Understanding chronic pain

Nursing, Apr 2004 by Yezierski, Robert P, Radson, Ellyn, Vanderah, Todd W

QUESTION: What causes chronic pain, and why do some drugs work better than others for managing it?

ANSWER: Unlike acute pain, which warns of actual or potential tissue damage, chronic pain serves no useful purpose. Pain scientists still aren't sure why chronic pain develops, but they do know that the longer pain stimuli act on the central nervous system (CNS), the more likely chronic pain is to develop.

Early recognition and treatment of a patient's acute pain helps prevent sensitization of the CNS, which can lead to chronic pain. But if your patient is already experiencing chronic pain, focus your assessment and treatment on possible underlying causes of pain and symptom management. Research indicates that chronic pain is best treated using a multidisciplinary approach.

To understand why and how certain drugs work for chronic pain, let's look at central sensitization, the mechanism by which acute pain turns chronic.

Getting nervy

When peripheral tissue is injured or inflamed, the intense, repeated, or prolonged stimuli lead to sensitization-a lowering of the threshold required to activate peripheral nerve fibers (see Mechanisms of Sensitization). Once tissue is sensitized, even harmless stimuli can trigger pain sensations.

Drugs such as nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase and block prostaglandins, disrupting the inflammatory process. Local anesthetics block pain sensation by disrupting the transmission of pain signals in peripheral nerve fibers.

Other drugs that ease chronic pain work by interrupting pain transmission at the dorsal root ganglia, where peripheral nerves originate. Peripheral nerve fibers enter the spinal cord as primary afferent projections and connect with secondary neurons. These fibers contain various transmitter substances, including the excitatory amino acid (EAA) glutamate, and neuropeptides such as substance P, which activate pain transmission neurons in the spinal cord. The release of EAA activates a family of specialized glutamate receptors that regulate the flow of calcium, sodium, potassium, and chloride ions across cell membranes. Anticonvulsants such as carbamazepine block sodium channels; gabapentin is thought to block calcium channels. Ketamine and dextromethorphan block other chemical receptors.

If acute peripheral pain continues untreated, glutamate receptors and a complex intracellular signaling cascade change how neurons in the spinal cord function, leading to a state of heightened excitability in the CNS, called central sensitization. In the spinal cord, this means:

* a significant reduction in the threshold required to activate pain transmission neurons

* a heightened response to pain stimuli

* an increase in the spontaneous discharge of pain transmission neurons.

Neurons in the brain also undergo functional changes if acute pain isn't treated: The repeated activation lowers their activation threshold too.

One reason for the shortage of acceptable long-term treatments for chronic pain is that current medications fail to effectively target the cellular mechanisms responsible for these functional changes.

What goes up must come down

The ascending pain pathway from peripheral nerves to the spinal cord and brain is paralleled by a descending pain pathway. Originating in the brain stem, this descending pathway inhibits pain transmission neurons via compounds such as enkephalin and serotonin. Many drugs that effectively treat chronic pain, such as opioids and antidepressants, mimic the action of the inhibitory transmitter system associated with the descending pathway.

Because pain has an affective component, chronic pain can cause anxiety, anger, and depression.

Many nonpharmacologic approaches to chronic pain management (such as psychological counseling, support groups, exercise, massage, and physical therapy) are directed toward decreasing the patient's emotional response to pain or helping him develop skills to cope with stress and other changes that impair his quality of life.

These alternative and complementary approaches can be an important component of an effective pain management program.

SELECTED REFERENCES

Craig, A.: "Neural Basis of Pain and Analgesia," in Encyclopedia of Cognitive Science, L. Nadel (ed). London, England. Nature Publishing Group, 2003.

Price, D.: "Psychological and Neural Mechanisms of the Affective Dimension of Pain," Science. 288(5472):1769-1772, June 9, 2000.

BY ROBERT P. YEZIERSKI, PHD; ELLYN RADSON, RN, BSN; AND TODD W. VANDERAH. PHD

Robert P. Yezierski is director of the Comprehensive Center for Pain Research at the University of Florida in Gainesville. Ellyn Radson is a clinical research nurse in the department of anesthesiology at the University of Florida. Todd W. Vanderah is an assistant professor of pharmacology and anesthesiology in the department of pharmacology at the University of Arizona in Tucson.