Pain is a subjective feeling, an unpleasant sensation in a certain region of the body that represents an important defensive mechanism of the human body, a mechanism informing it about potentially damaging stimuli. Pain may seem a nuisance; however, patients who lack this sense are in constant danger of not noticing stimuli that may induce a major injury (for example, a very hot iron, a burner, or a chemical that can damage skin).
The sense of pain has its own system of peripheral receptors (nociceptors) and central neural structures. Nociceptors are scattered all over the body, both in the skin and in deep tissues. They are small sensory endings that generate action potential in response to a potentially damaging stimulus of a certain modality, such as temperature, pressure, or certain chemicals. These signals are transmitted along thin fibers of the A-delta and C-types. The speed of transmission along A-delta fibers ranges from 5 to 30 m/s, while C-fibers transmit impulses at speeds ranging from 0.5 to 2 m/s (see chapter 3). Activation of A-delta fibers by thermal or mechanical stimuli leads to sharp, pricking pain. Activation of C-fibers is associated with long-lasting, burning pain.
The sensitivity of nociceptors may be increased by damage of peripheral tissues or by inflammation (hyperalgesia), which may decrease the threshold of stimuli perceived as painful or increase the magnitude of pain without a change in the threshold.
Pain can emerge, however, in the absence of nociceptor activity. Typical examples involve pain accompanying damage of a peripheral nerve or phantom pain occurring after amputation of a limb. The worst possible scenario is chronic pain, which may be felt in an area of the body even after a total transection of the spinal cord does not allow signals from this area to reach the brain. The origins of chronic pain are not clear, and its therapy is commonly unsuccessful. One hypothesis is that the subjective feeling of pain is created by a disparity between signals from proprioceptors and signals from nociceptors (figure 26.11). This hypothesis is called the gate control theory of pain (Melzack and Wall 1965; Wall 1978). This theory predicts that a decrease in the activity of proprioceptors may be a strong enough factor to induce a feeling of chronic pain without any additional contribution from nociceptors. For example, during ischemia (blocked blood flow into a limb), the first fibers to stop transmitting impulses are the fastest conducting ones. These involve, in particular, Ia and Ib afferents from muscle spindles and Golgi tendon organs and also Aa-fibers from large cutaneous receptors. If the blood flow in a person’s arm is blocked, after a few minutes the person will report a burning pain in the arm, which will subside after some time. When the blood flow is restored, the pain returns again and disappears after a few minutes. Probably, everyone has experienced a similar feeling when a limb falls asleep after a prolonged stay in an uncomfortable posture and then wakes up. These observations may be explained by the ordered blockade and restoration of conduction along afferent fibers of different sizes.
- Use the idea that pain equals signals in nociceptors minus signals in proprioceptors to suggest a method of treating chronic pain.
The afferent fibers of nociceptors enter the spinal cord through the dorsal roots and make synaptic connections with interneurons in laminae I through V. They also send branches in the Lissauer tract that make synaptic connections a few segments rostrally and a few segments caudally to the dorsal root entrance. This mixture of information across several segments may underlie, in particular, the phenomenon of pain irradiation, which occurs when pain spreads beyond the apparent limits of the nociceptive stimulus.
Nociceptive information is transmitted to the brain structures along five major ascending pathways. These are the spinothalamic tract, the spinoreticular tract, the spinomesencephalic tract (going to the mesencephalic reticular formation), the spinocervical tract terminating in the lateral cervical nucleus, and the tract that runs in the dorsal column of the spinal cord to the cuneate and gracile nuclei of the medulla. The spinothalamic tract has been the most extensively studied. The thalamus apparently relays the nociceptive information to the cerebral cortex; however, it is not clear how the cortex processes these signals. In particular, patients with extensive cortical lesions of the somatosensory areas do not lose the ability to perceive pain.
Pain can be controlled by central mechanisms. In particular, electrically stimulating certain brain areas, including the ventrobasal region of the thalamus and the internal capsule, can produce analgesia without affecting the senses of touch and temperature. The descending pathway mediating analgesia has been shown to involve medullar structures, such as the nucleus raphe magnus, the nucleus paragigantocellularis, and the dorsolateral funiculus. Increasing the activity along this pathway suppresses the activity of dorsal horn neurons that respond to noxious stimuli. Similar effects can be produced by opiates (for example, morphine) and are likely to be mediated by the same mechanism. Opioid and nonopioid mechanisms are probably involved in analgesia induced by stress, which is well known from anecdotal reports by athletes, soldiers, and explorers.