Pain Management in Functional Gastrointestinal Disorders

REVIEW

Pain management in functional gastrointestinal disorders

ANTONIO VIGANO MD,EDUARDO BRUERA MD

N INTERNATIONAL WORKING AVIGANO,EBRUERA. Pain management in functional gastrointestinal dis- panel recently defined functional orders. Can J Gastroenterol 1995;9(2):85-90. Pain is a common feature in A gastrointestinal disorders (FGID)asa functional gastrointestinal disorders (FGID). An abnormally low visceral sensory threshold, as well as a number of central, spinal and peripheral pain-modulating “variable combination of chronic or re- abnormalities, have been proposed for this syndrome. Clinical aspects of pain as- current gastrointestinal symptoms not sociated with irritable esophagus, functional dyspepsia, biliary dysmotility, in- explained by structural or biochemical flammatory bowel syndrome and proctalgia fugax are reviewed. Because of its abnormalities. FGID include symptoms unclear pathophysiology, pain expression is the main target for the successful as- attributed to the pharynx, esophagus, sessment and management of symptomatic FGID. The sensory, cognitive and af- stomach, biliary tree, small and large fective components of pain intensity expression need to be addressed in the intestine or anorectum” (1). The com- context of a good physician-patient rapport. A multidisciplinary team approach mon symptom among FGID is pain, is ideal for the smaller subset of patients with severe and disabling symptoms. Al- while other specific symptoms charac- though pharmacotherapy may target specific functional disorders, the role of be- terize the different functional symptom havioural techniques and psychotherapy appears much more important for pain complexes. management in FGID. Functional performance and quality of life improvement, rather than pain intensity, are the main therapeutic goals in these patients. Irritable bowel syndrome (IBS)isthe prototype of FGID in terms of preva- Key Words: Functional gastrointestinal disorders, Pain assessment and management, lence, physiopathology, clinical find- Quality of life ings and therapeutic opportunities (2). The description of IBS is beyond this Traitement de la douleur dans la maladie gastro-intestinale paper’s purposes. However, IBS will be fonctionnelle considered a model to describe the cur- RÉSUMÉ : La douleur est une caractéristique fréquente des troubles gastro- rent understanding of the physiopa- intestinaux fonctionnels (TGIF). Un seuil sensoriel viscéral anormalement bas, thology and treatment of pain in FGID. de même qu’un nombre d’anomalies sensorielles au niveau central, spinal et pé- riphérique ont été avancées pour expliquer ce syndrome. Les aspects cliniques de PHYSIOPATHOLOGY la douleur associés à l’oesophage irritable, à la dyspepsie fonctionnelle, à la dys- In an attempt to understand the motilité biliaire, au syndrome inflammatoire intestinal et à la proctalgie fugace causes and the mechanism of pain in sont passés en revue. À cause de sa physiopathologie imprécise, l’expression de la IBS, the features of visceral sensation douleur est la principale cible d’une évaluation et d’un traitement réussis des and clinical evidences for altered pain voir page suivante perception in the gastrointestinal tract have been extensively reviewed. Vis- Palliative Care Program, Edmonton General Hospital, University of Alberta, Edmonton, ceral sensation can be subdivided into Alberta two functional categories: nonpainful Correspondence: Dr Antonio Vigano, Fellow in Clinical Research, Palliative Care Program, Edmonton General Hospital, 11111 Jasper Avenue, Edmonton, Alberta T5K 0L4. Telephone conscious sensation which informs the (403) 482-8531 individual about the state of the gastro- Received for publication July 14, 1994. Accepted August 15, 1994 intestinal tract with sensations of full-

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TGIF symptomatiques. Les composantes sensorielles, cognitives et affectives qui conditions is the frequent association caractérisent l’expression de la douleur dans son intensité doivent être abordées with psychiatric illness, especially dans le contexte d’un bon rapport médecin-patient. Une approche pluridiscipli- mood changes, anxiety or somatization naire est idéale chez un sous-groupe de patients plus restreint atteints de disorders (7). Life threatening events, symptômes graves et invalidants. Bien que la pharmacothérapie puisse s’attaquer loss of a job or loved one, long-standing à certains troubles fonctionnels spécifiques, le rôle de techniques comportemen- stress and severe emotional upset ap- tales et de la psychothérapie semble beaucoup plus important pour le traitement pear to precede the development of de la douleur associée aux TGIF. L’amélioration du rendement fonctionnel et de la functional abdominal pain more fre- qualité de vie plutôt que le soulagement de la douleur sont donc les principaux quently than the onset of organic gas- objectifs thérapeutiques chez ces patients. trointestinal disease (8). Furthermore, a history of sexual and physical abuse was particularly common in women suffering from FGID (9). Those events ness, hunger, satiety and nausea; and modulating mechanisms the deregula- also seem to enhance symptom report- painful visceral sensation which in- tion may take place. ing and health care utilization espe- forms the individual about potentially An increased visceral sensitivity has cially for pain management. A psycho- noxious events such as irritation of the been shown by intraluminal balloon logical similarity has been found mucosa or serosa, gross distension of distension of the stomach in functional between persons having IBS who do not the viscus, torsion or traction on the dyspepsia. Similar findings have been consult a physician and normal indi- mesentery, forceful contractions and extensively reported in the colon and viduals (10). So far, psychosocial dis- ischemia. Nociceptors have not been in the esophagus for IBS patients. The turbances appear to influence, rather identified in viscera; noxious and non- distension-induced pain was never re- than directly cause, the greater sympto- noxious stimuli are identified within lated to an abnormal visceral compli- matic and physiological response to the central nervous system (CNS)by ance (5). In IBS patients, stressful stressor in FGID patients compared with their intensity of discharge. Further- stimuli seem to influence intestinal normal individuals (1). more, there is no specific pathway for motility and pain perception to a visceral afferents in the spinal cord. greater extent than in normal individu- CLINICAL ASPECTS OF THE Visceral and somatic inputs converge als. Conversely, those gut disturbances PAIN SYNDROMES in the same second-order neurons of so- may influence the central nervous sys- A description of all the symptoms matic sensory. Subsequently, visceral tem. IBS patients with balloon disten- characterizing FGID with the related di- pain is poorly localized and is accompa- sion in the colon experienced pain at agnostic approaches is beyond the nied by autonomic and somatic reflexes many extracolonic sites such as the scope of this paper. Only pain manifes- as frequently seen in FGID. shoulder, back and thigh. These find- tations in the major FGID, such as irrita- Pain modulation is accomplished by ings may suggest an alteration in vis- ble esophagus, functional dyspepsia, central, spinal and peripheral mecha- ceral pain discrimination and a biliary dysmotility, IBS and proctalgia nisms. The central structures play an facilitation of referred pain mecha- fugax, will be reviewed. important role in the processing of the nisms (3). Chest pain resulting from irritable sensory experience of pain. Descending Pain in FGID may be partly caused by esophagus may fall into three clinical inhibitory pathways can be activated a hypoactive CNS antinociceptive sys- manifestations: pyrrhosis or heart burn; by endorphins from the periaqueductal tem. A decreased level of cerebrospinal odynophagia or pain on swallowing; grey area of the brain. The conver- fluid beta-endorphins has been found and spontaneous pain. While pyrrhosis gence of various sensory inputs into the in patients with long-lasting functional or odynophagia may easily be attrib- same second-order neuron within the lower abdominal pain (6). However, uted to an esophageal disorder, sponta- spinal cord can facilitate or inhibit the the pain sensitivity for ischemia in this neous chest pain of esophageal origin is pain transmission as suggested in the population was not found to be signifi- more difficult to diagnose. In the ab- gate-control theory by Melzak and cantly increased as previously shown sence of other specific symptoms, be- Wall. Finally, inflammatory mediators, for upper abdominal pain in functional sides the irritable esophagus syndrome, neuropeptides released from afferent dyspepsia. The possible effect of a low one should consider gastrointestinal terminals (antidromic nerve stimula- level of beta-endorphins on pain (eg, peptic ulcer disease), cardiac (eg, tion) and smooth muscle tone may threshold may be enhanced or counter- angina pectoris) or musculoskeletal modulate the sensory function of vis- balanced by neuropsychological (eg, costochondritis) organic disease ceral receptors (3). mechanisms such as level of attention, (11). It has become apparent that pain in anxiety, depression and mood. Burning or gnawing pain at the epi- FGID is related to an abnormally low Even though the role of psychologi- gastrium is present in the majority of visceral sensory threshold (4). How- cal factors in the etiology of FGID is still patients suffering from functional dys- ever, it is still unclear where in the pain unclear, a common feature of these pepsia. Because of the frequent over- lapping of functional dyspepsia

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symptoms with those of classic peptic TABLE 1 TABLE 2 ulcers, ulcer and nonulcer dyspeptics Unidimensional pain assessment Multidimensional pain assessment have been identified. In nonulcer dys- Problems: Pain Neuropathic/Incidental pepsia, eating-related pain is frequent, Lack of disciplined assessment syndrome while nocturnal pain, male preponder- Misuse of pharmacological and Social Family/Financial/Cultural ance and family history appear to be nonpharmacological interventions Drug Dose/Rapid tolerance?/ less important than in peptic ulcer dis- Over-use of antinociceptive interventions Toxicity ease (12). and underuse of other interventions Patient Renal function/Psychological Increased drug-related toxicity distress, coping history/ Epigastric or right hypogastric pain Addiction/Cognition simulating the biliary colic of gall- (hypoalert/hyperalert?)/ stones, but without identifiable disease, Spiritual may be caused by disordered motility of the sphincter of Oddi. Pain in biliary dysmotility may be precipitated by fatty Classic model foods or codeine but is often spontaneous and sometimes nocturnal. Cancer pain syndrome Chronic benign pain syndrome Abdominal pain in IBS is generally Pain relief Functional improvement colicky and dull. Its location may be over the anatomical location of the co- Emerging model lon or extracolonic. The spasmodic at- tacks may start during or right after a Cancer pain syndrome Chronic benign pain syndrome meal, but the acute phase is mostly re- Pain relief ported 1 to 1.5 h after eating. The se- Functional improvement verity of abdominal discomfort may be related to different kinds of foods, even though exacerbation and relief of IBS Figure 1) The classic and emerging model of the cancer pain syndrome and the chronic benign pain pain are variable in different individu- syndrome als. Passage of flatus and bowel move- ments generally decrease the sympto- pain can be easily measured by subjec- and affective components modulated matology (2). tive assessments. Numerical, verbal by environmental contingencies...” Finally, severe pain occurring and visual scales provide an idea of the (14). Functional disorders from illness, around the anus during defecation, af- ‘quantity’ of the patient’s pain expres- level of cognitive function, positive ter coitus or spontaneously in the ab- sion. Those tools may be assimilated to history of addiction/alcoholism, drug sence of organic diseases is the a sphygmomanometer or to a glucome- tolerance and toxicity, environmental hallmark of proctalgia fugax. This pain ter that measures blood pressure or gly- stressors, psychiatric illness, impair- recurs in paroxysms during the day and cemia, respectively, by unidimensional ment in daily and social function, un- night, ceasing without residue in less and standardized criteria. conscious secondary gain, somatization than 10 to 20 mins. During these at- The intensity of pain, however, can- and other illness coping behaviours tacks syncope, priapism and a tight, not be considered a simple entity. A may contribute to the final ‘construct’, tender band across the lower rectum unidimensional approach considers which is the pain intensity expression. may be observed (13). pain expression a direct manifestation The multidimensional evaluation of of nociception (similar to a blood pres- physical, social, psychological and ASSESSMENT sure reading in hypertension or blood spiritual components of pain is neces- Pain production in FGID may be re- glucose determination in diabetes mel- sary for the management of both lated to three stages: nociception (con- litus). Such simplified assessment as- chronic benign and malignant syn- cerning the genesis of the noxious sumes that pain is always what the pa- dromes. Table 2 reports some of those stimulus); perception (related to the tient defines as pain, and that the dimensions. Therefore, a multidisci- central, spinal and peripheral modula- intensity the patient reports is 100% plinary team approach is useful, par- tions of the nociceptive input); and ex- nociception. This approach may lead ticularly for patients with severe and pression (representing the final proc- to lack of a disciplined assessment of disabling symptoms. essing of the sensory experience of the different dimensions of pain pain). Because the first and second expression, to misuse/overuse of MANAGEMENT stages cannot be assessed or monitored antinociceptive interventions and to un- Once diagnosis and a good rapport clinically, treatment will be aimed to deruse of nonpharmacological inter- between the physician and the patient decrease the pain expression. ventions (Table 1). have been established, an accurate set- It has been shown in both acute and Pain is “a multidimensional experi- ting of goals and instruments for pain chronic syndromes that the intensity of ence with sensory as well as cognitive control in FGID is possible. As shown in

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TABLE 3 pharmacological treatments to in- Comparison of cancer pain with chronic benign pain crease patient autonomy and function. Cancer pain patients Chronic benign pain patients These paradigms were based on a series Short survival Long survival of identified differences between the Multiple severe symptoms (cachexia, Pain-only symptom two syndromes (Table 3). However, in dyspnea, nausea) recent years it has become apparent Multiple drugs Few drugs that many of those differences are not Frequent cognitive failure Somatization, addiction, affective problems so clear-cut. The result has been an Mechanism: somatic, visceral, Frequent neuropathic mechanism emerging model based on a multidisci- neuropathic plinary and multimodal management Palliative care Seen by chronic pain clinics of both patient populations. Therefore, pharmacological, physical, psychologi- Cancer pain Chronic benign pain cal or behavioural treatments are all in- Mechanism of pain evident Mechanism less evident and predictable dicated as part of comprehensive pain Assessment of pain intensity Assessment of functional status (pain as illness) (ill patients) management in FGID. Focus on pain intensity and aggravating Discourage pain behaviour (maladaptive), factors reinforce rehabilitation PHARMACOLOGICAL Opioids main treatment Discontinue all possible drugs (antidepressants, APPROACH NSAIDs, opioids) Pharmacotherapy may play an im- Nonpharmacological treatments Emphasis on increased control (TENS, relaxation, portant role for targeting specific func- rare etc) tional disorders. ‘Antispasmodic’ drugs NSAIDs Nonsteroidal anti-inflammatory drugs; TENS Transdermal electrical stimulation are most frequently used to treat pain symptoms in FGID, even though a clear relationship between pain and gut mo- TABLE 4 tility has not been firmly established. Guidelines for the opioid use in chronic nonmalignant pain However, in view of the cholinergi- Establish the medical diagnosis underlying the pain cally mediated gastrocolonic response, Consider a recent/remote history of substance abuse the patient with recurrent abdominal Exclude any benefit from first line nonopioid analgesic and adjuvant drugs pain after meals may benefit from an Identify only one physician to prescribe opioids anticholinergic agent before meals (ie, Employ the World Health Organization ‘analgesic ladder’ principles for cancer pain 10 to 20 mg dicycloverine 30 mins be- management fore meals). Other antispasmodic Avoid short-acting (eg, meperidine) and agonist-antagonist (eg, pentazocine) opioids drugs, such as calcium channel block- Identify the dose associated with meaningful partial analgesia and no opioid toxicity ers, peppermint oil, naloxone and se- compromising comfort or function lective serotonin and cholecystokinin Advance to a higher step on the analgesic ladder whenever the previous has been unsatisfactory antagonist, have been proposed but re- Whenever a strong opioid is indicated, the oral morphine is convenient for titration. The quire more clinical trials before accep- starting dose should be 10 mg by mouth every 4 h. This dose should be increased once tance (15). or twice weekly by 25 to 50% until the desired effect is achieved Small doses of acetominophen may Include with ‘around the clock’ administration, the prescription of extra opioid doses as be useful in the short term while nar- required to treat breakthrough pain cotics are not particularly encouraged If there are no contraindications (eg, features suggesting abuse) the patient on a stable (14). Whenever opioids are indicated and effective dose of short-acting morphine preparation should be switched to a long-acting one (every 8 to 12 h) for the pharmacological treatment of Parenteral administration of opioids is strongly discouraged pain in FGID, the guidelines issued by Define a clear ‘contract’ between the prescribing physician and the patient regarding the College of Physicians and Surgeons opioid management in the Province of Alberta are recom- Reassess frequently the patient on opioids to evaluate analgesic efficacy and toxicity, mended (Table 4) (16). physical and psychological function and the occurrence of drug abuse-related Presently, neither the medical lit- behaviours erature nor clinical experience support long term opioid use for patients with chronic nonmalignant pain. There are no adequate controlled trials of these Figure 1, pain relief and functional im- respectively (14). The cancer paradigm drugs. The data appear to support the provement have been proposed as the proposed mostly pharmacological ap- use of empirical therapeutic trials in se- main outcome measurements of the pa- proaches based on a need to decrease lected patients, followed by carefully tient with the cancer pain syndrome pain expression, while chronic benign monitored long term therapy in those and the chronic benign pain syndrome, pain management emphasized non- who benefit (17). Specifically, patients

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with a history of alcoholism or drug ad- TABLE 5 diction, psychiatric disorders or somati- Multidisciplinary pain centre zation are particulary poor candidates Clarify the diagnosis. Review medical records and the need for further diagnostic studies or for opioid trials. invasive procedures Psychopharmacological agents such Improve pain control (eliminate pain if possible) through physical therapies: as antidepressants and anxiolytics seem Help the patient to be more comfortably active to be effective in some patients. Cen- Promote the use of alternative modalities other than potent medications tral analgesia, anticholinergic action With individually structured exercise programs, reduce the patient’s fear of reinjury on the gut and relief of depression or Teach proper body mechanics and postural awareness anxiety may provide symptom remis- Evaluate limitations and restrictions sion in FGID (1). Tricyclic antidepres- Improve psychological functioning: sants and fluoxetine are often indicated Define and address psychosocial issues influencing the chronic pain syndrome in chronic pain management because Relieve drug dependency of their brain serotoninergic action. Treat depression and its frequently associated insomnia They should be started in small doses Address primary and secondary gains from pain (eg, 50 to 75 mg amitriptyline at bed- Assess family system Strengthen support network (eg, personal, family and community) time, 20 mg fluoxetine in a single, day- Provide access to occupational and vocational rehabilitation and any other significant time dose) with a gradual increase to ef- health care personnel, and resolve disability when possible fective and tolerated therapeutic Communicate with the patient’s referring physician via discharge summary, telephone or levels. However, recent trials suggest personal meetings to obtain any information that will assist in the continued that tricyclic antidepressants are more management of the patient effective analgesics than specific Reduce inappropriate use of the health care system serotonin-reuptake inhibitors (18). Decrease the cost of medical care associated with chronic pain syndrome Benzodiazepine-type anxiolytics are Reproduced with permission from reference 22 occasionally helpful to relieve epi- sodes of stress-related symptom flares. Their long term use and combination Although beneficial in some cases, psy- laxation. Because of their simplicity, with anticholinergic drugs are not rec- choanalytic psychotherapy can be they are the primary treatment in the ommended (15). time-consuming and costly (21). The behavioural approach (1). techniques proposed by behavioural Hypnosis may reduce pain percep- NONPHARMACOLOGICAL psychologists appear efficacious man- tion in the gut, particularly in patients APPROACHES agement tools in dealing with chronic without associated psychopathological Physical therapy may play an impor- and intractable pain syndromes. Be- abnormalities. tant role for pain management in FGID. havioural treatments are mainly in- In biofeedback, skeletal muscle ac- Modalities such as heat, cold, tended to modify an abnormal illness tivity and other physiological functions soft-tissue massage and transdermal behaviour. This behaviour is defined as are monitored by audio or visual in- electrical stimulation (TENS) can aid in “the persistence of a maladaptive mode struments. The patients use this infor- decreasing or controlling pain. Exercise of experiencing, perceiving, evaluating mation to achieve a general state of re- programs are implemented to correct and responding to one’s own health laxation or to gain control over usually secondary dysfunctions. Patient educa- status, despite the fact that a doctor has unconscious physiological functions. tion in this context may enhance the provided a lucid and accurate appraisal All those noninvasive methods patients’ coping strategies with chronic of the situation and management to be may be performed by psychologists, disease, improve functional status and followed (if any), with opportunities behaviourally trained nurses, techni- prevent excessive stress on both the infor discussion, negotiation and clarifi- cians and physicians. The choice of volved and noninvolved body struc- cation based on adequate assessment of treatment depends on cost and avail- tures (19). all relevant biological, psychological ability (1). Among physical therapies, acu- and cultural factors” (21). The behavioural approach may help puncture has been used in chronic be- Behavioural techniques include re- motivated patients to reduce anxiety nign pain. Although its mechanism of laxation response training, autogenic and maladaptive illness behaviours. action is still unclear, acupuncture training, hypnosis and biofeedback, Productive behaviours can be restored plays a neuromodulating role in the with the contribution of some of the by those treatments, which finally en- mentioned stages of pain production pharmacological (eg, antidepressants) hance pain tolerance (21). (20). and physical (eg, massage, TENS) treat- Whenever pain and disability ap- Whenever psychosocial stressors are ments previously mentioned. Relaxa- pear refractory to simple pharmacologi- predominant, psychotherapy may be tion response and autogenic training cal interventions and basic counselling useful in diminishing their role in the lower sympathetic nervous system ac- by the treating physician, FGID patients pathogenesis of FGID symptomatology. tivity and produce skeletal muscle re- may be re-evaluated and managed by a

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aspects of pain associated with irritable rapport. A multidisciplinary team ap- multidisciplinary pain centre. The esophagus, functional dyspepsia, biliary proach is ideal for the smaller subset of underlined goals are reported in Table dysmotility, IBS and proctalgia fugax patients with severe and disabling 5 (22). have been reviewed. Because of its symptoms. Although pharmacotherapy unclear pathophysiology, pain ex- may target specific functional disor- SUMMARY pression is the main target for the suc- ders, the role of behavioural techniques Pain is a common feature in FGID. cessful assessment and management of and psychotherapy appears much more An abnormally low visceral sensory symptomatic FGID. important for pain management in threshold, as well as a number of cen- The sensory, cognitive and affective FGID. Functional performance and tral, spinal and peripheral pain- components of pain intensity expres- quality of life improvement, rather modulating abnormalities, have been sion need to be addressed in the con- than pain intensity, are the main thera- proposed for this syndrome. Clinical text of a good physician-patient peutic goals in these patients.

7. Song JY, Merskey H, Sullivan S, et al. treatment of the irritable bowel ACKNOWLEDGEMENTS: We ac- Anxiety and depression in patients syndrome. Drugs 1992;44:200-6. knowledge the Italian Association for Can- with abdominal bloating. Can J 16. College of Physicians and Surgeons of cer Research, Milano, Italy, for funding Dr Psychiatry 1993;38:475-9. Alberta. Guidelines for management of Vigano’s Research Fellowship with the Pal- 8. Creed F, Craig T, Farmer R. Functional chronic non-malignant pain. February liative Care Program at Edmonton General abdominal pain, psychiatric illness, and 1993. Hospital, Edmonton, Alberta. life events. Gut 1988;29:235-42. 17. Portenoy RK. Opioid therapy for 9. Drossman DA, Leserman J, Nachman chronic nonmalignant pain: current REFERENCES G, et al. Sexual and physical abuse in status. In: Fields HL, Liebeskind JC, 1. Drossman DA, Thompson WG. The women with functional or organic eds. Progress in Pain Research and irritable bowel syndrome: review and a gastrointestinal disorders. Ann Intern Management. Seattle: IASP Press, graduated multicomponent treatment Med 1990;113:828-33. 1994;16:247-87. approach. Ann Intern Med 10. Whitehead WE, Bosmajian L, 18. Max MB. Antidepressants as 1992;116:1009-16. Zonderman AB, et al. Symptoms of analgesics. In: Fields HL, Liebeskind 2. Snape WJ. Irritable bowel syndrome. psychologic distress associated with JC, eds. Progress in Pain Research and In: Cohen S, Soloway RD, eds. irritable bowel syndrome. Comparison Management. Seattle: IASP Press, Functional Disorders of the of community and medical clinic 1994;15:229-46. Gastrointestinal Tract. New York, samples. Gastroenterology 19. Yeh C, Shiell M, Lemke J, Volpe M. Edinburgh, London, Melbourne: 1988;95:709-14. Physical therapy: evaluation and Churchill Livingston, 1987;4:59-68. 11. Ouyang A. Chest pain, esophageal treatment of chronic pain. In: 3. Mayer EA, Raybould H. Role of neural spasm, and other functional disorders Aronoff GM, ed. Evaluation and control in gastrointestinal motility and of the esophagus. In: Cohen S, Treatment of Chronic Pain, 2nd edn. visceral pain. In: Snape WJ Jr, ed. Soloway RD, eds. Functional Disorders Baltimore: Williams & Wilkins, Pathogenesis of Functional Bowel of the Gastrointestinal Tract. New 1992;21:285-90. Disease. New York: Plenum Medical York, Edinburgh, London, Melbourne: 20. Ng LKY, Katims JJ, Lee MHM. Book Co, 1989:13-35. Churchill Livingston, 1987;1:1-16. Acupuncture: a neuromodulation 4. Costantini M, Sturniolo GC, 12. Thompson WG. Functional dyspepsia. technique for pain control. In: Aronoff Zaninotto G, et al. Altered esophageal In: Thompson WG, ed. The Irritable GM, ed. Evaluation and Treatment of pain threshold in irritable bowel Gut. Functional Disorders of the Chronic Pain, 2nd edn. Baltimore: syndrome. Dig Dis Sci 1993;38:206-12. Alimentary Canal. Baltimore: Williams & Wilkins, 1992;22:291-8. 5. Bradette M, Delvaux M, Stautmont G, University Park Press, 1979;12:153-72. 21. Pilowsky I. Abnormal illness behavior et al. Evaluation of colonic sensory 13. Thompson WG. Proctalgia fugax. (dysnosognosia) and the management thresholds in IBS patients using a In: Thompson WG, ed. The Irritable of chronic nonmalignant pain. In: barostat. Definition of optimal Gut. Functional Disorders of the Aronoff GM, ed. Evaluation and conditions and comparison with Alimentary Canal. Baltimore: Treatment of Chronic Pain, 2nd edn. healthy subjects. Dig Dis Sci University Park Press, 1979;10:125-30. Baltimore: Williams & Wilkins, 1994;39:449-57. 14. Turk DC, Fernandez E. Pain: a 1992;33:409-15. 6. Sorgensen LS, Bach FW, Christiansen cognitive-behavioural perspective. 22. Aronoff GM, McAlary PW. Pain P, et al. Decreased cerebrospinal fluid In: Watson M, ed. Cancer Patient Care centers: treatment for intractable b-endorphin and increased pain Psychosocial Treatment Methods. suffering and disability resulting from sensitivity in patients with functional Cambridge: The British Psychological chronic pain. In: Aronoff GM, ed. abdominal pain. Scand J Gastroenterol Society & Cambridge University Press, Evaluation and Treatment of Chronic 1993;98:763-6. 1991:1544. Pain, 2nd edn. Baltimore: Williams & 15. Pattee PL, Thompson WG. Drug Wilkins, 1992;34:416-29.

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