American College of Physicians: Internal Medicine — Doctors for Adults ®


The anatomy of pain

From the December ACP Observer, copyright 2004 by the American College of Physicians.

The afferent nociceptive system originates peripherally with pain receptors, or nociceptors, the freely branching termini of pain fibers. Unlike fibers that carry benign stimuli, these fibers discharge with increasing intensity as the stimulus becomes stronger. Nociceptors respond to heat, chemicals and pressure.

The dorsal root ganglion houses the nerve cell bodies of pain neurons. Each neuron gives rise to an axon and a dendrite, with one coursing peripherally and the other centrally to enter the dorsal root of the spinal cord. Upon entering the spinal cord, the axons of primary neurons synapse on secondary neurons in the ipsilateral dorsal horn.

Second-order neurons may give rise to long axons that cross the midline and form ascending spinal tracts. (Alternatively, second-order neurons may function as interneurons, modulating activity within the dorsal horn.) The ascending tracts have been subdivided into those that carry "fast pain" impulses—the neospinothalamic tracts—and those that carry "slow pain" impulses, or the paleospinothalamic tracts.

Experts believe that the neospinothalamic tracts are phylogenetically more recent. They convey precise localizing information about pain stimuli and terminate on neurons in the thalamus, which project to the sensory cortex. In contrast, the paleospinothalamic tracts terminate on the phylogenetically older portions of the brain, which include the brain stem and limbic system. These tracts are believed to be important in creating the affective dimension of the pain experience.

Nervous system mechanisms help modulate the intensity of pain stimuli. Serotonergic and noradrenergic tracts descend from the brain stem to the dorsal horn, where they influence the processing of nociceptive input from the primary afferent fibers. This modulatory system is a useful therapeutic target in the management of chronic pain.

Endogenous opioids are a second important modulatory system. Opioid receptors are expressed ubiquitously throughout the central and peripheral nervous systems, and form a critical pharmacologic target.

Pathophysiology of pain

As we have broadened our understanding of pain pathophysiology, three mechanisms have emerged as viable therapeutic targets. They include: 1) sensitization of peripheral nociceptors; 2) ectopic nociceptive activity; and 3) central hypersensitization.

  • Sensitization of peripheral nociceptors by a variety of agents can cause them to fire more readily and with greater intensity. Prostaglandins, whose synthesis is inhibited by nonsteroidal anti-inflammatory drugs, are prototypic sensitizing agents.

  • Ectopic activity has been recorded in neurons following injury in both animal models and patients with chronic pain. Experts believe that the over-expression, increased density and aberrant processing of sodium channels are responsible for this phenomenon.

  • Central hypersensitization involves plasticity of the central nervous system. When an intense and constant barrage of nociceptive stimuli enters the dorsal horn, it alters the behavior of the secondary nociceptive neurons to widen receptive fields, reduce discharge thresholds and prolong afterdischarges.

This phenomenon, known as "wind up," is mediated predominantly through the activity of the N-methyl D-aspartase receptor.


Additional pain management resources


Annals of Internal Medicine:

"Pain: Moving from Symptom Control Toward Mechanism-Specific Pharmocologic Management." Annals of Internal Medicine. 2004: 140; 441-451. PMID: 15023710.

"Palliative Treatments of Last Resort: Choosing the Least Harmful Alternative." Annals of Internal Medicine. 2000: 132; 488-493. PMID: 10733450.

"Pain Management in Patients with Advanced Cancer." Annals of Internal Medicine. 2000: 132; 593. PMID: 10744602.

Other journals:

"Comparative Efficacy and Safety of Long-Acting Oral Opioids for Chronic Non-Cancer Pain: A Systematic Review." Journal of Pain and Symptom Management. 2003: 26;1026-48. PMID: 14585554.

"Depression and Pain Comorbidity: A Literature Review." Archives of Internal Medicine. 2003: 163; 2433-45. PMID: 14609780.

"A Randomized Trial of Combined Manipulation, Stabilizing Exercises, and Physician Consultation Compared to Physician Consultation Alone for Chronic Low Back Pain." Spine. 2003: 28; 2185-91. PMID: 14520029.

"Pain Assessment in Cognitively Impaired and Unimpaired Older Adults: A Comparison of Four Scales." Pain. 2001: 92; 173-86. PMID: 11323138.

"Pain Management in Frail, Community-Living Elderly Patients." Archives of Internal Medicine. 2001:161; 2721-4. PMID: 11732938.

"Trends in Medical Use and Abuse of Opioid Analgesics." Journal of the American Medical Association. 2000: 283; 1710-4. PMID: 10755497.

Professional societies

Additional Resources

  • Federation of State Medical Boards. "Model Policy for the Use of Controlled Substances for the Treatment of Pain"

  • Medline Plus. A patient information service of the National Library of Medicine and the National Institutes of Health.

  • National Guideline Clearinghouse. Pain Management Guidelines

  • PIER (Physicians' Information and Education Resource). Pain

  • University of Wisconsin Pain and Policy Studies Group (PPSG). Information about pain relief and public policy, including material published by the PPSG and other authoritative sources. Different state policies on pain management, including documentation requirements.


Annual Session 2005 courses

The following courses related to pain management will be offered at ACP's Annual Session 2005, April 14-16, 2005, in San Francisco:

  • Challenges in Pain Management for Patients Near End of Life, Janet L. Abrahm, FACP, Dana-Farber Cancer Institute, Boston.

    Thursday, April 14, 4-5:30 p.m.

  • Back Pain and Radiculopathy: What the Internist Should Know, David G. Borenstein, FACP, Washington.

    Friday, April 15, 1:45-3:15 p.m.
    Saturday, April 16, 6:45-8:15 a.m.

  • Drug, Alcohol and Other Addictions, Patrick G. O'Connor, ACP Member, Yale University School of Medicine.

    Saturday, April 16, 8:30-10 a.m.

  • Narcotic Analgesics in General Medical Practice: Rational Choices and Proper Uses, Scott Fishman, MD; University of California, Davis Medical Center.

    Saturday, April 16, 10:45 a.m.-12:15 p.m.

Register online for Annual Session 2005, or call 800-523-1546, ext. 2600 (M-F, 9 a.m.-5 p.m., ET).


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