain mechanisms: A new theory. Science 150: 971-979. 1965. 3. Moertel. C.G.. Ahmann, D.L., Taylor. W.F..
514
4. 5.
6.
7.
Radiation Oncology 0 Biology ??Physics
Schwartau, B.S.: A comparative evaluation of marketed analgesic drugs. N. Engl. .I. Med. 286: 813-815, 1972. Mullan, S.: Percutaneous cordotomy for pain. Surg. Clin. N. Am. 46: 3-12, 1966. Saunders, C.: The treatment of intractable pain in terminal cancer. Proc. Roy. Sot. Med. 56: 195-197, 1%3. Shealy, C.N., Mortimer, J.T., Hagfors, N.R.: Dorsal column electroanalgesia. J. Neurosurg. 32: 560-564, 1970. Spiller, W.G.: The occasional clinical resemblance between caries of the vertebral and lumbo-thoracic syringomyelia. and the location
March-April
1976. Vol. 1, Number 5 and Number 6
within the spinal cord of the fibers for the sensations of pain and temperature. Univ. Penn. Med. Bull. 18: 147-154, 1905. 8. Spiller, W.G.,, Martin, E.: The treatment of persistent pain of organic origin in the lower part of the body by division of the anterolateral column of the spinal cord. J.A.M.A. 58: 14891490, 1914. 9. White, J.C., Sweet, J.H.: Spinothalamic tractotomy: complication, technique and review of new alternative procedure, In Pain and the Charles Thomas, Springfield, Neurosurgeon. 1%9, pp. 727-772.
Oncology Bid.
Phps.. 1976,. Vol.
1. pp. 51 I-514.
Perpamon Press
Printed m the U.S.A.
PAIN AND ITS RELIEF ROBERT S. BOURKE, M.D. Division of Neurosurgery, Albany Medical College, Albany, NY 12208, U.S.A. Reiief of pain, Pharmacologic management, Surgical management, The physician who attends patients with malignant disease must draw a practical distinction between the management of pain as a symptom requiring analysis and treatment of underlying causes and pain as suffering requiring considerate treatment of the symptom per se. Unremitting pain associated with cancer is a late manifestation. A sympathetic physician whose analytical powers are burdened by feelings of hopelessness and helplessness in the face of a patient’s advancing malignancy may pursue symptomatic pain relief through prescription of narcotic agents without maintainance of adjuvant clinical reflection. The outcome can be most devestating to the patient. Symptomatic treatment of constant midline back pain in a patient known to have metastatic cancer without detailed investigation of the clinical syndrome may obscure the reality of malignancy-related early spinal cord compression. The development of new complaints such as difficulty in urination and obstipation which readily might raise the possibility of spinal cord compression under other diagnostic circumstances may be attributed to the side effects of the prescribed narcotic drugs. Insight into the underlying pathophysiological process may come too late to prevent paraplegia. Other similar examples will undoubtedly come to mind readily. The first precept in the management of pain associated with malignancy must be the maintainance of analytical clinical initiatives. INTRACTABLE
electrodes.
at altering the course of the process requires symptomatic treatment which alters the patient’s perception of or reaction to pain. Pain at this stage of the disease is usually constant with exacerbations. Often. we physicians institute the use of analgesic drugs to treat the exacerbations but not the pervasive background of pain. Hence, analgesic medication is ordered to be taken p.r.n. Following this dosage plan, resultant analgesia is partial at best. The practical aim of symptomatic treatment is the provision of total pain relief with preservation of physical, intellectual and emotional strengths. Therefore, the prescription of analgesic drugs ought to be directed toward this end. Scheduled, rather than episodic use of analgesic agents will be effective in this regard. Saunders” has pointed out that “pain itself is the strongest antagonist to successful analgesia and if it is ever allowed to become severe the patient will then increase it with his own tension and fear”. The secret in the use of medication for the management of intractable pain lies as much in proper dosage scheduling as in drug selection. Initially. one employs non narcotic analgesic drugs for pain relief to avoid the untoward side effects of narcotic agents. Of the spate of non narcotic analgesic drugs available for the treatment of pain in malignancy, aspirin has been shown to be most effective. A randomized, double-blind study carried out by Moertel and associates’ compared 9 drugs and a placebo for effectiveness in pain relief in 57 patients suffering pain from unresectable cancer. The drugs and respective dosages compared in this study were as follows: Aspirin, 650 mg; Pentazocine (Talwin). SOmg: acetaminophen, 650 mg: Phenacetin. 650 mg; Mefenamic acid (Pontreatment malignant
PAIN: PHARMACOLOGIC MANAGEMENT
Pain associated sion of brachial or nerves, parietal periosteum which
Implanted
with carcinomatous invalumbar plexus, intercostal pleura, peritoneum and persists despite specific 511
directed
512
Radiation Oncology 0 Biology 0 Physics
stel), 250 mg; Codeine. 65 mg; Propoxyphene (Darvon), 65 mg; Ethoheptazine, (Zacterin), 75 mg; Promazine, 25 mg; and Placebo. The paucity of side effects and relatively low cost coupled with high clinical efficacy in achieving pain relief recommend aspirin as an analgesic agent in the management of pain associated with malignancy. For those patients who can not tolerate aspirin, the para-aminophenol derivatives, acetaminophen and phenacetin were also shown to be effective analgesics. At times a patient will enjoy pain relief using non narcotic analgesics during waking hours only to find that pain becomes an intolerable thief of sleep during evening hours. Sometimes the addition of phenothiazines, sedatives or hypnotic agents may be of use; at other times, the nocturnal use of narcotic agents is effective in providing pain relief. The nocturnal use of narcotic drugs in this regard does not indicate that the patient will require them in place of non narcotic analgesics during daytime waking hours. Every attempt should be made to provide the patient with pain free sleep. Chronic fatigue is also a major antagonist of successful analgesia. The increasing intensity of pain associated with cancer frequently leads to the use of narcotic agents. Detailed understanding of drug dose-effectiveness and drug related complications are necessary for the proper clinical use of narcotic drugs. Generally, increasing the frequency of administration of narcotic agents rather than increasing the dose is found to be more effective in obtaining pain relief as the severity of unremitting pain increases. We have found that a modification of the Brompton mixture may be very effective in the management of chronic severe intractable pain. As employed each 15 ml for oral use contains the following: morphine sulfate, 15 mg; cocaine, 10 mg; alcohol (95%), 2 ml; flavored syrup, 4 ml; chloroform water (0.25% solution) to make up to 15 ml. The amount of the mixture required to gain freedom from chronic pain is determined individually. The understanding physician comprehends that the treatment of unremitting pain in the cancer patient is, in large measure, the appreciation and management of the duress to which the patient is subject. Pain-begotten
March-April
1976, Vol. 1. Number 5 and Number 6
emotional distress, feelings of aloneness, inner rage at one’s own dependence on one’s failing physiology all conspire against successful analgesia whatever the clinical regimen employed. Pain-occassioried mental anguish may, indeed, be the most intractable pain of all;’ those who manage intractable pain in malignancy most effectively are usually those who most ably combine the physician’s art with science. INTRACTABLE PAIN: SURGICAL MANAGEMENT Surgical relief of intractable pain associated with malignant disease is accomplished by alteration of the perception of or interpretation of pain when treatment is solely directed towards symptomatic relief. In general, procedures directed at the peripheral or central nervous system structures to the level of the thalamus affect the perception of pain while procedures directed at thalamic and suprathalamic structures affect the interpretation of pain and associated suffering. The site chosen for surgical intervention depends on the distribution and anatomical cause of pain. For example, pain in the distribution of intercostal nerves associated with pathologic fracture of cancer-burdened ribs may be controlled by simple intercostal nerve block if the site of fracture is distal to the site of block. Discrete pain in the distribution of intercostal nerves occasioned by carcinomatous invasion of the paravertebral chest wall may require surgical section of the posterior sensory roots adjacent to the spinal cord when adequate nerve block is not technically possible. A major advance in the surgical control of pain followed the understanding that pain and temperature conducting (spinothalamic) tracts were carried in the anterolateral quadrants of the spinal cord.’ As recently as 1912,8 it was shown to be possible to interrupt pain and temperature conducting tracts (spinothalamic tractotomy) with preservation of the senses of touch and position as well as motor function. Spinothaiamic tractotomy is most effective when the sufferer, who may have only a modest life expectancy, is not dependent on narcotic drugs. However, a patient who otherwise is a candidate for spinothalamic
Pain and its relief 0 R. S. BOURKE
tractotomy ought not be denied surgery because of narcotic drug dependence. Often gratifying pain relief and successful narcotic withdrawal is followed by post operative use of methadone in regular, though decreasing doses over a period of several weeks. In general, spinothalamic tractotomy can be expected to provide effective pain relief in malignant disease in 70430%’ of cases. Causes of less than optimal pain relief include late failures following fall in the spinal level of analgesia. Occasionally new, pain causing, malignant lesions beyond the anatomical confines of the analgesic area appear. Also. pain which was interpreted initially as being unilateral by the patient is found, after successful surgical relief, to have masked contralateral and previously unappreciated pain. The mortality associated with spinothalamic tractomy in the cancer patient is lO-20%’ These figures obscure the fact that the mortality directly related to the operative procedure itself is very small. Post surgical, in-hospital deaths occur mainly from intercurrent disorders. Complications associated with spinothalamic tractotomy include urinary retention, hypotension, ventillatory depression contralateral extremity weakness and altered sexual function. Urinary retention to some degree occurs in 10-20%9 of patients. It is more likely to occur after bilateral procedures, and particularly when the carcinomatous process involves pelvic structures. Similarly, hypotention and ventillatory depression are likely to occur after bilateral procedures; the latter occurs after procedures performed at spinal cord sites above the phrenic outflow. Percutaneous, stereotactic procedures under local anaesthesia have been developed: these circumvent the necessity for performing a major surgical procedure in a debilitated patient.’ Surgical relief of pain associated with head
513
and neck cancer is usually sought after extensive surgical and radiotherapeutic treatment has been provided. Frequently intractable pain may signify altered tempromandibular joint function, obstruction of a paranasal sinus, or radiotherapy-related alteration in dentition; correction of the local disorder rather than a pain relieving procedure is indicated. Both the character of the pain and suffering are important considerations in the choice of pain relieving procedures. These procedures include chemical neurolysis, percutaneous electrocoagulation of the branches of the trigeminus, intracranial and percutaneous medullary tractotomy, cranial nerve and high cervical sensory rhizotomy. Procedures directed primarily at the relief of suffering rather than the perception of pain include stereotactic thalamotomy, cingulumotomy and frontal leucotomy. Under all circumstances, intractable, ill defined, pain may be related closely to emotional depression. This is particularly so when pain is considered around the head and face. Furthermore, head pain may signify increased intracranial pressure from metastatic disease either involving the meninges or the brain parenchyma. NEWER TECHNIQUES FOR PAIN RELIEF ON THE HORIZON Melzack and Wall’ have proposed a spinal gating mechanism, whereby non painful impulses carrying precise tactile information into the dorsal spinal columns serve to inhibit transmission to painful stimuli. Techniques are being developed to provide tolerable competing stimuli to inhibit painful ones. Direct stimulation of the dorsal columns of spinal cord white matter, by implanted electrodes’ percutaneous and even transcutaneous peripheral nerve stimulation by small portable impulse generator;’ and modified acupuncture may prove of value in the management of pain. It is too early to evaluate comparative effectiveness of these techniques.
REFERENCES Long, D.M.: External electrical stimulation as a treatment of chronic pain. Minn. Med. 57: 195-198. 1974.
3. Melzack, R., Wall, P.D.: Pain mechanisms: A new theory. Science 150: 971-979. 1965. 3. Moertel. C.G.. Ahmann, D.L., Taylor. W.F..
514
4. 5.
6.
7.
Radiation Oncology 0 Biology ??Physics
Schwartau, B.S.: A comparative evaluation of marketed analgesic drugs. N. Engl. .I. Med. 286: 813-815, 1972. Mullan, S.: Percutaneous cordotomy for pain. Surg. Clin. N. Am. 46: 3-12, 1966. Saunders, C.: The treatment of intractable pain in terminal cancer. Proc. Roy. Sot. Med. 56: 195-197, 1%3. Shealy, C.N., Mortimer, J.T., Hagfors, N.R.: Dorsal column electroanalgesia. J. Neurosurg. 32: 560-564, 1970. Spiller, W.G.: The occasional clinical resemblance between caries of the vertebral and lumbo-thoracic syringomyelia. and the location
March-April
1976. Vol. 1, Number 5 and Number 6
within the spinal cord of the fibers for the sensations of pain and temperature. Univ. Penn. Med. Bull. 18: 147-154, 1905. 8. Spiller, W.G.,, Martin, E.: The treatment of persistent pain of organic origin in the lower part of the body by division of the anterolateral column of the spinal cord. J.A.M.A. 58: 14891490, 1914. 9. White, J.C., Sweet, J.H.: Spinothalamic tractotomy: complication, technique and review of new alternative procedure, In Pain and the Charles Thomas, Springfield, Neurosurgeon. 1%9, pp. 727-772.
