Chronic Pain Syndrome

Chronic Pain Syndrome


Pain is as old as human experience, and in fact predates it as the experience of pain can be documented in most other species. Its name derives from Poine or Poina, the daimona or spirit of revenge and retribution, whose duties included punishing mortals who had angered the gods. The effects of Poina’s chastisement are described in the dramas of Aeschylus in the 5th century BCE. The Romans renamed her Poena and promoted her to demigoddess, and her name survives in the legal subpoena as well as the clinical symptom of pain. Most ancient cultures ascribed pain at least in part to human folly or wrongdoing, and ritual expiation was attempted in various ways (Parris & Johnson, 2008).

The ancients recognized an association between unhappiness and pain: in the Odyssey, Homer described the use by Telemachus of an anodyne that may or may not have been opium, in order to assuage his worries and relieve his pain (Booth, 1996). Plato felt that pain was an emotion and not a sensation, and pain was not included in the 5 senses described by Aristotle. Hippocrates, on the other hand, felt that pain was due like melancholy to imbalance of the humors, although he localized the sensation of pain to the heart rather than to the brain. Some ancient healers did ascribe painful conditions to brain disease, and trepanation of the skull was widely practiced for headache as well as mental disorder from Neolithic times onward, advocated in some cases by Hippocrates and his disciples and technically refined by the Roman Galen. At the same time or earlier, the Egyptians introduced electrical treatment of painful conditions, by applying eels fished from the Nile for that purpose. All of these ideas can be found in later approaches to the treatment of chronic pain (Meldrum, 2003).

A huge literature regarding pain and its assessment and treatment developed in the subsequent centuries, with increasing attention to the relationship between psychological state and character, intensity and chronicity of pain (Melzack & Katz, 2004). Wilhelm Griesinger proposed in 1845 that mental and physical pain were physiologically the same, the chief difference being that physical pain could be accurately localized. Freud’s teacher, the anatomist Theodor Meynert, suggested that chronic depression be analogized to chronic pain and termed “psychalgia”. Freud and Breuer recognized in their hysterical patients “the associative connection between physical pain and psychical affect” (Sharp & Keefe, 2006). Both Kraepelin and Bleuler noted apparent insensitivity to pain in their studies of schizophrenia (Bonnot, Anderson, Cohen, Willer & Tordjman, 2009).

Psychoanalysis from Freud to the present day has largely focused upon the symbolic character of chronic physical pain (Taylor, 2001). Engel (1959) proposed that, although pain may originate from external injury it can develop in “pain-prone” individuals into an independent entity with psychological symptoms. The current consensus does not support a psychodynamic predisposition to chronic pain, but it is generally agreed that persistent or disproportionate pain may reflect the influence of psychiatric factors, and may be amenable to psychopharmacological or psychotherapeutic treatment (Otis & Hughes, 2010).

Clinical Features

Recent population surveys suggest that 86 million or more Americans have some type of chronic pain (Moskowitz, 2002). Pain is currently the leading reason for primary care office visits, and accounts for more than 20 per cent of physician visits and 10 per cent of prescriptions (DeBono, Hoeksema & Hobbs, 2013). Chronic pain costs approximately $100 billion per year in medical expenses, lost productivity and loss of income. Productivity loss alone was recently estimated to cost $61.5 billion annually, about 75 per cent from impaired work performance due to pain. The most common type of pain, that of the low back, will affect 50 to 85 per cent of Americans during their lifetimes (Stewart, Ricci, Chee, Morgenstein & Lipton, 2003). Despite these substantial costs, there was not agreement until recently on a definition of pain generally, and of chronic pain particularly.

There is wide acceptance of the International Association for the Study of Pain definition of pain as “an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (Bonica, 1979). There is common but less general acceptance of the definition of chronic pain as that lasting more than 3 months; it has also been suggested that pain of 30 days or less duration is acute pain, while subacute pain lasts from 1 to 6 months and chronic pain persists for more than 6 months. Another definition has been pain that “extends beyond the expected period of healing” (DeBono, Hoeksema & Hobbs, 2013).

Chronic pain syndrome is actually a constellation of pain syndromes that is generally refractory to strictly medical management. A wide variety of musculoskeletal, neurological, urological, gastrointestinal, gynecological and cardiovascular disorders can manifest persistent pain. These patients appear to have in common demonstrable psychiatric comorbity, chiefly depression, and an increased incidence of familial chronic pain and known antecedents to psychiatric disorder such as abuse, neglect and familial substance use disorders. Patients also frequently manifest the ‘6 Ds” described by Sternbach (1977): dramatization of complaints, drug misuse, dysfunction or disuse of the painful part(s), dependency, depression and disability.

Chronic pain has been suggested to be a learned behavioral response, with an initial noxious cause for pain resulting in pain behavior that is internally or externally rewarded and thus reinforced, and which comes eventually to recur without a noxious stimulus (Davoine, Godinat, Petite & Saurer, 2013). At the same time, painful conditions can spontaneously develop generality, persistence and the clinical features of allodynia (pain evoked by a normally innocuous stimulus) and hyperpathia (markedly accentuated pain with a nociceptive stimulus) through the mechanism of central sensitization (Meeus & Nijs, 2007).

Psychiatric Comorbidity

Depression is the predominant psychiatric condition comorbid with chronic pain. Several large series of primary care patients and the general population suggested that psychological distress caused heightened awareness of physical symptoms, resulting in both pain and negative emotions (somatosensory amplification), in pain patients and those without chronic pain. Depression was predicted more by the extent to which pain interfered with the activities of daily life than by the reported intensity of the pain. Vegetative symptoms such as sleep disturbance or lack of energy were more common in pain patients than guilt or social isolation, and a proportion of chronic pain patients had initial psychological distress and disability but improved within 2 months after the onset of pain (von Korff & Simon, 1996). Prevalence rates for depression in chronic pain patients have ranged from 10 to 100 per cent according to patient report, and between 30 and 55 per cent when standardized diagnostic interviews were used (Banks & Kerns, 1996). Using DSM-4-TR diagnostic criteria, major depressive disorder could be found in 27 per cent of patients with chronic pain in primary care clinics (Bair, Robinson, Katon & Kroenke, 2003).

Major depression and chronic pain share many symptoms, such as fatigue, sleep disturbance and impaired attention and memory. False positive diagnoses of depression in pain clinics have been suggested to result from these common symptoms, but it has also been argued that the risks of false positive diagnoses of depression in pain patients are outweighed by the risks of missing remediable depression and the potential benefits of antidepressants for chronic pain (Cassem, 1990). The Diagnostic and Statistical Manual of Mental Disorders has historically recommended that somatic symptoms be ascribed to depression unless they can clearly be accounted for by a general medical disorder (American Psychiatric Association, 2000). Such an “inclusive” method led to the diagnosis of major depression after semi-structured diagnostic interviews in 35 per cent of chronic pain patients, while an “etiological” method, in which depressive symptoms caused by medical problems were not counted toward a depression diagnosis, identified major depression in 19 per cent. A “substitutive” approach, in which somatic symptoms were replaced by non-somatic alternatives, was positive in 30 per cent (Wilson, Mikail, D’Eon & Minns, 2001).

Comorbidity with other psychiatric disorders has been reported, particularly in studies from tertiary pain centers or inpatient units. The chief associations have been with anxiety, somatoform, personality and substance use disorders, and it has been suggested that state-dependent stress may activate various kinds of previously-dormant diathesis in chronic pain patients (Dersh, Polatin & Gatchel, 2002). The relationship between pain and psychiatric disorders in the general population has been studied in the National Comorbidity Survey (Kessler, McGonagle, Zhao, Nelson, Hughes, Eshlerman, Wittchen & Kendler, 1994)and its subsequent replication. A significant association between chronic arthritis pain and mood and anxiety disorder, particularly panic disorder and post-traumatic stress disorder, was found by a combination of self-report and structured interview; the presence of a single psychiatric disorder was not associated with disability from pain, but pain disability was significantly more likely with multiple psychiatric conditions (McWilliams, Cox & Enns, 2003).Thirty-five per cent of chronic back pain patients in the replication study had mental disorders, with anxiety disorder as common as mood disorder; substance abuse was not significantly correlated with spinal pain (von Korff, Crane, Lane, Miglioretti, Simon, Saunders, Stang, Brandenburg & Kessler, 2005).


Suicidal ideation and attempts are often a concern in the treatment of intractable pain. Only about 4 per cent of suicides are related to terminal illness, and most patients with such illnesses express the desire to live as long as possible (Hendin, 1999). Of the patients requesting physician assistance with suicide or receiving physician help in terminating life, however, severe pain and pain-related disability were the most frequent reasons, and about half were also depressed (Meier, Emmons, Litke, Wallenstein & Morrison, 2003). A review of 18 studies of suicidality and chronic pain found that pain severity and duration and comorbid depression were the principal risk factors for suicidal ideation or attempts (Fishbain, 1999). Some studies have correlated suicidality with pain severity (Smith, Perlis & Haythornwaite, 2004), while others have found suicidality to be related to presence and severity of depression rather than degree or persistence of pain (Fisher, Haythornwaite, Heinberg, Clark & Reed, 2001). A larger study of tertiary pain patients which assessed suicidal predilection and history in detail found that family history of suicide and intractable abdominal pain of indeterminate cause were strongly correlated with suicidality, while neuropathic pain even when severe was negatively correlated.and there was no relationship between suicidality and pain severity, pain duration or depression. This suggested that patients with pain of unknown cause may catastrophize or feel that pain is beyond their control, which predispose to suicidality (Smith, Edwards, Robinson & Dworkin, 2004).


The management of chronic pain syndromes is multifaceted and usually multidisciplinary. The goal is modulation of pain severity, cessation of reinforcement of pain behavior, restoration of function as much as possible, improvement in quality of life, reduction of medication use and avoidance of relapse of pain symptoms when subsequent stress occurs. This usually involves physical and occupational therapy, medical management and psychological therapy, and may be enhanced by the methods of alternative, complementary or integrative medicine.

Physical therapy modalities recommended for chronic pain include stretching exercises, massage, hot and (possibly) cold applications, ultrasound, osteopathic or other manipulation and transcutaneous electrical nerve stimulation (TENS). Controlled studies suggest that exercise regimens have an advantage over TENS and other modalities (Martin, Torre, Aguirre, González, Padierna, Matellanes & Quintana, 2014). Occupational and recreational therapy has been shown to increase patient involvement in the treatment process, and to facilitate desensitization that allows further increases in activity (Sanfakioglu, Gülezant ,A., Güzel, E., Güzel, S. & Kiziler, 2014).

Psychophysiologic therapy has been shown in open and controlled trials to reduce pain severity and disability. This includes biofeedback, relaxation training with either progressive muscular relaxation or autogenic training and stress management techniques (Tang, Salkovskis, Hodges, Soong, Hanna & Hester, 2009). Acceptance and commitment therapy (ACT0 and cognitive behavioral therapy (CBT) are both effective for chronic pain, improving pain interference and mood, but patients were more satisfied with ACT than CBT in a comparative trial (Weatherell, Afari, Rutledge, Stoddard, Petkus, Solomon, Lehman, Liu, Lang & Atkinson, 2011). An online counseling and support produced significant improvement for treated pain patients over controls in pain severity, interference from pain, emotional burden, catastrophization and fears about pain, which persisted for at least 14 weeks after the sessions (Ruehlman, Karoly & Enders, 2012).

Medication management has particularly involved opioids, which often cause problems and are sometimes necessary to use even when they do (Lembke, 2012). There is a large and growing literature documenting the efficacy of other drugs, usually approved in this country for indications other than chronic pain. Antidepressants are widely used, and the combination of these with psychological therapy has been shown to be more effective than drug treatment alone (Kroenke, Bair, Damush, Wu, Hoke, Sutherland & Tu, 2009). Transdermal buprenorphine, has shown analgesic efficacy, amelioration of mood and return to former activities in elderly patients incapacitated by chronic pain (Gianni, Madaio, Ceci, Benincasa, Conati, Franchi, Galetti, Niedu, Salani & Zuccaro, 2011). Botulinum toxin A has also been found to have analgesic efficacy with minimal adverse effects in chronic pain (Rannoux, Attal, Morain & Bouhassira, 2008). Anticonvulsants are widely used for chronic pain, with controlled-trial evidence of moderate strength in support of gabapentin and pregabalin (Moore, Wiffen, Derry & McQuay, 2011). Chronic pain is also the most common reason for patients to seek care at facilities offering alternative, complementary or integrative medicine, and a large long-term multi-center observational study has recently demonstrated significant improvements in pain severity, mood, quality of life, sleep quality, perceived stress and measures of well-being with personalized and non-standardized “holistic” treatment regimens (Abrams, Dolor, Roberts, Pechura, Dusek, Amoils, Amoils, Barrows, Edman, Frye, Guarnieri, Kligler. Monti, Spar & Wolever, 2013).


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