The pain produced by injuries of similar magnitude is remarkably variable in different situations and in different individuals. For example, athletes have been known to sustain serious fractures with only minor pain, and Beecher’s classic World War II survey revealed that many soldiers in battle were unbothered by injuries that would have produced agonizing pain in civilian patients. Furthermore, even the suggestion of relief can have a significant analgesic effect (placebo). On the other hand, many patients find even minor injuries (such as venipuncture) frightening and unbearable, and the expectation of pain has been demonstrated to induce pain without a noxious stimulus. The powerful effect of expectation and other psychological variables on the perceived intensity of pain implies the existence of brain circuits that can modulate the activity of the pain-transmission pathways. One of these circuits has links in the hypothalamus, midbrain, and medulla, and it selectively controls spinal pain-transmission neurons through a descending pathway (Fig. 1-4).
Human brain imaging studies have implicated this pain-modulating circuit in the pain-relieving effect of attention, suggestion, and opioid analgesic medications. Furthermore, each of the component structures of the pathway contains opioid receptors and is sensitive to the direct application of opioid drugs. In animals, lesions of the system reduce the analgesic effect of systemically administered opioids such as morphine.
FIGURE 1-4 Pain transmission and modulatory pathways.
A. Transmission system for nociceptive messages. Noxious stimuli activate the sensitive peripheral ending of the primary afferent nociceptor by the process of transduction. The message is then transmitted over the peripheral nerve to the spinal cord, where it synapses with cells of origin of the major ascending pain pathway, the spinothalamic tract. The message is relayed in the thalamus to the anterior cingulate (C), frontal insular (F), and somatosensory cortex (SS).
B. Pain-modulation network. Inputs from frontal cortex and hypothalamus activate cells in the midbrain that control spinal pain-transmission cells via cells in the medulla.
Along with the opioid receptor, the component nuclei of this pain-modulating circuit contain endogenous opioid peptides such as the enkephalins and b-endorphin. The most reliable way to activate this endogenous opioid-mediated modulating system is by prolonged pain and/or fear.
Since pain-transmission neurons can be activated by modulatory neurons, it is theoretically possible to generate a pain signal with no peripheral noxious stimulus. In fact, human functional imaging studies have demonstrated increased activity in this circuit during migraine headache. A central circuit that facilitates pain could account for the finding that pain can be induced by suggestion or enhanced by expectation, and it could provide a framework for understanding how psychological factors can contribute to chronic pain.
There is evidence that pain-relieving endogenous opioids are released following surgical procedures and in patients given a placebo for pain relief. Pain-modulating circuits can enhance as well as suppress pain. Both pain-inhibiting and pain-facilitating neurons in the medulla project to and control spinal pain-transmission neurons.