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Harrison’s Manual of Medicine



Organization of Pain Pathways
Chronic Pain

Pain is the most common symptom of disease. Management depends on determining its cause and alleviating triggering and potentiating factors.
Organization of Pain Pathways
(See HPIM-15, Fig. 12-1.) Pain-producing (nociceptive) sensory stimuli in skin and viscera activate peripheral nerve endings of primary afferent neurons, which synapse on second-order neurons in cord or medulla. These second-order neurons form crossed ascending pathways that reach the thalamus and are projected to somatosensory cortex. Parallel ascending neurons connect with brainstem nuclei and ventrocaudal and medial thalamic nuclei. These parallel pathways project to the limbic system and underlie the emotional aspect of pain. Pain transmission is regulated at the dorsal horn level by descending bulbospinal pathways that contain serotonin, norepinephrine, and several neuropeptides.
Agents that modify pain perception may act to reduce tissue inflammation (glucocorticoids, NSAIDs, prostaglandin synthesis inhibitors), to interfere with pain transmission (narcotics), or to enhance descending modulation (narcotics and antidepressants). Anticonvulsants (gabapentin, carbamazepine) may be effective for aberrant pain sensations arising from peripheral nerve injury.
Pain may be of somatic (skin, joints, muscles), visceral, or neuropathic (injury to nerves, spinal cord pathways, or thalamus) origin. Characteristics of each are summarized in Table 1-1.

Table 1-1 Characteristics of Somatic and Neuropathic Pain

Sensory symptoms and signs in neuropathic pain are described by the following definitions: neuralgia: pain in the distribution of a single nerve, as in trigeminal neuralgia; dysesthesia: spontaneous, unpleasant, abnormal sensations; hyperalgesia and hyperesthesia: exaggerated responses to nociceptive or touch stimulus, respectively; allodynia: perception of light mechanical stimuli as painful, as when vibration evokes painful sensation. Reduced pain perception is called hypalgesia or, when absent, analgesia. Causalgia is continuous severe burning pain with indistinct boundaries and accompanying sympathetic nervous system dysfunction (sweating; vascular, skin, and hair changes—sympathetic dystrophy) that occurs after injury to a peripheral nerve.

Acute Somatic Pain If moderate, it can usually be treated effectively with nonnarcotic analgesic agents (Table 1-2). For subacute musculoskeletal pain and arthritis, selective Cox-2 inhibitors such as rofecoxib or celecoxib are useful, especially if the pt is at risk for upper gastrointestinal ulceration or bleeding. Narcotic analgesics are usually required for relief of severe pain; the dose should be titrated to produce effective analgesia.

Table 1-2 Drugs for Relief of Pain

Neuropathic Pain Often chronic; management is particularly difficult. Most pts are treated optimally with a combination of the anticonvulsant gabapentin and an antidepressant such as nortriptyline.

Chronic Pain
The problem is often difficult to diagnose, and pts may appear emotionally distraught. Psychological evaluation and behaviorally based treatment paradigms are frequently helpful, particularly in a multidisciplinary pain management center.
Several factors can cause, perpetuate, or exacerbate chronic pain: (1) painful disease for which there is no cure (e.g., arthritis, cancer, migraine headaches, diabetic neuropathy); (2) neural factors initiated by a bodily disease that persist after the disease has resolved (e.g., damaged sensory or sympathetic nerves); (3) psychological conditions.
Pay special attention to the medical history and to depression. Major depression is common, treatable, and potentially fatal (suicide).

After evaluation, an explicit treatment plan should be developed, including specific and realistic goals for therapy, e.g., getting a good night’s sleep, being able to go shopping, or returning to work. A multidisciplinary approach that utilizes medications, counseling, physical therapy, nerve blocks, and even surgery may be required to improve the pt’s quality of life. Some pts may require referral to a pain clinic; for others, pharmacologic management alone can provide significant help. The tricyclic antidepressants are useful in management of chronic pain from many causes, including headache, diabetic neuropathy, postherpetic neuralgia, atypical facial pain, and chronic low back pain. Anticonvulsants benefit pts with chronic neuropathic pain and little or no evidence of sympathetic dysfunction (e.g., diabetic neuropathy, trigeminal neuralgia).


For a more detailed discussion, see Fields HL, Martin JB: Pain: Pathophysiology and Management, Chap. 12, p. 55, in HPIM-15.



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