Chronic Nonmalignant Pain

DEFINITION

The International Society for the Study of Pain defines pain as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”¹ Chronic nonmalignant pain (CNMP) is defined variously as pain lasting 3 months or more, or as pain persisting beyond the time of expected healing. It can begin with trauma (e.g., back strain) or disease (e.g., pancreatitis) or can occur de novo (e.g., fibromyalgia, daily migraine).

PREVALENCE AND RISK FACTORS

One in 10 U.S. adults reports current pain that has lasted a year or more. Reviews have estimated the prevalence of severe chronic pain in the general adult population to be approximately 11%. It is our most common cause of disability.

Risk factors are biologic, sociologic, psychological, and environmental. It is more common in those with depression, anxiety, and substance-use disorders. Pain-associated disability is also more common in those from lower socioeconomic strata and in those who dislike their work or feel underpaid and unsupported at work. Risk is higher in certain vocations (e.g., truck driving), in survivors of overwhelming trauma (e.g., childhood abuse, natural disasters, combat), and in those genetically sensitive to noxious stimulation. Conditions commonly associated with CNMP include spine disease, headache disorders, fibromyalgia, neuropathies, and arthritis.

PATHOPHYSIOLOGY

Pain Biology

Some of the mystery surrounding chronic pain derives from concepts of nociceptive pain, which imply a strong relation between peripheral stimulation and pain perception. Pain is seen as an analogue representation of some event. Because of reliance on this acute pain model, when a patient complains of severe pain and no appropriate pathology is located, it is suspected that the complaints are not valid or that the workup missed something. In fact, excellent health does not preclude severe pain.

Pain is more a creation of the nervous system than a gauge of nociceptor activation.^2,³ Nociceptive afferent signals are subject to marked attenuation and amplification by descending tracts that have their action at the dorsal horn. Further, the presence of prolonged nociceptive stimulation, inflammation, or nerve injury can lead to sensitization of pain transmission fibers, death of inhibitory cells, loss of tonic inhibition, and structural neuroplastic changes. Activation of immune cells, including glia, previously believed to have only structural roles, produces exaggerated, widespread, and mirror image pains.

Pain facilitatory cells in the medulla fire in response to cortical processes, such as vigilance. In animals, simply anticipating a pain and expecting it to be important are sufficient to activate “on” cells, that initiate amplifiers before the pain stimulus has begun. Opioid withdrawal also activates these cells, explaining the associated muscle and bone pain.

Genetic factors modify pain perception and response to endogenous and exogenous opioids. Several single-nucleotide polymorphisms produce greater or lesser pain sensitivity. Imaging shows that persons reporting high or low pain in response to a standard stimulus demonstrate correspondingly high or low activation of the somatosensory cortex, anterior cingulate gyrus (a likely index of affective components of pain), and frontal cortex. The conclusion is that those who report unusual pain actually experience it, absent incentives for misrepresentation.

Patients with idiopathic chronic back pain, whiplash, and fibromyalgia, conditions often believed to be exaggerated or psychogenic, show evidence of central sensitization, again suggesting that their pain is genuine but not due to peripheral structural pathology.

Sensitization also leads to visceral hyperalgesia, which accounts for much obscure abdominal, pelvic, and chest pain. Interestingly, visceral hyperalgesia is easier to elicit in rats made anxious by genetic selection or by early maternal separation. These pain syndromes often respond to agents used for neuropathic pain, such as tricyclics or pregabalin.

Pain Psychology

Although psychological factors are rarely believed to cause pain, they dramatically modulate associated suffering and dysfunction. It has long been known that vigilance, expectation of pain, and reinforcement of pain behavior increase pain behavior, and it has now been demonstrated that these factors increase cortical activation associated with experimental pains. Conversely, distraction reduces pain.

Cognitive Issues

Functional impairment that greatly exceeds pathology is not necessarily psychogenic (Box 1). Patients commonly interpret pain as a sign of fragility, leading to unwarranted self-protection and inactivity. The resulting deconditioning causes minor activities to become painful, creating a cycle of escalating pain and disability.

Box 1 Toxic Cognitions in Pain

Physical fragility

Catastrophizing

Personal helplessness

External blame

Maladaptive cognitions play a central role in pain disorders. They tend to be automatic and thus not examined for validity, include such catastrophic interpretations as “the nerves are being crushed” or “these exercises must be tearing something loose,” which increase pain and disability.

Personal beliefs in self efficacy versus powerlessness are critical determinants of success in coping with chronic pain. Those who perceive events as a consequence of their own behavior tend to have better mood and function, whereas those who perceive events as due to other people or fate have more depression, anxiety, and dysfunction. The concept of learned helplessness also explains much impairment. A person who perceives himself or herself to be helpless is likely to stop trying entirely, leading to increased disability, depression, and ultimately pain.

Conditioning

Operant conditioning refers to the process by which forms of behavior increase when reinforced and extinguish when not reinforced. Plainly, animal life is contingent on a predisposition to selectively repeat behavior that leads to positive results. Reinforcement influences the extent of pain behavior and sick-role behavior. Although the sick role leads to multiple losses, including income, socialization, sexual function, and self esteem, it also can lead to care from others, a secure income, narcotics, and escape from a noxious work environment. Operant conditioning might explain the generally worse function and therapeutic outcomes seen in patients who are receiving pain-related disability income.

Reinforcers are time dependent, such that immediate weak reinforcers can overcome delayed stronger ones. This explains much maladaptive pain behavior: Actions that initially provided benefit persist after they have become liabilities. Neuroimaging suggests that reinforcing pain behavior can increase its actual perception.

Psychiatric Comorbidity

Although prevalence of comorbidity (Box 2) varies with population, the most common psychiatric disorders in chronic pain are depression, anxiety disorders, substance-use disorders, and somatoform disorders.⁴ Conditions such as schizophrenia and mania are relatively uncommon.

Box 2 Psychiatric Disorders Commonly Associated with Chronic Nonmalignant Pain

Personality disorders

Most patients disabled with chronic pain have substantial anxiety, and nearly 30% meet criteria for generalized anxiety disorder. Posttraumatic stress disorder and panic are also common. Anxiety sensitivity characterizes people who misinterpret the normal physiologic changes of anxiety as harbingers of medical catastrophe, such as a stroke. It is associated with chronic pain and with increased response to experimental pain.

The prevalence of depression in pain clinic patients is 30% to 84%. Mood strongly modulates pain, and simply reading sad stories or humorous ones alters pain threshold and tolerance, as does mood induction via hypnosis. In prospective studies, pain predicts the onset of depression, and depression predicts the onset of chronic pain, and they do so to approximately the same degree.

Identifying prescription drug addiction can be challenging, yet critical, because satisfactory management of chronic pain is unlikely in the addict (Box 3). Many hallmarks of addiction to recreational substances (driving citations, cirrhosis, work absenteeism, illegal behavior) are likely to be absent or attributed to pain. Official nomenclature relies heavily on the criteria of tolerance and physical dependence for diagnosing addiction. Although often appropriate for recreational substances, these criteria are not useful for prescribed analgesics. Structured interviews in a rehabilitation hospital identified 23% with active misuse or dependence and 9.4% in remission.

Box 3 The 3 Cs of Addiction

Loss of Control

Craving or preoccupation

Use despite Consequences

In pain disorder—classified as a somatoform disorder in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV-TR)—psychological factors are “judged to have important roles in the onset, severity, exacerbation, or maintenance of pain.”⁵ Other conditions involving physical symptoms or preoccupation with them that cannot be explained medically include somatization disorder, conversion disorder, and hypochondriasis. There is compelling evidence that major traumatic events, including childhood abuse, combat trauma, and natural disasters, often lead to a plethora of physical complaints, including pain, without identifiable medical pathology. Such traumas likely also augment the symptoms of pain that have a medical basis; this, however, is more difficult to establish.

Most studies of personality in CNMP lack pre-pain personality assessment data, and pain changes personality. Those trapped in the sick role often demonstrate inordinate regression and dependence not previously present. Nevertheless, personality disorder impedes coping with the stress of CNMP, thus leading to inordinate dysfunction. Additionally, traumas that damage personality also often lead to functional physical symptoms.

SIGNS AND SYMPTOMS

CNMP is not only a perception. CNMP is often associated with impairment in function that encompasses nearly all activities (Box 4). Patients not uncommonly spend upward of 20 hours per day reclining. Such a person reporting a back pain level of 7 of 10 is a far different clinical challenge than is a person whose pain is 7 of 10 but who maintains employment, socialization, and self care.

Box 4 Signs and Symptoms in Chronic Nonmalignant Pain

Sleep disruption is the rule in CNMP patients and is generally attributed to pain. However, counterintuitively, animal and human studies confirm that insomnia is more likely to exacerbate pain than pain is likely to exacerbate insomnia. Consequently, sleep disorder should be addressed specifically, with the expectation that its improvement can reduce pain.

Pain should be quantified (0 = no pain, 10 = the worst pain you can imagine) and characterized as to quality, timing, and relieving and exacerbating factors; however, this is not sufficient to characterize the symptoms. Function must also be assessed, along with emotional status and sleep.

These factors are most economically assessed and monitored over time by a simple self-report scale such as the Pain Disability Index or a similar scale of the clinician’s own devising (Fig. 1).

Figure 1 Status report for pain mood, function, and sleep.

DIAGNOSIS

Diagnostic signs and symptoms of the conditions that underlie CNMP are addressed in their respective chapters. The Institute for Clinical Systems Improvement has prepared guidelines for CNMP assessment and management,⁶ a summary of which is available online.⁷

Typical Characteristics

Several characteristics of the diagnostic workup in CNMP are noteworthy. First, it is to be expected that complaints often outweigh physical (and imaging) findings. Laboratory studies are often completely normal. This is because much of the discomfort of CNMP is due to neural sensitization and not peripheral pathology. Thus, after several episodes of pancreatitis, it is common to have persistent pain without laboratory abnormalities. Those with sickle cell disease develop pain between crises. Sciatica persists after diskectomy. Joints hurt when synovitis has resolved and acute-phase reactants have normalized.

Psychogenic pain is often suspected on the basis of nonphysiologic findings, such as Waddell’s signs in back pain (Box 5); however, these can be present even when unambiguous pathology explains the complaints. Inconsistencies are of much greater diagnostic import. Symptoms and signs can be inconsistent with anatomy (a patient presses with the “paralyzed” leg but not with the normal one). They can vary over time or with audience (a patient’s limp is much worse in the presence of a spouse).