Recent clinical approaches to pain treatment

DON FLINN, M.D. CHRISTOPH YUNG, M.D.

Recent clinical approaches to pain treatment ABSTRACT: Recent years have seen a number of important

developments in pain research and treatment. Many new approaches have been developed to supplement the more traditional medical and surgical treatment for chronic pain. The following article reviews outcome studies of comprehensive pain treatment programs and examines the rationale, role, and effectiveness of some of the. new procedures being used, including biofeedback, acupuncture, transcutaneous electrical nerve stimulation, hypnosis, and behaviorally oriented programs. Research on the endorphins and its potential clinical value are also reviewed briefly. A steadily increasing interest in the treatment of pain has become apparent in recent years. Like the subject of death and dying, its prominence has been reflected in the Sunday supplement as well as in the scientific and medical literature. Certainly the problem of pain deserves this attention-few other conditions cause suffering, disability, and financial loss on so large a scale. The increased interest in pain

can be traced in large measure to several important developments. The first of these was the description by Bonica in 1953 of a coordinated multidisciplinary approach to the evaluation and management of chronic pain. 1 Since that time the establishment of pain clinics in which various specialists collaborate has become increasingly common. Among the specialists usually included are psychiatrists and psychologists who seek to identify per-

Dr. Flinn is professor and chairman and Dr. Yung is associate professor and chief of outpatient services, department of psychiatry, Texas Tech University School of Medicine. Reprint requests to Dr. Flinn, Department of Psychiatry, Texas Tech University Health Sciences Center, Lubbock, TX 79430. JANUARY 1982· VOL 23' NO I

sonality and learning factors that serve to maintain pain behaviors, as first described systematically by Fordyce and associates. 2 Then, in 1965, the "gate control" theory of pain, proposed by Melzack and WalJ,3 generated widespread interest and controversy, and since that time has stimulated highly productive research on basic pain mechanisms. Finally, the recent exciting discovery of the so-called endogenous opiates, such as enkephalins and endorphins, has held out further promise of increasing our fundamental understanding of pain. The primary focus of t~is paper will be on psychological aspects 9f pain and psychotherapeutic and other approaches currently used in pain management. Unfortunately, space does not allow review of our current understanding of the neurophysiology of pain.

Pain treatment programs The recognition that pain is a complex perception that is potentially modifiable at many levels of the central nervous system, coupled with the frequent failure of tradi33

Pain treatment

tiona 1 medical and surgical approaches to chronic pain treatment, has led to the recent development of a large number of programs that integrate behavioral and psychological components into a comprehensive rehabilitation program. Most employ a variety of modalities, including conventignal physical rehabilitation with gradually increasing activity quotas, relaxation training, hypnosis, didactic seminars, and family interventions. Group therapy of various types is used, including psychodynamic or cognitive restructuring approaches and the identification and modification of "pain games" as described by Sternbach.4 The approach itself seems less important than that it be consistent with the overall conceptual framework of the program. Since most chronic pain patients view their pain in physical terms and expect biologic interventions, it is necessary to present them with a plausible and acceptable conceptualization of the cognitive, affective, social, and learning components of the experience. Patients who are on narcoticlike analgesics have these drugs discontinued, using a fixed schedule with a gradually decreasing dose in a . vehicle that disguises the active ingredient. All of these approaches are carried out within a behavioral milieu' designed to systematically reinforce adaptive behavior through attention and praise while ignoring verbal or nonverbal painrelated behaviors. Programs vary with respect to whether physical modalities such as transcutaneous electrical stimulation and acupuncture are used concurren t1y. While some pain centers have reported on the immediate and long-term results of treatment, outcome is difficult to compare across 34

programs because of differences in the patient population, program characteristics, and criteria of success. In particular, it is difficult to tell which of the modalities used 1n the treatment programs might be effective, since most programs tend to use a "shotgun" approach. Various programs report differing success rates, with some claims of success in the 90% range. Considering the degree of disability of many patients in such programs, this seems to be a rather over-optimistic assessment of effectiveness.

There are quantifiable differences in the way various types ofpain are described, and patients with the same pain syndrome use remarkably similar words to communicate what they feel So far, it has not been established clearly which patients are most likely to be helped, which modalities are most helpful, or what level of improvement will be maintained on long-term follow-up. Of the first 130 patients in a comprehensive program at the Audie Murphy VA. Hospital in San Antonio, approximately one third reported significant decreases in pain intensity at the completion of the program, while two thirds showed overall improvement in social, occupational, and physical functioning, according to an oral communication from Larry Gaupp, Ph.D. This result is consistent with the assumption that such programs exert their beneficial effects primarily on the affective and motivational aspects of pain. Mayo study. The pain management program of the Mayo Clinic

group recently reviewed the oneyear follow-u p results of their first 200 patients to determine which types of patients were most likely to benefit from such a program. 5 Criteria were in three categories: modification of attitude, reduction of pain-related medication, and improvement of physical function. Data considered on each patient included personal and clinical history, medical-surgical diagnosis, subjective pain level at the start of the program, and MMPI scores. The subjective pain rating was based on a 10-point scale, with 0 being no pain and 10 the maximum imaginable. Of the 172 patients of this group who completed the program and were not excluded for methodologic reasons, 20% were classified as complete failures, while 20% were classified as successes with improvement in all three categories at the time of dismissal, which was sustained for one year. All of the successes reported improved work status, no medication except modest amounts of aspirin, and no furthertreatment for pain. Comparison of the two groups revealed no differences in age, sex, marital status, disability compensation, or the number of pain-related drugs being taken at the beginning of the program. Nor was there any difference in the pain site or neurologic and orthopedic diagnosis of the two groups. Hypochondriasis, depression, and hysteria scales on the MMPI were more elevated in the failure group, but the differences were not significant. In comparing the two groups, the following differenc~s were noted: I. Duration of pain and loss of work time were significantly greater in the failure group. Pain of less than three years' duration and work time loss of less than one year PSYCHOSOMATICS

were favorable indicators, whereas pain of five years' duration or more and work time loss of 18 months or more were unfavorable indicators. 2. The number of operations related to pain was significantly higher in the failure grou p, no operations or one operation being a favorable indicator and three or more operations unfavorable. 3. Pretreatment pain level was significantly higher in the failure group. Pain scale levels of 5 or less were favorable, whereas levels of 7 or more were unfavorable. 4~ Significantly higher drug dependency was found in the failure group and such dependency was an unfavorable indicator. 5. The items above, along with elevation of hypochondriasis and hysteria scales on the MMPI, were able to differentiate the two groups at a confidence level of .00 I. The authors speculated that these items may differentiate the two grou ps because they reflect factors involved in the complexity of chronic pain, such as motivation (duration of pain, work time loss), iatrogenic factors (operations, drug abuse) and sick role (secondary gain, chronicity, drug abuse, and perception of pain). This rating method would seem to be of practical value as a relatively quick method of assessing suitability of candidates for this type of program. Minnesota study. An outcome study reported by Roberts and Reinhardt from the University of Minnesota6 suggested that behavioral modalities alone may be as effective as programs using transcutaneous nerve stimulation, acupuncture, hypnosis, biofeedback, ahd the like. Based on stringent criteria of success including activity level, work, socialization, absence of compensation, and no hospitalJANUARY 1982' VOL 23 • NO 1

izations or prescription drug treatment, they found that 77% of their patients were functioning normally without pain medications from one to eight years following discharge from an eight-week behaviorally oriented inpatient rehabilitation program. They compared these results with the results of two other groups, composed of (I) patients rejected from the program because of compensation issues, poor motivation, or availability of other more appropriate treatment, and (2) patients who were acceptable for the program but who refused treatment. There was a striking difference in the outcome of the treated versus the untreated groups. Of 20 patients rejected for treatment, only one met the criteria for adequate functioning at followup, while none of the 12 patients who had refused treatment met these criteria. However, it is not possible to say if the results can be attributed to the program alone. The untreated group can hardly be considered a control, since it contained some applicants who had been rejected as unsuitable and others who by virtue of refusing the program may have been less motivated to change than the treatment group. Transcutaneous nerve stimulation

Transcutaneous electrical nerve stimulation (TNS) is being widely used in the treatment of chronic pain. Its use is directly related to the gate control theory of pain, since its rationale is based on the assumption that stimulation of large diameter fibers will close the gate to nociceptive input. In spite of the questions that have been raised about the theory as originally proposed, the treatment innovation

based upon the theory has been moderately effective. In a recent review of the status of the theory, WaIF states that a significa'nt number of patients with pain due to peripheral disease (but not central pain) have benefited from transcutaneous electrical nerve stimulation. He 'Cites one review that reports thaCof over 3000 pa tien ts from variQU,s centers, nearly one fourth expe,rienced more or less complete relief. Johannson and associates 8 studied the effect of high-frequency transcutaneous nerve stimulation in a series of 72 patients with chronic pain in an attempt to identify factors related to a positive outcome. Commercially available electrical stimulators were used, with impulses in the range of 80 to 100 hertz, and with electrodes positioned over painful areas or over main afferent nerve trunks. Treatments were applied three to six times daily for two to four days. The change in pain intensity after stimulation, expressed as a percentage of subjective pain relief, was calcula ted. Positive results were defined as between 20% and 100% pain relief for more than 30 minutes after stimulation. Approximately two thirds of the patients hqd between 50% and 100% pain relief within two hours after receiving stimulation, Endorphin levels were measured prior to treatment, since an earlier study had suggested that endorphin levels were lower in patients with organic pain syndromes than in those with psychogenic pain. In the patient group, 41 were diagnosed as having neurogenic pain, 23 as having somatogenic pain, and eight were believed to have psychogenic pain. About 50% of the patients in the study had "accept35

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a ble" pain relief, a finding consistent with other evaluations of electrical nerve stimulation in the treatment of chronic pain. Patients' subjective pain intensity did not significantly influence the outcome of treatment, but both type and localization of pain were significantly related to the result of treatment. The overall outcome was far better for neurogenic pain of mostly peripheral origin than for somatogenic organic pain without evidence of a neural lesion or for psychogenic pain. Pain in the extremities could be far more successfully treated than pain in midline structures. For neurogenic pain, only modest relief could be obtained in face and trunk neuralgias, such as trigeminal or postherpetic pain. There was a trend for patients with lower endorphin levels to have a better response to trea tinen 1.

Biofeedback In recent years, biofeedback treatment has been used for a variety of pain syndromes. There have been enough well-controlled studies to demonstrate that biofeedback is an effective treatment for tension headache. These studies were reviewed recently by Jessup and associates. 9 Most studies have shown that biofeedback treatment is about twice as effective as false biofeedback in reducing headache severity, as reflected by combined measures of intensity, frequency, and duration. Enthusiasm for biofeedback, however, must be tempered somewhat by studies showing that relaxation training is at least equally effective. There is some indication that combined treatment is more effective than either alone. Biofeedback is also used for the treatment of migraine, but here its

ra tiQnale is less clear. The most commonly used technique is hand warming using temperature feedback. This is based on the assumption that the painful dilated cerebral and extra cranial vessels in migraine are a reflection of widespread sympathetic dysfunction, which can be modified by learning to elevate hand temperature. Other techniques have also been used, based on a rationale inconsistent with this sympathetic over-reactivity hypothesis. The results of the better-controlled studies have failed to support the effectiveness of biofeedback treatment, although some isolated studies have been more positive. Even in those studies reporting effectiveness, most did not demonstrate that improvement was related to hand temperature change in the expected direction. Some success has been reported with techniques that condition temporal artery constriction, but it is not yet possible to give any final judgment about the effectiveness of biofeedback for migraine. Biofeedback has also been used in a wide variety of somatic, visceral, and musculoskeletal pain syndromes, including conditioning of hand temperature in Raynaud's disease and of gastric pH in peptic ulcer disease. However, the wide variation in rationale, technique, quality, and results makes any conclusions difficult at this time.

Acupuncture Acupuncture's effect is supposed to result from redistributing hypothetical energy within a number of major meridians of the body. As currently used in this country it is often in the hands of unorthodox practitioners, and the claims about its effectiveness sometimes challenge credulity. Millman,1O after a

comprehensive review in 1977, took a rather skeptical stand, and while acknOWledging reported benefits from large-scale uncontrolled clinical studies in well-known institutions, concluded that suggestion and placebo effect have substantial role~. He suggested that acupuncture's main indication may be for functional disorders. On the other hand, some wellcontrolled experimental studies have shown significant increases in pain threshold and tolerance. In one such study, using pain threshold of teeth to electrical stimulation, electro-acupuncture to a site on the hand produced significant analgesia. II A surface electrode over the same site had a nearly identical effect. This effect was later replicated in a different study, using needles inserted into the "Ho Ku" point in the web between the thumb and index finger and twirled. '2 There was no effect in a placebo medication group. Double-blind injection of naloxone and saline resulted in a decrease in the pain threshold to baseline for the naloxone group only. In another controlled study of the effect of electro-acupuncture using both genuine and pseudoacupuncture points, a consistent increase in pain tolerance was found for both, but the increase reached significant' levels only for the genuine points. 13 In a recent review of the role of acupuncture, Ulett,14 who believes it to be useful and effective for many chronic pain conditions, discussed possible mechanisms 'to explain its effects.

Hypnosis Despite its somewhat unsavory reputation, hypnosis has occasionally been used successfully as the only anesthesia for major surgical (continued)

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Pain treatment

procedures, including cesarean sections and cardiac surgery. Its effectiveness apparently depends less on the skill of the operator than on the ability of the subject to respond to suggestion. According to Hilgard,15 only about 10% of the population has a high degree of hypnotizability, as indicated by the ability to experience negative hallucinations. In one study of pain reduction through hypnosis in a grou p of highly hypnotizable subjects, two thirds achieved a 33% or more reduction in pain during a cold presS'or test, while of subjects rated as having a low level of hypnotic susceptibility, more than half had less than 10% pain reduction. 16 It would be natural to assume that hypnotic susceptibility might be related to placebo response. McGlashan and associates l7 studied this question by using an initial simulated hypnotic procedure to control for patient expectation, and found that the effect of hypnosis on pain could not be explained in terms of the subject's expectation, but was directly related to hypnotizability. The unhypnotizable subjects studied also derived some benefit from hypnosis, but since it W8.S approximately the same as that derived from placebo, it could be explained as a placebo effect of the hypnotic procedure. Because a large part of the population is unable to achieve any significant degree of hypnotic trance, it is likely that many patients who appear to respond to various hypnotically mediated treatments for smoking, overeating, relief of anxiety, and the like, are in fact responding to the placebo effect of the procedure. Although hypnosis is useful in some patients, its limited ability to significantly abolish chronic pain is JANUARY 1982· VOL 23· NO I

consistent with the Hilgards' thesis that its influence in pain is through the mechanisms of re-interpretation of the experience, time distortion, and displacement. ls

Description of pain Melzack and Torgerson 19 explored the subjective aspects of the sensory-discriminative and affectivemotivational components of pain. One hundred words that have been used to describe pain in the clinical literature were classified by subjects into sub-groups that described different aspects of the pain experience. This resulted in three major classes of words: a group describing sensory characteristics, a second group reflecting affective qualities such as tension and fear, and a group of evaluative words that labeled the overall subjective intensity of the experience. These three major classes could then be divided by raters into 16 sub-classes, each of which could then be ranked-ordered for intensity by physicians, patients, and student raters with good agreement. The resulting McGill Pain Questionnaire has demonstrated potential value as a diagnostic tool. It was administered to 95 patients with eight known pain syndromes, and in a multiple-group discriminant analysis, each type of pain was found to occupy a different region in the multidimensional space derived from the pain description. The differences among the constellations of words for the eight syndromes were statistically significant, and a subsequent computer analysis placed 77% of patients in the correct category. The authors conclude that there are appreciable and quantifiable differences in the way various types of pain are described, and that patients with the

same disease or pain syndrome tend to use remarkably similar words to communicate what they are feeling.

Endorphins Perhaps the most exciting area of research that may someday have far-reaching effects on pain therapy is that of central nervous system biochemistry. Brain peptides with opiatelike action were suspected to exist after Pert and Snyder20 demonstrated in 1973 that there were opiate receptors in the central nervous system. In 1975, Hughes and associates 21 isolated two different pentapeptides with opiate activity, which they called enkephalins. Shortly thereafter Ling, Burgus, and Guillemin 22 isolated two larger peptides of hypophyseal-pituitary origin with opiatelike activity. These peptides, which they called endorphins, contained 16 and 17 amino acids, respectively, in their structure. When the amino acid sequences of the enkephalins and the endorphins were established, it turned out that all were fragments of a larger peptide, beta-lipotrophin, which had been isolated from whole pituitary by C.H. Li in 1964, and for which no biologic activity had been recognized. Beta-lipotroph in itself turned out to be part ofa larger precursor molecule that also includes the hormone adrenocorticotrophin (ACTH). Beta-lipotroph in and ACTH are concurrently secreted in response to stress. The principal group of beta-endorphin-lipotrophin cells is in the basal medial hypothalamus, but it has also become evident that parts of the eNS other than the pituitary are able to synthesize and release opiatelike peptid~s. The opiate receptors and morphinelike peptides in the brain 39

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have been reviewed by Snyder. 23 On the basis of a similar distribution of enkephalin and opiate receptors in the brain, he concludes that enkephalin is the peptide involved in mediating the brain functions associated with the action of opiates. In preliminary studies, intravenous administration of enkephalin in rats is several times more potent than morphine, and does produce both tolerance and dependence in animals. Snyder cites evidence that opiates apparently act both centrally and peripherally. At the central level they decrease the affective component of pain. But they also increase the threshold to pain and elicit analgesia at the spinal cord level in animals with cord transections. In the spinal cord, opiate receptors exist primarily in the substantia geJatinosa on the axons of sensory nerves. The highest concentration of enkephalins has also been found to be contained in neurons whose cell bodies and processes reside

within the substantia gelatinosa. It is highly likely that research on endogenous opiates will lead to important advances in the pharmacologic treatment of chronic pain. In the meantime, there are some interesting developments with respect to drugs having mixed opiate agonist-antagonist properties. N alorphine, described by Lasagna and Beecher24 in 1954 to have both properties, was a potent and relatively nonaddictive agent. However, it could not be used as an analgesic because of dysphoric and psychotomimetic effects. A search for similar agents led to the development of pentazocine, the only such drug now on the market. Other effective mixed agonist-antagonist opiates not yet on the market in the United States include butorphanol, nalbuphine, and buprenorphine. The last-mentioned is the only one of the above that seems free of psychotomimetic side-effects, and it is now in use in Europe as an analgesic. It shows

promise as an alternative to methadone because it is thought to be nonaddictive, and a new drug application to the FDA for its use as an analgesic is expe'cted soon. COlJclusion

While the new treatment modalities and the current understanding of pain on which they are based have greatly expanded our ability to help chronic pain patients, the clinical approach must include more than technical procedures. Psychological factors such as developmental experience, ethnic and cultural patterns, personality, the effects of learning and family influences, and the role of depression and other psychiatric syndromes are no less important now than in the past. Considera tion of such factors is an important part of the diagnostic assessment of the patient, and specific modalities are most likely to be effective if applied within an individualized, comprehensive treatment program. 0

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9. Jessup BA, Neufeld RWJ, Mersky H: Biofeedback therapy for headache and other pain: An evaluative review. Pain 7:225-270, 1979 10. Millman BS: Acupuncture: Context and critique. Annu Rev Med 28:223-234,1977. 11. Anderson SA, Erickson T, Holmgren E, el al: Electro-acupuncture: Effect on pain threshold measured with electrical stimulation of the teeth. Brain Res 63393-396, 1973. 12. Mayer OJ, Price DO, Rafii A: Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone Brain Res 121 :368-372, 1977 13. Stewart 0, Thompson J, Oswald I: Acupuncture analgesia: An experimental investigation. Br Med J 1:67-70,1977. 14. Ulett GA: Acupuncture treatments for pain relief. JAMA 245:768-769,1981 15 Hilgard ER: Hypnotic Susceptibility. New York, Harcourt Brace & World. 1965. 16. Hilgard ER. Morgan AH: Heart rate and blood pressure in the study of laboratory pain in man under normal conditions and as influenced by hypnosis. Acta Neurobiol Exp 35741-759,1975. 17. McGlashan TH, Evans FJ, Orne MT' The

nature ot hypnotic analgesia and ptacebo response to experimental pain. Psychosom Med 31 :227-246, 1969. 18. Hilgard E, Hilgard J: Hypnosis in the Relief of Pain. Los Altos, Calif, Kaufman.n, 1975. 19. Melzack R, Torgerson WS: On the language ot pain. Anesthesiology 34 :50-59, 1971. 20. Pert CB, Snyder SH: Opiate receptor: Demonstration in nervous tissue. Science 179:1011-1014,1973, 21. Hughes J, Smith TW, Kosterlitz HW, et al: Identification of two related pentapeptides from the brain with potent opiate activity. Nature 258:577-579,1975. 22. Ling N, Burgus R, Guillemin R: Isolation, primary structure and synthesis of alpha-endorphin and beta-endorphin, two peptides of hypothylamic-hypophysial origin with mor· phinomimetic activity. Proc Nat Acad Sci USA 73:3942-3946, 1976. 23. Snyder SHe The opiate receptor and morphine-like peptides in the brain. Am J Psychiatry 135645-652, 1978 24. Lasagna L, Beecher HK: The analgesic effectiveness of nalorphine and nalorphinemorphine combinations in man. J Pharmacol Exp Ther 111 :356-363, 1954.

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