- Email: [email protected]
Lesions of the dorsal columns
Commentary
Lesions of the Dorsal Columns Definitely Disturbing Karen J. Berkley
B
uried in the she-poetry and interpretation of the literature of the Focus article by AI-Chaer and colleagues is an emotional and potent threepoint message, as follows: First, compassion dictates that if we have strong reasons to believe that a treatment for pain can alleviate it, we should use that treatment, regardless of our ignorance of how it works or debates about the neural mechanisms of pain. Second, a small bilateral dorsal column lesion (limited myelotomy) can alleviate visceral pain with no permanent side effects. Third, the use of such a lesion to treat chronic visceral pain conditions is therefore encouraged. How could anyone disagree with the first message on the use of known effective remedies? Clinicians follow that dictum in many realms of healthcare, and we all follow it in our own personal lives. However, as I have argued recently [1] and will argue again here, such behavior does not mean that clinical approaches to treating patients and the success of those approaches are unaffected by our conceptualizations of treatment action or pain mechanisms. As for the second and third messages, evidence so far does indeed support the idea that limited myelotomy might alleviate certain visceral pains. Thus, to deny it in those cases simply because we do not yet understand how it works would be cruel indeed. However, we must remember that dorsal column lesions destroy forever one major route by which information about many bodily conditions (innocuous and nociceptive, occurring in somatic and visceral tissues), is conveyed from the periphery into the central nervous system, thence diverging to many parts of the brain to converge with information From the Program in Neuroscience, Florida State University, Tallahassee, Florida. Reprint requests: Karen J. Berkley, PhD, Before Dec. 15, 1998: 87 Sandwich House, Sandwich Street, London WC1H 9PW, United Kingdom; after Dec. 15, 1998: Program in Neuroscience, Florida State University, Tallahassee, FL 23206-1270. ©
1998 the American Pain Society
1058-9139/0703-0003$5.00
Pain Forum 7(3): 129-134, 1998
arriving via other routes [3]. The potential wide-ranging consequences of that destruction, both immediate and long-term, need careful evaluation. As discussed below and elsewhere [1,14], these potential consequences are neither trivial nor benign. Thus, what is disturbing about this Focus article is that its well-intentioned enthusiasm might overly encourage clinicians, especially those whose conceptualization of pain mechanisms is fascicular (see Focus article's Figure 1 and below), to extend their use of the relatively "simple" surgery of limited myelotomy to patient populations for whom its potential iatrogenic consequences are insignificant.
CONSEQUENCES OF DORSAL COLUMN LESIONS Sensorimotor Functions Other Than Pain Animals As would be predicted from the analyses of dorsal column function by Gilman and Denny-Brown [8] and Wall [26], dorsal column lesions in animals such as rats, cats, and monkeys produce deficits in "behavioral tasks that require temporal processing of tactile information" [19]. These deficits result in disturbances in the precision and timing of certain complex motor tasks, producing "errors in performing complex sequences of motor activity that require precise regulation of muscular force" [5]. Although the effects appear generally more severe when the lesion destroys the fasciculus cuneatus (thereby affecting forelimb and hand functions) than when the lesion destroys the fasciculus gracilis (thereby affecting hindlimb and foot functions; ie, cervical versus thoracic lesions, respectively [8] ), thoracic lesions, even small ones at the midline, can produce considerable deficits in hindlimb sensibility and movement. For examples, compare Glendinning et al. [9] and Leonard et al. [15] for effects of cervical lesions on forelimb with Ganchrow et
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several months. Importantly, however, the authors also noted that "although (these deficits) may appear slight on routine neurological examination , they can cause severe disturbances in the activities of daily living" [20].
al. [7] and Vierck et al. [25] for effects of thoracic lesions on hindlimb sensibility and movement. Many of the deficits are temporary, but the length of time to recover varies. Some deficits in fact never recover [4,18], while other deficits actually increase with time [7]. For example, in the hindlimb of monkeys, deficits in tactile size discrimination recover in 2 to 5 months [23], deficits in spatiotactile sequence recognition thresholds recover in 4 to 7 months [25], and, finally, the inability to discriminate the direction of tactile stimulus motion fails to recover even after 9 months of testing [24]. Furthermore, as shown by a study in the rat in which a large number of components of hindlimb movement performance on platforms, ladders, and parallel bars (ie, slips, recovery from slips, manner of traverse, type of movement, tail position) were analyzed following a limited lesion of the dorsal funiculus at T12 that spared its ventral component (to avoid corticospinal fibers), the number of deficits in these movement components actually increased with time from 30 to 120 days following the lesion [7]. Most of these deficits in animals might seem relatively minor, even the ones that fail to recover or increase. However, all of the examinations of these deficits have been carried out in laboratory settings. When examined in the animal's living environment , these seemingly small deficits can have significant morbid effects on the animal's social situation. For example, following dorsal column lesions at cervical levels, monkeys show longterm changes in their natural hand movements that lead to changes in grooming patterns. These changes have big effects on the monkey's social status, the severity of which depends on the monkey's dominance position within its animal colony (effects greater for the dominant monkey [15,16] ).
Most of the cases of dorsal column damage reviewed above involved fairly large lesions, either longitudinally across many segments (commissural myelotomies) or laterally and ventrally to invade dorsolateral fibers or the dorsal horn, respectively (disease, accident, lesions for phantom limb pain). In the animal literature, it is the case that large lesions, particularly those that extend laterally or invade the dorsal horn, give rise to more significant sensorimotor consequences, including hyperpathia, than do smaller lesions [7,11,14]. It could therefore be argued that lesions carefully and skillfully limited to the midline fasciculus gracilis at a single small locus within one thoracic (or further caudal) segmental level (ie, "punctate" lesion) would be unlikely to produce sensorimotor disturbances of great consequence. This prediction might indeed be correct, but published data are available on only nine patients, reported completely in two studies [12,21]. All of these patients were severely ill with incapacitating and longstanding pelvic pain associated with invasive pelvic visceral disease and were bedridden or minimally functional. Thus, for them, any relatively "minor" sensorimotor disturbance in their hindlimbs that might have been produced by the lesions might not have been noticed and would have had little impact on their daily lives in a setting in which their pain was relieved with concominant limited increases in mobility and without further disruption to their bowel or bladder functions (see below).
Humans
Pain: Humans and Animals
Although for obvious reasons much less information is available about the effects of dorsal column lesions on sensorimotor functions in humans, reviews of the available literature [10,20,22] reveal that the kinds of deficits observed in the animal studies as summarized above can occur in humans. For example, in the summary of their review, Nathan et al. [20] state that disturbances of mechanoreception attributed to lesions of the dorsal columns include "lability of threshold, persistence of sensation, tactile and postural hallucinations and temporal and spatial disturbances. In man, lesions of the dorsal columns cause an increase in pain, tickle, warmth and cold" [20]. As in animals , these sensorimotor deficits appeared to be more significant with lesions that affected forelimb function (cervical) than with those that affected hindlimb function (thoracic or further caudal), and many, but not all, were temporary, lasting from a few weeks to
The Focus article provides an excellent review of recent and past literature on the effects on pelvic visceral pain of lesions limited to the dorsal columns at thoracic levels. The newer results in humans [12,21], showing long-term dramatic acute reductions in severe, chronic pelvic pain without effects on bladder or colon function, are convincing and consistent with much earlier findings on the effects of larger dorsal column lesions or commissural myelotomies at cervical levels for conditions such as phantom limb and other severe, chronic visceral pains [10, 12, 20, 22]. The admirable and heartwarming enthusiasm and caring attitude at the obvious potential of such surgery for relieving intractable pain is evident in the text of one of the most recent of these papers. Thus, Nautaet al. [21], reporting on the effects of a punctate lesion in the midline of the dorsal columns at T8 performed on a
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39-year-old cachexic woman with insulin-dependent diabetes and severely disabled by severe pelvic pain due to extensive pathology of her bowel, bladder, and ureter induced by radiation given for cervical cancer, state (p. 540): At examination on postoperative Day 1, there were no new neurological deficits. The patient's vibratory, light touch, and proprioceptive sensation remained unchanged with only the mild changes already noted preoperatively and attributed to her preexisting diabetic neuropathy. Pain assessment ... indicated complete pain relief. Furthermore, the authors report that by 72 days after her surgery, the patient's morphine dose had been greatly reduced, she had gained appetitite and some weight (5 Ib) and "she was able to travel out of town, attend her daughter's school functions, and perform her daily household chores." Despite the development 4 months postoperatively of multiple pelvic fistulas that the authors attribute to complications of radiation in the context of diabetes mellitus, the patient remained relatively pain free. Thus, in summary, the authors were able to state that "At the time of this writing (10 months after the punctate myelotomy procedure), she has no complaints of any pain in the lower abdomen, and she continues to believe that the myelotomy eliminated her original pain without recurrence or new dysesthesias." This testimony is reminiscent of one by Leriche in 1939 [17], who, after performing in 1928 a "section of the posterior commissure" in one female patient that was completely and enduringly successful, then decided to "turn my attention in another direction in the problem of the treatment of pain (p. 470)." This direction consisted of "operations on the sympathetic." In reporting upon the results from nine patients, here is his enthusiastic and caring description of the results in one of the patients (p. 472): "A woman of 33 years of age was sent to the clinic on account of intolerable pelvic and perineal pain, with attacks of obstruction. A year previously, she had been subjected to two applications of radium for epithelioma of the cervix. For about ten months she appeared to be cured, when the pains appeared. She had to have an iliac colostomy, as a matter of urgency. This relieved her conditions considerably, but the pains persisted, and prevented any sleep. "On September 11, 1934, I advised Jung to remove the lower part of both lumbar ganglionic chains, and to resect the presacral nerve. "The result was remarkable. The pains disappeared. It was possible to stop using morphine,
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and the patient left the clinic overjoyed at being relieved of her pain. In December she developed a recto-vaginal fistula, but she had no pain. She slept well, took her food well, and busied herself about her house. In short, she led a normal existence, with the illusion of cure. And this state of well-being continued for four full months. Then she died very quickly from uraemia." There are at least two important conclusions to be drawn from these two similar case scenarios. First, we have multiple means to alleviate a patient's suffering. Second, the pains of both of the female patients were severely disabling and life-threatening, presumably due to the continuinq barrage of their nervous systems by information conveyed to it via nerves innervating their increasingly diseased pelvic organs. In that context, significant invasive procedures seemed warranted, regardless of potential "side" effects (sensorimotor in the former, autonomic in the latter). As stated earlier, this is the "context" for most of the patients in whom limited thoracic myelotomy has been successfully used. Now let us apply the above discussions to a case history.
EPIGASTRIC PAIN: A CASE HISTORY From January of 1989 until his death in 1995 at the age of 59, MarkA. Berkley, my best friend and husband of 30 years, suffered increasingly troublesome, worrisome, and severe, unrelenting, pounding epigastric pain that affected nearly all aspects of his and our family's and our social lives. For several years early on, numerous unpleasant, inconvenient, time-consuming, expensive, and sometimes invasive diagnostic procedures ruled out the heart. disease that ran in his family but failed to provide even one clue to the many experts attending him about the likely source of his pain until an adenoma at the head of his pancreas finally announced itself with jaundice more thanfour years later in August of 1993. During my husband's precancerous 1989-1993 period, small doses of ibuprofen, deliberately combined with music, cooking, gadget inventing and construction, model building, playing squash, romping with our dog, sailing and mountain climbing with his family, and absorption in his academic and technically demanding scientific research (brain mechanisms of vision) helped considerably, particularly when low doses of oxycodone were temporarily granted and added to the mix after invasive procedures, but his pains remained severe and preoccupying. In 1993, following Whipple surgery, which removed most of his pancreas and parts of surrounding organs, his pains remained, alleviated increasingly less successfully by the combinations of therapies described above (oxycodone was now deemed permanently safe)
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until his death two years later. However, for nearly 18 months after the surgery, despite his pain and fear of death, he continued to derive deliberately greater and greater pleasure in his old pursuits, such as skiing, hiking in the mountains, fussing about inventing and constructing all manner of scientific and household items big and small, and, during a 5-month teaching assignment in London in 1994, exploring by foot out-of-the-way boating facilities, art museums , bookshops, and all manner of obscure places. An important feature of this period was that his delight in these doings enhanced considerably our family's cohesiveness and pleasure in each other's company. The question arises here as to whether, at any time during the 6-year course of my husband's illness(es), a limited or punctate thoracic myelotomy should have been considered to relieve his pains. If his doctors or I had access to the information provided in this Focus article, including its reference to laudable new research indicating that dorsal column lesions in rats reduce pain behaviors in response to esophageal and pancreatic stimuli [6,13], my guess is that we might have strongly encouraged him to undergo this seemingly simple and effective mimimalist neurosurgical procedure (as dramatically illustrated so disarmingly on the cover of the March 1997 issue of the Journal of Neurosurgery [21] ) perhaps as early as 1992, when his pains had become almost continuous and dominating . Most certainly, however, it would have been considered in October 1993 several months after his Whipple surgery, because it had become clear by then that his epigastric pain would continue unabated , even with the higher doses of morphine still miserly and humiliatingly doled out at monthly intervals by his doctors. However, given the review above, consider what might have happened had he undergone such surgery at either of those times. From the analysis I provided in my editorial [1], the animal and clinical literature appears to indicate that the less the dominance and duration of severe and increasing visceral pathology, the greater the likelihood that damage of any sort to the dorsal columns would produce at least some of the sensorimotor side effects reviewed here above, especially if the lesion is more rostral and not performed as perfectly and carefully as the one described by Nauta et al. [21], thereby "accidentally" damaging parts of the dorsal horn or more lateral fibers. Thus, the development of such side effects would have been a distinct possibility for my husband, even in October 1993, in part because all tumor had been removed and he felt quite fit except for the pounding epigastric pain. For him, sustaining what might have seemed relatively minor sensorimotor deficits in a clinical setting would have been devastating to his everyday life, in which his delights were derived mainly
from activities that required dexterity, mobility, and complex muscle coordination of his hindlimbs and feet (eg, skiing, traveling, exploring difficult-to-get-to places, hiking in mountains). Even if those side effects had been "temporary," they would have used up a considerable proportion of the 18 months of relatively good health he had left to him. Given the Sophie's choice of the possibility of diminished pain with diminished sensorimo tor function in his legs, or the possibility of aggressively using his lively interests to add to the mix of his other therapies (eg, drugs and exercise , family activities, and music) to reduce the consequences of his pain, I am certain that at that time he would have preferred the latter. On the other hand, when his condition began to deteriorate rapidly during the last 5 months of his life as the tumor burden created significantly more abdominal visceral pathophysiology and robbed him of the ability to carry out his usual motor pursuits as therapy, it seems quite clear now that then , and only then, a limited thorac ic dorsal column lesion might indeed have been the best of the choices available to give him, like it has more recently for others in his condition, the relief of freedom from pain without the price of loss of other remaining functions.
CONCLUSIONS Table 1 updates another published in Reference 1, listing a vast , hopeful, and ever-increasing array of medical (column A), somatic (column S), and situational (column C) therapies that can be applied to people in pain. Although, as indicated in the Focus article, one might question the importance in clinical practice of one's . particular conceptualization of pain mechanisms, it can in fact influence how the clinician both gathers data from patients and uses the items in this table to devise treatment strategies. The fascicular conceptualization shown in Figure 1 of the Focus article reinforces traditional clinical approaches in which information is gathered mainly about the patient's morbid condition (eg, pain), and treatment consists of the application of one or only a few of the therapies listed in the table that may "work" for that type of pain condition (eg, severe chronic visceral pain). The "ensemble" conceptualization shown in Figure 2 encourages a more active cooperation between the patient and clinician , allowing the gathering of more complete information about the patient's life so that the patient and clinician can together develop a strategy of deliberate multitherapy; for example , two from column A, three from column S, four or more from column C, with the option of changing combinations if the items chosen are not effective enough or as the patient's condition or life situation changes. Thus, fascicular clinicians would be more likely to opt for limited myeloto-
COMMENTARY/Berkley
Table 1.
A growing list of therapies for pain
Somatic Interventions
Drugs Primary analgesics
NSAID acetaminophen opioids Other analgesics
Simple
heat/cold exercise massage vibration relaxation
a-2 agonists 13 adrenergic antagonists Minimally invasive physical therapy antidepressants anticonvulsants traction antiarrhythmics manipulation calcium channel blockers ultrasound cannabinoids TENS corticosteroids acupuncture GABAs agonists local anesthetics serotonin agonists Invasive
Adjuvants
antihistamines laxatives neuroleptics phenothiazines Routes
topical oral buccal sublingual intranasal vaginal rectal transfermal intramuscular intraperitoneal intravenous epidural intrathecal intraventricular
radiation therapy dorsal column stimulation nerve blocks neurectomy local ganglion blocks sympathectomy rhizotomy DREZ lesions punctate midline myelotomy limited myelotomy commisural myelotomy cordotomy brain stimulation brain lesions
Situational Approaches Clinician
education attitude clinical setting and arrangement Self
education meditation diet art, music, poetry, performing arts sports gardening aroma therapy religion Interactive
hypnosis biofeedback support groups advocacy groups networking self-help groups Structured settings
group therapy family counseling job counseling cognitivetherapy behavioraltherapy psychotherapy multidisciplinary clinic hospice
mies to treat various chronic visceral complaints than would ensemble clinicians, who would be more likely to opt for a combination of multiple approaches that include measures less invasive than damage to the spinal cord (however minimal) until the patient's situation changes enough where the prospect and impact of potential sensorimotor consequences would be minimized. With a fascicular approach, my husband might have been persuaded to undergo a limited or punctate upper thoracic myelotomy in October of 1993 that, while alleviating his pain, could have robbed him for a significant proportion of his remaining healthy time of many of the pursuits that brought him and his family so much pleasure. With the ensemble approach he had unwittingly been forced to develop for himself, however, such surgery would not have been considered for another 16 months at which time its application indeed could have been a blessing.
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Although the Focus article contains several misinterpretations of the publications of my group, I have chosen here to concentrate on the one that concerns me the most; that is, the misconception that my editorial [1] expressed "reservations about the utility of the surgical procedure" (ie, of limited or punctate thoracic myelotomy). It should be clear from the above discussion that it is not the procedure's "utility" about which I have reservations, but rather to whom and by whom it would be applied and when. I have two concerns. First, I worry that well-meaning fascicular clinicians less careful or competent than the enthusiastic few who have already done the surgery might be tempted by its seductive simplicity to consider offering it to a wider and wider range of patients with seemingly intractable visceral pain at any level of the body. Such a situation would increase the risks of iatrogenic effects. Second, I worry that patients made vulnerable by chronic disabling pelvic visceral pain that seems intractable when dealt with by well-meaning fascicular clinicians (and such patients would more likely be female than male; [2]) might be tempted and awed by the attraction and authority of a neurosurgical quick fix at a time when they might be more vulnerable to its as yet unknown, but distinctly possible, morbid consequences on other aspects of their daily lives. Acknowledgment I thank Dr. Anita Holdcroft for her help in the preparation of Table 1 (updated from Ref. [1J).
References 1. Berkley KJ: On the dorsal columns: translating basic research hypotheses to the clinic (Editorial). Pain 70:103107,1997 2. Berkley KJ: Sex differences in pain. Behav Brain Sci 20:371-380, 1997 3. Berkley KJ, Hubscher CH: Visceral and somatosensory tracks through the .neuroaxis and their relation to pain: lessons from the rat female reproductive system. pp. 195-216, 1995. In Gebhart GF (ed): Visceral pain, Progress in pain research and management, Vol. 5, GF IASP Press, Seattle 4. Berkley KJ, Vierck CJ Jr: Reduced retrograde labeling of diencephalic-projecting neurons in the gracile nucleus of the monkey tollowinq removal of dorsal column input. Exp NeuroI123:64-73, 1993 5. Davidoff RA: The dorsal columns. Neurology 39:13771385,1989 6. Feng Y, Cui M, AI-Chaer ED, Willis WD: Epigastric antinociception by cervical dorsal column lesions in rats. (Submitted) 7. Ganchrow D, Margolin JK, Bernstein JJ: Component analysis of hind limb behavioral alterations after damage to the rat dorsal funiculus. Exp Neurol 70:339-355, 1980
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8. Gilman S, Denny-Brown 0: Disorders of movement and behaviour following dorsal column lesions. Brain 89:397418,1966
18. Makous JC, Vierck CJ Jr: Physiological changes during recovery from a primate dorsal column lesion. Somatosens Mot Res 11:183-192, 1994
9. Glendinning OS, Cooper BY, Vierck CJ Jr, Leonard CM: Altered precision grasping in stumptail macaques after fasciculus cuneatus lesions. Somatosen Mot Res 9:6163, 1991
19. Makous JC, Friedman RM, Vierck CJ Jr: Effects of a dorsal column lesion on temporal processing within the somatosensory system of primates. Exp Brain Res 112:253-267, 1996
10. Gybels JM, Sweet WH: Neurosurgical treatment of persistent pain. Physiological and pathological mechanisms of human pain. Karger, Basel, 442 pp. 1989
20. Nathan PW, Smith MC, Cook AW: Sensory effects in man of lesions of the posterior columns and of some other afferent pathways. Brain 109: 1003-1 041, 1986
11. Hai J-X, Xu X-J, Aldskogius H, Seiger A, Wiesenfeld-Hallin Z: Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation. Pain 45:175-185,1991 12. Hirshberg RM, AI-Chaer ED, Lawand NB, Westlund KN, Willis WD: Is there a pathway in the posterior funiculus that signals visceral pain? Pain 67:291-305,1996 13. Houghton AK, Kadura S, Westlund KN: Dorsal column lesions reverse the reduction of homecage activity in rats with pancreatitis. NeuroRep 8:3795-3800, 1997 14. Hubscher CH: Comments on Berkley (letter). Pain 72:293292,1997 15. Leonard CM, Glendinning OS, Wilfong T, Cooper BY, Vierck CJ Jr: Alterations of natural hand movements after interruption of fasciculus cuneatus in the Macaque. Somatosens. Mot Res 9:75-89, 1992 16. Leonard CM, Vierck CJ Jr, Cooper BY: Social grooming after a dorsal column lesion in the Macaque. Soc Neurosci Abstr 12:497, 1986 17. Leriche R: The Surgery of Pain. London, Bailhere, Tindall and Cox, 1939
21. Nauta HJW, Hewitt E, Westlund KN, Willis WD Jr: Surgical interruption of a midline dorsal column visceral pain pathway. J Neurosurg 86:538-542, 1997 22. Sweet WH, Poletti CE, Gybels JM: Operations in the brainstem and spinal canal, with an appendix on the relationship of open to percutaneous cordotomy. pp. 11131135. In Wall PO, Melzack R (eds): Textbook of pain, 3rd ed., Edinburgh, Churchill Livingstone, 1994 23. Vierck CV Jr: Alterations of spatio-tactile discrimination after lesions of primate spinal cord. Brain Res 58:69-79, 1973 24. Vierck CV Jr: Tactile movement detection and discrimination following dorsal column lesions in monkeys. Exp Brain Res 20:331-346, 1974 25. Vierck CV Jr, Cohen RH, Cooper BY: Effects of spinal tractotomy on spatial sequence recognition in macaques. J Neurosci 3:280-290, 1983 26. Wall PO: The sensory and motor role of impulses travelling in the dorsal columns towards cerebral cortex. Brain 93:505-524, 1970
Lesions of the Dorsal Columns Definitely Disturbing Karen J. Berkley
B
uried in the she-poetry and interpretation of the literature of the Focus article by AI-Chaer and colleagues is an emotional and potent threepoint message, as follows: First, compassion dictates that if we have strong reasons to believe that a treatment for pain can alleviate it, we should use that treatment, regardless of our ignorance of how it works or debates about the neural mechanisms of pain. Second, a small bilateral dorsal column lesion (limited myelotomy) can alleviate visceral pain with no permanent side effects. Third, the use of such a lesion to treat chronic visceral pain conditions is therefore encouraged. How could anyone disagree with the first message on the use of known effective remedies? Clinicians follow that dictum in many realms of healthcare, and we all follow it in our own personal lives. However, as I have argued recently [1] and will argue again here, such behavior does not mean that clinical approaches to treating patients and the success of those approaches are unaffected by our conceptualizations of treatment action or pain mechanisms. As for the second and third messages, evidence so far does indeed support the idea that limited myelotomy might alleviate certain visceral pains. Thus, to deny it in those cases simply because we do not yet understand how it works would be cruel indeed. However, we must remember that dorsal column lesions destroy forever one major route by which information about many bodily conditions (innocuous and nociceptive, occurring in somatic and visceral tissues), is conveyed from the periphery into the central nervous system, thence diverging to many parts of the brain to converge with information From the Program in Neuroscience, Florida State University, Tallahassee, Florida. Reprint requests: Karen J. Berkley, PhD, Before Dec. 15, 1998: 87 Sandwich House, Sandwich Street, London WC1H 9PW, United Kingdom; after Dec. 15, 1998: Program in Neuroscience, Florida State University, Tallahassee, FL 23206-1270. ©
1998 the American Pain Society
1058-9139/0703-0003$5.00
Pain Forum 7(3): 129-134, 1998
arriving via other routes [3]. The potential wide-ranging consequences of that destruction, both immediate and long-term, need careful evaluation. As discussed below and elsewhere [1,14], these potential consequences are neither trivial nor benign. Thus, what is disturbing about this Focus article is that its well-intentioned enthusiasm might overly encourage clinicians, especially those whose conceptualization of pain mechanisms is fascicular (see Focus article's Figure 1 and below), to extend their use of the relatively "simple" surgery of limited myelotomy to patient populations for whom its potential iatrogenic consequences are insignificant.
CONSEQUENCES OF DORSAL COLUMN LESIONS Sensorimotor Functions Other Than Pain Animals As would be predicted from the analyses of dorsal column function by Gilman and Denny-Brown [8] and Wall [26], dorsal column lesions in animals such as rats, cats, and monkeys produce deficits in "behavioral tasks that require temporal processing of tactile information" [19]. These deficits result in disturbances in the precision and timing of certain complex motor tasks, producing "errors in performing complex sequences of motor activity that require precise regulation of muscular force" [5]. Although the effects appear generally more severe when the lesion destroys the fasciculus cuneatus (thereby affecting forelimb and hand functions) than when the lesion destroys the fasciculus gracilis (thereby affecting hindlimb and foot functions; ie, cervical versus thoracic lesions, respectively [8] ), thoracic lesions, even small ones at the midline, can produce considerable deficits in hindlimb sensibility and movement. For examples, compare Glendinning et al. [9] and Leonard et al. [15] for effects of cervical lesions on forelimb with Ganchrow et
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several months. Importantly, however, the authors also noted that "although (these deficits) may appear slight on routine neurological examination , they can cause severe disturbances in the activities of daily living" [20].
al. [7] and Vierck et al. [25] for effects of thoracic lesions on hindlimb sensibility and movement. Many of the deficits are temporary, but the length of time to recover varies. Some deficits in fact never recover [4,18], while other deficits actually increase with time [7]. For example, in the hindlimb of monkeys, deficits in tactile size discrimination recover in 2 to 5 months [23], deficits in spatiotactile sequence recognition thresholds recover in 4 to 7 months [25], and, finally, the inability to discriminate the direction of tactile stimulus motion fails to recover even after 9 months of testing [24]. Furthermore, as shown by a study in the rat in which a large number of components of hindlimb movement performance on platforms, ladders, and parallel bars (ie, slips, recovery from slips, manner of traverse, type of movement, tail position) were analyzed following a limited lesion of the dorsal funiculus at T12 that spared its ventral component (to avoid corticospinal fibers), the number of deficits in these movement components actually increased with time from 30 to 120 days following the lesion [7]. Most of these deficits in animals might seem relatively minor, even the ones that fail to recover or increase. However, all of the examinations of these deficits have been carried out in laboratory settings. When examined in the animal's living environment , these seemingly small deficits can have significant morbid effects on the animal's social situation. For example, following dorsal column lesions at cervical levels, monkeys show longterm changes in their natural hand movements that lead to changes in grooming patterns. These changes have big effects on the monkey's social status, the severity of which depends on the monkey's dominance position within its animal colony (effects greater for the dominant monkey [15,16] ).
Most of the cases of dorsal column damage reviewed above involved fairly large lesions, either longitudinally across many segments (commissural myelotomies) or laterally and ventrally to invade dorsolateral fibers or the dorsal horn, respectively (disease, accident, lesions for phantom limb pain). In the animal literature, it is the case that large lesions, particularly those that extend laterally or invade the dorsal horn, give rise to more significant sensorimotor consequences, including hyperpathia, than do smaller lesions [7,11,14]. It could therefore be argued that lesions carefully and skillfully limited to the midline fasciculus gracilis at a single small locus within one thoracic (or further caudal) segmental level (ie, "punctate" lesion) would be unlikely to produce sensorimotor disturbances of great consequence. This prediction might indeed be correct, but published data are available on only nine patients, reported completely in two studies [12,21]. All of these patients were severely ill with incapacitating and longstanding pelvic pain associated with invasive pelvic visceral disease and were bedridden or minimally functional. Thus, for them, any relatively "minor" sensorimotor disturbance in their hindlimbs that might have been produced by the lesions might not have been noticed and would have had little impact on their daily lives in a setting in which their pain was relieved with concominant limited increases in mobility and without further disruption to their bowel or bladder functions (see below).
Humans
Pain: Humans and Animals
Although for obvious reasons much less information is available about the effects of dorsal column lesions on sensorimotor functions in humans, reviews of the available literature [10,20,22] reveal that the kinds of deficits observed in the animal studies as summarized above can occur in humans. For example, in the summary of their review, Nathan et al. [20] state that disturbances of mechanoreception attributed to lesions of the dorsal columns include "lability of threshold, persistence of sensation, tactile and postural hallucinations and temporal and spatial disturbances. In man, lesions of the dorsal columns cause an increase in pain, tickle, warmth and cold" [20]. As in animals , these sensorimotor deficits appeared to be more significant with lesions that affected forelimb function (cervical) than with those that affected hindlimb function (thoracic or further caudal), and many, but not all, were temporary, lasting from a few weeks to
The Focus article provides an excellent review of recent and past literature on the effects on pelvic visceral pain of lesions limited to the dorsal columns at thoracic levels. The newer results in humans [12,21], showing long-term dramatic acute reductions in severe, chronic pelvic pain without effects on bladder or colon function, are convincing and consistent with much earlier findings on the effects of larger dorsal column lesions or commissural myelotomies at cervical levels for conditions such as phantom limb and other severe, chronic visceral pains [10, 12, 20, 22]. The admirable and heartwarming enthusiasm and caring attitude at the obvious potential of such surgery for relieving intractable pain is evident in the text of one of the most recent of these papers. Thus, Nautaet al. [21], reporting on the effects of a punctate lesion in the midline of the dorsal columns at T8 performed on a
Lesion Size
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39-year-old cachexic woman with insulin-dependent diabetes and severely disabled by severe pelvic pain due to extensive pathology of her bowel, bladder, and ureter induced by radiation given for cervical cancer, state (p. 540): At examination on postoperative Day 1, there were no new neurological deficits. The patient's vibratory, light touch, and proprioceptive sensation remained unchanged with only the mild changes already noted preoperatively and attributed to her preexisting diabetic neuropathy. Pain assessment ... indicated complete pain relief. Furthermore, the authors report that by 72 days after her surgery, the patient's morphine dose had been greatly reduced, she had gained appetitite and some weight (5 Ib) and "she was able to travel out of town, attend her daughter's school functions, and perform her daily household chores." Despite the development 4 months postoperatively of multiple pelvic fistulas that the authors attribute to complications of radiation in the context of diabetes mellitus, the patient remained relatively pain free. Thus, in summary, the authors were able to state that "At the time of this writing (10 months after the punctate myelotomy procedure), she has no complaints of any pain in the lower abdomen, and she continues to believe that the myelotomy eliminated her original pain without recurrence or new dysesthesias." This testimony is reminiscent of one by Leriche in 1939 [17], who, after performing in 1928 a "section of the posterior commissure" in one female patient that was completely and enduringly successful, then decided to "turn my attention in another direction in the problem of the treatment of pain (p. 470)." This direction consisted of "operations on the sympathetic." In reporting upon the results from nine patients, here is his enthusiastic and caring description of the results in one of the patients (p. 472): "A woman of 33 years of age was sent to the clinic on account of intolerable pelvic and perineal pain, with attacks of obstruction. A year previously, she had been subjected to two applications of radium for epithelioma of the cervix. For about ten months she appeared to be cured, when the pains appeared. She had to have an iliac colostomy, as a matter of urgency. This relieved her conditions considerably, but the pains persisted, and prevented any sleep. "On September 11, 1934, I advised Jung to remove the lower part of both lumbar ganglionic chains, and to resect the presacral nerve. "The result was remarkable. The pains disappeared. It was possible to stop using morphine,
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and the patient left the clinic overjoyed at being relieved of her pain. In December she developed a recto-vaginal fistula, but she had no pain. She slept well, took her food well, and busied herself about her house. In short, she led a normal existence, with the illusion of cure. And this state of well-being continued for four full months. Then she died very quickly from uraemia." There are at least two important conclusions to be drawn from these two similar case scenarios. First, we have multiple means to alleviate a patient's suffering. Second, the pains of both of the female patients were severely disabling and life-threatening, presumably due to the continuinq barrage of their nervous systems by information conveyed to it via nerves innervating their increasingly diseased pelvic organs. In that context, significant invasive procedures seemed warranted, regardless of potential "side" effects (sensorimotor in the former, autonomic in the latter). As stated earlier, this is the "context" for most of the patients in whom limited thoracic myelotomy has been successfully used. Now let us apply the above discussions to a case history.
EPIGASTRIC PAIN: A CASE HISTORY From January of 1989 until his death in 1995 at the age of 59, MarkA. Berkley, my best friend and husband of 30 years, suffered increasingly troublesome, worrisome, and severe, unrelenting, pounding epigastric pain that affected nearly all aspects of his and our family's and our social lives. For several years early on, numerous unpleasant, inconvenient, time-consuming, expensive, and sometimes invasive diagnostic procedures ruled out the heart. disease that ran in his family but failed to provide even one clue to the many experts attending him about the likely source of his pain until an adenoma at the head of his pancreas finally announced itself with jaundice more thanfour years later in August of 1993. During my husband's precancerous 1989-1993 period, small doses of ibuprofen, deliberately combined with music, cooking, gadget inventing and construction, model building, playing squash, romping with our dog, sailing and mountain climbing with his family, and absorption in his academic and technically demanding scientific research (brain mechanisms of vision) helped considerably, particularly when low doses of oxycodone were temporarily granted and added to the mix after invasive procedures, but his pains remained severe and preoccupying. In 1993, following Whipple surgery, which removed most of his pancreas and parts of surrounding organs, his pains remained, alleviated increasingly less successfully by the combinations of therapies described above (oxycodone was now deemed permanently safe)
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until his death two years later. However, for nearly 18 months after the surgery, despite his pain and fear of death, he continued to derive deliberately greater and greater pleasure in his old pursuits, such as skiing, hiking in the mountains, fussing about inventing and constructing all manner of scientific and household items big and small, and, during a 5-month teaching assignment in London in 1994, exploring by foot out-of-the-way boating facilities, art museums , bookshops, and all manner of obscure places. An important feature of this period was that his delight in these doings enhanced considerably our family's cohesiveness and pleasure in each other's company. The question arises here as to whether, at any time during the 6-year course of my husband's illness(es), a limited or punctate thoracic myelotomy should have been considered to relieve his pains. If his doctors or I had access to the information provided in this Focus article, including its reference to laudable new research indicating that dorsal column lesions in rats reduce pain behaviors in response to esophageal and pancreatic stimuli [6,13], my guess is that we might have strongly encouraged him to undergo this seemingly simple and effective mimimalist neurosurgical procedure (as dramatically illustrated so disarmingly on the cover of the March 1997 issue of the Journal of Neurosurgery [21] ) perhaps as early as 1992, when his pains had become almost continuous and dominating . Most certainly, however, it would have been considered in October 1993 several months after his Whipple surgery, because it had become clear by then that his epigastric pain would continue unabated , even with the higher doses of morphine still miserly and humiliatingly doled out at monthly intervals by his doctors. However, given the review above, consider what might have happened had he undergone such surgery at either of those times. From the analysis I provided in my editorial [1], the animal and clinical literature appears to indicate that the less the dominance and duration of severe and increasing visceral pathology, the greater the likelihood that damage of any sort to the dorsal columns would produce at least some of the sensorimotor side effects reviewed here above, especially if the lesion is more rostral and not performed as perfectly and carefully as the one described by Nauta et al. [21], thereby "accidentally" damaging parts of the dorsal horn or more lateral fibers. Thus, the development of such side effects would have been a distinct possibility for my husband, even in October 1993, in part because all tumor had been removed and he felt quite fit except for the pounding epigastric pain. For him, sustaining what might have seemed relatively minor sensorimotor deficits in a clinical setting would have been devastating to his everyday life, in which his delights were derived mainly
from activities that required dexterity, mobility, and complex muscle coordination of his hindlimbs and feet (eg, skiing, traveling, exploring difficult-to-get-to places, hiking in mountains). Even if those side effects had been "temporary," they would have used up a considerable proportion of the 18 months of relatively good health he had left to him. Given the Sophie's choice of the possibility of diminished pain with diminished sensorimo tor function in his legs, or the possibility of aggressively using his lively interests to add to the mix of his other therapies (eg, drugs and exercise , family activities, and music) to reduce the consequences of his pain, I am certain that at that time he would have preferred the latter. On the other hand, when his condition began to deteriorate rapidly during the last 5 months of his life as the tumor burden created significantly more abdominal visceral pathophysiology and robbed him of the ability to carry out his usual motor pursuits as therapy, it seems quite clear now that then , and only then, a limited thorac ic dorsal column lesion might indeed have been the best of the choices available to give him, like it has more recently for others in his condition, the relief of freedom from pain without the price of loss of other remaining functions.
CONCLUSIONS Table 1 updates another published in Reference 1, listing a vast , hopeful, and ever-increasing array of medical (column A), somatic (column S), and situational (column C) therapies that can be applied to people in pain. Although, as indicated in the Focus article, one might question the importance in clinical practice of one's . particular conceptualization of pain mechanisms, it can in fact influence how the clinician both gathers data from patients and uses the items in this table to devise treatment strategies. The fascicular conceptualization shown in Figure 1 of the Focus article reinforces traditional clinical approaches in which information is gathered mainly about the patient's morbid condition (eg, pain), and treatment consists of the application of one or only a few of the therapies listed in the table that may "work" for that type of pain condition (eg, severe chronic visceral pain). The "ensemble" conceptualization shown in Figure 2 encourages a more active cooperation between the patient and clinician , allowing the gathering of more complete information about the patient's life so that the patient and clinician can together develop a strategy of deliberate multitherapy; for example , two from column A, three from column S, four or more from column C, with the option of changing combinations if the items chosen are not effective enough or as the patient's condition or life situation changes. Thus, fascicular clinicians would be more likely to opt for limited myeloto-
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Table 1.
A growing list of therapies for pain
Somatic Interventions
Drugs Primary analgesics
NSAID acetaminophen opioids Other analgesics
Simple
heat/cold exercise massage vibration relaxation
a-2 agonists 13 adrenergic antagonists Minimally invasive physical therapy antidepressants anticonvulsants traction antiarrhythmics manipulation calcium channel blockers ultrasound cannabinoids TENS corticosteroids acupuncture GABAs agonists local anesthetics serotonin agonists Invasive
Adjuvants
antihistamines laxatives neuroleptics phenothiazines Routes
topical oral buccal sublingual intranasal vaginal rectal transfermal intramuscular intraperitoneal intravenous epidural intrathecal intraventricular
radiation therapy dorsal column stimulation nerve blocks neurectomy local ganglion blocks sympathectomy rhizotomy DREZ lesions punctate midline myelotomy limited myelotomy commisural myelotomy cordotomy brain stimulation brain lesions
Situational Approaches Clinician
education attitude clinical setting and arrangement Self
education meditation diet art, music, poetry, performing arts sports gardening aroma therapy religion Interactive
hypnosis biofeedback support groups advocacy groups networking self-help groups Structured settings
group therapy family counseling job counseling cognitivetherapy behavioraltherapy psychotherapy multidisciplinary clinic hospice
mies to treat various chronic visceral complaints than would ensemble clinicians, who would be more likely to opt for a combination of multiple approaches that include measures less invasive than damage to the spinal cord (however minimal) until the patient's situation changes enough where the prospect and impact of potential sensorimotor consequences would be minimized. With a fascicular approach, my husband might have been persuaded to undergo a limited or punctate upper thoracic myelotomy in October of 1993 that, while alleviating his pain, could have robbed him for a significant proportion of his remaining healthy time of many of the pursuits that brought him and his family so much pleasure. With the ensemble approach he had unwittingly been forced to develop for himself, however, such surgery would not have been considered for another 16 months at which time its application indeed could have been a blessing.
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Although the Focus article contains several misinterpretations of the publications of my group, I have chosen here to concentrate on the one that concerns me the most; that is, the misconception that my editorial [1] expressed "reservations about the utility of the surgical procedure" (ie, of limited or punctate thoracic myelotomy). It should be clear from the above discussion that it is not the procedure's "utility" about which I have reservations, but rather to whom and by whom it would be applied and when. I have two concerns. First, I worry that well-meaning fascicular clinicians less careful or competent than the enthusiastic few who have already done the surgery might be tempted by its seductive simplicity to consider offering it to a wider and wider range of patients with seemingly intractable visceral pain at any level of the body. Such a situation would increase the risks of iatrogenic effects. Second, I worry that patients made vulnerable by chronic disabling pelvic visceral pain that seems intractable when dealt with by well-meaning fascicular clinicians (and such patients would more likely be female than male; [2]) might be tempted and awed by the attraction and authority of a neurosurgical quick fix at a time when they might be more vulnerable to its as yet unknown, but distinctly possible, morbid consequences on other aspects of their daily lives. Acknowledgment I thank Dr. Anita Holdcroft for her help in the preparation of Table 1 (updated from Ref. [1J).
References 1. Berkley KJ: On the dorsal columns: translating basic research hypotheses to the clinic (Editorial). Pain 70:103107,1997 2. Berkley KJ: Sex differences in pain. Behav Brain Sci 20:371-380, 1997 3. Berkley KJ, Hubscher CH: Visceral and somatosensory tracks through the .neuroaxis and their relation to pain: lessons from the rat female reproductive system. pp. 195-216, 1995. In Gebhart GF (ed): Visceral pain, Progress in pain research and management, Vol. 5, GF IASP Press, Seattle 4. Berkley KJ, Vierck CJ Jr: Reduced retrograde labeling of diencephalic-projecting neurons in the gracile nucleus of the monkey tollowinq removal of dorsal column input. Exp NeuroI123:64-73, 1993 5. Davidoff RA: The dorsal columns. Neurology 39:13771385,1989 6. Feng Y, Cui M, AI-Chaer ED, Willis WD: Epigastric antinociception by cervical dorsal column lesions in rats. (Submitted) 7. Ganchrow D, Margolin JK, Bernstein JJ: Component analysis of hind limb behavioral alterations after damage to the rat dorsal funiculus. Exp Neurol 70:339-355, 1980
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8. Gilman S, Denny-Brown 0: Disorders of movement and behaviour following dorsal column lesions. Brain 89:397418,1966
18. Makous JC, Vierck CJ Jr: Physiological changes during recovery from a primate dorsal column lesion. Somatosens Mot Res 11:183-192, 1994
9. Glendinning OS, Cooper BY, Vierck CJ Jr, Leonard CM: Altered precision grasping in stumptail macaques after fasciculus cuneatus lesions. Somatosen Mot Res 9:6163, 1991
19. Makous JC, Friedman RM, Vierck CJ Jr: Effects of a dorsal column lesion on temporal processing within the somatosensory system of primates. Exp Brain Res 112:253-267, 1996
10. Gybels JM, Sweet WH: Neurosurgical treatment of persistent pain. Physiological and pathological mechanisms of human pain. Karger, Basel, 442 pp. 1989
20. Nathan PW, Smith MC, Cook AW: Sensory effects in man of lesions of the posterior columns and of some other afferent pathways. Brain 109: 1003-1 041, 1986
11. Hai J-X, Xu X-J, Aldskogius H, Seiger A, Wiesenfeld-Hallin Z: Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation. Pain 45:175-185,1991 12. Hirshberg RM, AI-Chaer ED, Lawand NB, Westlund KN, Willis WD: Is there a pathway in the posterior funiculus that signals visceral pain? Pain 67:291-305,1996 13. Houghton AK, Kadura S, Westlund KN: Dorsal column lesions reverse the reduction of homecage activity in rats with pancreatitis. NeuroRep 8:3795-3800, 1997 14. Hubscher CH: Comments on Berkley (letter). Pain 72:293292,1997 15. Leonard CM, Glendinning OS, Wilfong T, Cooper BY, Vierck CJ Jr: Alterations of natural hand movements after interruption of fasciculus cuneatus in the Macaque. Somatosens. Mot Res 9:75-89, 1992 16. Leonard CM, Vierck CJ Jr, Cooper BY: Social grooming after a dorsal column lesion in the Macaque. Soc Neurosci Abstr 12:497, 1986 17. Leriche R: The Surgery of Pain. London, Bailhere, Tindall and Cox, 1939
21. Nauta HJW, Hewitt E, Westlund KN, Willis WD Jr: Surgical interruption of a midline dorsal column visceral pain pathway. J Neurosurg 86:538-542, 1997 22. Sweet WH, Poletti CE, Gybels JM: Operations in the brainstem and spinal canal, with an appendix on the relationship of open to percutaneous cordotomy. pp. 11131135. In Wall PO, Melzack R (eds): Textbook of pain, 3rd ed., Edinburgh, Churchill Livingstone, 1994 23. Vierck CV Jr: Alterations of spatio-tactile discrimination after lesions of primate spinal cord. Brain Res 58:69-79, 1973 24. Vierck CV Jr: Tactile movement detection and discrimination following dorsal column lesions in monkeys. Exp Brain Res 20:331-346, 1974 25. Vierck CV Jr, Cohen RH, Cooper BY: Effects of spinal tractotomy on spatial sequence recognition in macaques. J Neurosci 3:280-290, 1983 26. Wall PO: The sensory and motor role of impulses travelling in the dorsal columns towards cerebral cortex. Brain 93:505-524, 1970