IN LIGHT OF THE OPIOID EPIDEMIC, THE MEDICAL community is paying increased attention to pain. The annual volume of publications found under a PubMed search for “chronic pain” doubled in the decade between 2006 and 2016 and increased nearly fivefold in the 20-year period prior to 2016. In 2011 the Institute of Medicine published a landmark assessment entitled “Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research,” that outlined current shortcomings in pain.¹ Most recently the consequences of opioid use and misuse have garnered substantial attention.²

These developments likely reflect, among other factors, the burden of disability due to pain and an evolving understanding of pain as a disorder. Evidence of the former exists in the 2013 Global Burden of Disease study, in which seven of the most common chronic conditions worldwide were primary pain conditions.³ Evidence of the latter comes from a large body of theoretical and experimental work, dating back to the mid-twentieth century, indicating that chronic pain (generally longer than 3 months’ duration) can be associated with changes throughout the central nervous system that are remote from external pain generators and may serve to sustain pain, distress, and disability independent of such generators. From the perspective of a specialist in physical medicine and rehabilitation (PM&R), chronic pain is a common cause of disability, loss of independence, and loss of life roles.

As research and clinical practice in pain have grown, the classification of painful conditions has been re-evaluated. The taxonomy of pain is still an evolving process that reflects these trends. In this chapter structures for the taxonomy of chronic pain and their rationales will be reviewed.

Historically, pain conditions have been most indelibly associated with anatomic structures, thus hewing closely to chief complaints. An anatomically based pain taxonomy, with entities such as headache, low back pain, and pelvic pain, is readily understood by nonspecialist providers and people experiencing pain, and is in some sense canonized by virtue of inclusion in the International Classification of Disease coding system. Nonetheless each anatomic region includes several tissue types that can act as pain generators and several individual conditions with different postulated pathophysiological mechanisms.

A recent review illustrates this point with the example of chronic low back pain.⁴ The low back is a complex region composed of several tissue types, including bone, ligament, joints, disc, muscle, and neural elements including nerve terminals in multiple innervated structures, nerve roots, and sensory ganglia. The authors summarize the large body of experimental evidence of numerous pain mechanisms within and beyond these structures, including structural pathology that activates nociceptors innervating musculoskeletal elements, release of inflammatory cytokines in response to structural pathology, compression and subsequent dysfunction of neural elements in contact with structural pathology, and upstream modulation and modification of somatosensory structures. Furthermore, insofar as pain is a symptom, the perception and report of pain can reflect a wide range of internal, interpersonal, and societal factors. Put simply, pain as a symptom can be a surrogate for distress, anxiety, and fear relating to its significance to the individual as a potential predictive biomarker of morbidity, mortality, or loss of life roles. Seen in these ways, it is clear that a taxonomy of pain based upon anatomic structures alone is a necessary but insufficient approach to understanding chronic pain.

As indicated, in some contexts tissue types have come to represent pain categories. These include such things as musculoskeletal, vascular, and neuropathic pain. Even cancer pain may be conceptualized within this framework, insofar as rapidly growing clonal tissues may activate nociceptive pathways via common mechanisms. Like a taxonomy based upon anatomic structures, this approach has the appeal of providing categories that are recognizable to patients and clinicians. Unlike categorization based upon anatomic structures alone, however, a taxonomy based upon tissue types implies the existence of pain mechanisms unique to these tissues.

The following are examples of pain categories based upon anatomic structures and tissue types that will be familiar to most readers:

Musculoskeletal Pain

Musculoskeletal pain is presumably generated in joints or in the ligaments and tendons that link the contractile apparatus (muscle) to joints. Joint pain may reflect medical diagnoses of either degenerative or inflammatory disorders; with respect to pain mechanism, however, both physiological activation of nociceptors from structural pathology and nociceptor sensitization from inflammation may apply in both settings. Musculoskeletal pain can also be caused by impingement or overuse syndromes.

Myofascial Pain

Myofascial pain is characterized by spontaneous and stimulus-evoked pain in soft tissues or over muscle, sometimes referred to as “trigger points.” Mechanistic hypotheses suggest that this may reflect either local phenomena or dysfunctional sensory modulation in the central nervous system, which will be discussed in greater depth.⁵

Spinal Pain

As noted earlier, spinal pain shares some features of musculoskeletal pain but is often considered a unique category because of its high prevalence and the variable presumed contributions from musculoskeletal, neuropathic, and in some cases myofascial elements.

Headache

Headache has a wide variety of etiologies and an established taxonomy distinct from other anatomic pain locations.⁶

Visceral and Pelvic Pain

Visceral pain is triggered by visceral distention and has a distinct character and differential diagnosis. Pelvic pain has a broad differential diagnosis as well, with specific conditions reflecting disorders of the reproductive organs, as well as neuropathic, musculoskeletal, and other organ-specific conditions.

Vascular Pain

Vascular pain syndromes presumably share an ischemic etiology and include claudication, rest pain due to severe limb ischemia, Reynaud’s disease (an isolated phenomenon), and Reynaud’s syndrome (Reynaud’s symptoms in the context of systemic inflammatory disease).

Neuropathic Pain

Neuropathic pain is arguably distinct from pain in other tissue types, in that it is “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.”⁷, rather than physiological nociceptive reporting of tissue injury outside of the nervous system. Neuropathic pain has several distinct phenomenological characteristics and includes a range of well-defined disorders of the peripheral and central nervous system.

Cancer Pain

Most pain taxonomies include cancer pain as a distinct entity because of its prevalence and its unique clinical circumstance and management strategies. In fact, cancer is associated with several distinct pain conditions that are not mutually exclusive, including bone pain from metastases, local pain from mass lesions, pain from complications of surgery and radiation therapy, and neuropathic pain from chemotherapy.

Landmark investigations in the late twentieth century^8–10 and an exponential increase in research more recently have elucidated chronic pain mechanisms that extend our knowledge of this field well beyond the model of nociceptive signal transduction and transmission in normal physiological circumstances. These modify nociceptive signaling in ways that are both physiological, in the sense that they represent inherent responses of normal cells after tissue injury, and pathological, in the sense that they contribute to adverse clinical outcomes without evident benefit to the organism.

Acute pain in response to tissue injury is, of course, a physiological phenomenon that is adaptive, in that it not only provides information that localizes and characterizes the injury but also triggers withdrawal and protective responses. In addition it is often associated with local, readily reversible modulation of nociceptor sensitivity (peripheral sensitization) and allodynia that are triggered by inherent neural mechanisms as well as inflammatory modulators released at the site of injury. These, too, can be considered physiological and adaptive, insofar as they promote guarding of the now injured and healing tissue.

It is now established that peripheral sensitization can persist well beyond the period of healing (e.g., postherpetic neuralgia) and thereby become maladaptive.¹¹ Furthermore, modulation and modifications of somatosensory pathways in the central nervous system (central sensitization) can contribute to stimulus-evoked or spontaneous pain, either after injury to the central nervous system or for currently unknown reasons. Central sensitization can be caused by injury in neural pathways and by glial activation.¹² In addition to sensitization, alterations in physiological mechanisms of pain modulation from brainstem structures and disinhibition of afferent pathways can exacerbate the perception of pain.

These mechanisms of pain amplification and maintenance in chronic pain states are associated not only with physiological changes but also with structural modifications. These include changes in nociceptor receptor density,¹³ synaptic structure in the dorsal horn,¹⁴ and gray matter density in the brain.¹⁵ Furthermore, while it is inherently plausible that such pain mechanisms could result in neuropathic pain states as a response to injury or disease in the nervous system, some of these same mechanisms have been implicated in other conditions historically classified with other anatomic sites or organ systems. In particular, there is some experimental evidence that fibromyalgia and irritable bowel syndrome may be associated with altered pain modulation in the central nervous system as a cause or contributant.^16–19

It is now clear that the localization of pain to a particular anatomic location is only the first step in understanding the generators of pain as a symptom. A wide variety of tissue types and pain mechanisms, in the categories of both physiological nociception and dysfunctional alterations in nociceptive mechanisms, can contribute to a pain complaint. Furthermore an individual clinical problem can reflect a complex spectrum of factors extrinsic to the narrowly defined pain mechanisms, including developmental, personality, interpersonal, cultural, and societal factors, that cannot be identified or treated by addressing physiological factors alone.