Mechanisms of cancer pain

Two major pain categories exist: nociceptive pain and neuropathic pain. Nociceptive pain results from tissue damage and can be further subdivided into somatic and visceral pain. Somatic pain may originate from multiple sites—including skin, muscle, joints, connective tissue, or bone—and is mediated by somatic afferent fibers (Aδ and C fibers). Somatic pain is most often described as sharp, throbbing, and well localized if it is superficial, or it is described as dull, aching, and less well localized if it is deep. Visceral pain originates from solid or hollow visceral organs and is mediated by visceral nociceptive afferent fibers that travel along with visceral sympathetic efferent fibers. Visceral pain is often described as a dull diffuse pain that is frequently referred in a dermatomal fashion.

Neuropathic pain occurs when there is damage to or dysfunction of nerves in the peripheral or central nervous system. The pain frequently has dysesthetic (e.g., burning, pricking) or paroxysmal (e.g., stabbing, shooting, electric shock-like) qualities and may be associated with sensory, motor, or autonomic dysfunction. Neuropathic pain may be centrally or peripherally generated. When the pain is coupled with loss of sensory input, it is referred to as deafferentation pain (e.g., phantom limb pain). When dysregulation of the autonomic nervous system plays a major role, the pain is referred to as sympathetically mediated pain (e.g., complex regional pain syndrome). Sympathetically mediated pain may occur after a nerve or limb injury; the patient often has diffuse burning pain of the affected extremity associated with allodynia, hyperpathia, sudomotor dysfunction, and signs of impaired blood flow regulation to the extremity. This pain is believed to be mediated, at least in part, by sympathetic efferent fibers. Deafferentation pain and sympathetically mediated pain are examples of centrally generated neuropathic pain. Examples of peripherally generated pain include polyneuropathies and mononeuropathies. Compared with nociceptive pain, neuropathic pain is often less responsive to conventional pharmacologic therapy.

One or more of these mechanisms may contribute to a patient’s pain and may occur as a result of the primary cancerous lesion, metastatic disease, neural compression, or treatments, such as radiation therapy, chemotherapy, or surgery. Pain may also originate from secondary nonmalignant sources (e.g., herniated nucleus pulposus, spinal stenosis, myofascial pain syndrome).

Medical therapy

The World Health Organization’s three-step analgesic ladder is a validated, clinical pain treatment algorithm that is very helpful in outlining a therapeutic pain management strategy for patients with cancer. The analgesic ladder progresses in a stepwise approach as pain increases and is utilized to meet individual needs. The approach begins with nonopioids; then, as necessary, it progresses to intermediate-potency opioids for moderate pain and then to more potent opioids for severe pain. Nonopioid medications and adjuvant medications may be used at each step depending on the type or types of pain being treated.

Adjuvant analgesic agents play a major role in treating patients with malignancies (Table 215-1). Most of these medications have a primary indication other than pain but have analgesic properties. The choice of adjuvant is made based on several assessments, including the type of pain, pharmacologic characteristics and adverse effects of the drug, interactions with other medications, and patient comorbid conditions (e.g., depression). Adjuvant agents comprise a diverse group of medications and can be broadly classified into multipurpose adjuvant analgesic agents and adjuvants specific for neuropathic pain, bone pain, musculoskeletal pain, and bowel obstruction.