Pain Pathophysiology and Management

Definition and Epidemiology

According to the International Association for the Study of Pain (IASP), pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage.” Chronic pain is defined as “persistent or recurrent pain lasting longer than 3 months.” Per the current version of the International Classification of Diseases (ICD) of the World Health Organization (WHO), “Chronic Pain” is divided into 7 clinical pain syndromes: (1) chronic primary pain, (2) chronic cancer pain, (3) chronic posttraumatic and postsurgical pain, (4) chronic neuropathic pain, (5) chronic headache and orofacial pain, (6) chronic visceral pain, and (7) chronic musculoskeletal pain.

In the United States, chronic pain is estimated to affect about 20%–30% of the adult population, accounting for more patients than diabetes, heart disease, and cancer combined. Not surprisingly, pain is the most common reason Americans access the health care system, the most common cause of long-term disability, and a tremendous socioeconomic burden. The US healthcare cost associated with pain is estimated in the range of $300 billion, with another approximately $300 billion resulting from lost productivity at work. The most common pain conditions are chronic low back pain, neck pain, and headaches, followed by large joint pain (hip, knee, shoulder); at least 50% of all cancer patients name pain as one of the major symptoms of their disease. Except for headache, the prevalence of most chronic pain conditions increases with age often due to progression of osteoarthritis.

Pain Classification

Nociceptive pain due to activation of nociceptors from actual or threatened damage of nonneuronal tissue can be distinguished from neuropathic pain, which is a result of direct damage to the peripheral or central nervous system. Nociceptive pain arises in either the somatosensory or viscerosensory afferents from mechanical damage or by tissue inflammation. Neuropathic pain in contrast is caused by intrinsic damage to the sensory components of the nervous system, either in the peripheral (nerve, nerve root, nerve plexus) or central nervous system (spinal cord and brain). Clinical examples for nociceptive/inflammatory pain include any kind of trauma, postsurgical pain, osteoarthritis, rheumatologic disease, visceral inflammatory disease, and infection-related pain. Examples of peripheral neuropathic pain include mechanical nerve/nerve root damage; toxic-metabolic nerve injury as seen in diabetic, alcoholic, nutrition-deficiency neuropathies; nerve entrapments; and demyelinating peripheral disease like chronic inflammatory demyelinating polyneuropathy (CIDP). Central neuropathic pain is caused by damage to the nerve root entry zone, the spinothalamic tract, or the sensory thalamus by any process. For development of central neuropathic pain, the underlying pathology of the central lesion is less important than the location in the nociceptive system. Common conditions include ischemic and hemorrhagic stroke, brain or spinal cord tumor, or trauma, spinal syringomyelia, and demyelination due to multiple sclerosis.

Pain Function

The ability to sense pain evolved from the most primitive of nervous systems and has been preserved throughout evolution to avoid actual or impeding tissue damage and to increase survival. The congenital inability to sense pain due to gene mutations of a voltage-gated sodium channel (Na _v 1.7) results in early mutilations, trauma, and sometimes early death. This type of pain, indicating an acute threat to tissue integrity, is termed nociceptive pain, and it requires a high-intensity stimulus to activate pain-sensing fibers. Once tissue damage has occurred, inflammatory mediators released by the damaged tissue and the immune system result in hypersensitivity of the injured area, discouraging further physical contact and promoting the healing process. This inflammatory pain, mediated by a lowered activation threshold of pain-sensing structures, is triggered by mild- to moderate-intensity stimuli and persists until inflammation has resolved. In contrast to nociceptive and inflammatory pain, pathological pain is a chronic pain condition which does not serve any protective purpose, but rather represents a maladaptive state of the nociceptive system and a disease in its own right. This can be due to detectable injury to the peripheral or central nervous system (neuropathic pain) or changes in pain processing and perception (centralized or dysfunction pain disorder).