PAIN PATHWAYS

Although we talk of a "pain pathway", it is more accurate to think in terms of a complex and constantly changing system. The neurological pathways involved send signals to the cortex where they may be interpreted as pain.

Pathway Method of pain control Cortex General anesthetic Thalamus Opioids Spino-thalamic tracts Cordotomy Dorsal horn of spinal cord Opioids Sensory (nerve) fiber Local anesthetic Nerve endings Prostaglandin inhibitor

Nerve endings are sensitive to prostaglandins (and other chemicals) released by tissue damage such as bone metastases. Most tissues of the body give rise to pain when appropriately stimulated. (The exceptions are liver, lung, spleen and some regions of the brain.)

Sensory nerves are not specific for pain. For example, visceral sensory nerves that signal bladder or rectum distention, with increased activity will signal pain.

Sensory nerves from the internal organs run with the sympathetic nerves, as follows:

All sensory nerve fibers pass into the posterior nerve roots and then synapse (make contact) with cells in the dorsal horn of the spinal cord.

The dorsal horn of the spinal cord acts as a computer to collect and analyze sensory information. Cells in the dorsal horn send axons up the spino-thalamic tracts to the thalamus. The cells in the dorsal horn are connected by interneurons which regulate nerve activity.

Cells in the dorsal horn are strongly influenced by the activity in other dorsal horn cells in adjacent spinal segments (up or down). Thus pain in the hand due to median nerve compression can eventually spread up the arm. This is an example of hyperalgesia, when surrounding normal areas of the body can become sensitive or painful.

Chronic pain can produce permanent changes to the connections among the cells in the dorsal horn. Therefore, cutting a sensory nerve may not stop pain, because the (altered) pattern of nerve activity in the dorsal horn may continue to signal pain. For example, pain from an ischemic foot can continue even after the foot is amputated (phantom nerve pain).

There is considerable overlap. A single cell in the dorsal horn of the spinal cord may receive input from bladder, colon, skin and muscle. Input from skin and viscera can summate at the dorsal horn. Pain can thus be referred (for example, diaphragmatic irritation can cause pain in the shoulder).

Sensory nerves contain both touch fibers and pain fibers. Increased input from touch fibers can inhibit pain transmission. Touch fibers release encephalins in the dorsal horn, and if the touch stimulus is strong enough this can inhibit pain. (This effect is abolished by naloxone.) This is the basis of the "gate theory" of pain transmission, and the observation that rubbing the skin near a painful area can make it less painful. It also explains the effectiveness of TENS and high-frequency electro-acupuncture. It provides a theoretical model for future methods of analgesia.

Descending pathways descend from the midbrain to the cells of the dorsal horn of the spinal cord. They release encephalins. These descending pathways were discovered in 1969 by Reynolds (a psychologist working with rats). He found that minute quantities of morphine injected into a certain point of the midbrain of the rat could achieve whole-body analgesia, but the effect was lost by cutting descending pathways. These descending pathways inhibit pain transmission in the dorsal horn. They are activated by pain. Thus a severe pain in one part of the body can mask a less severe pain in another. Expectation of pain will activate these descending pathways in experimental animals. This provides an anatomical basis for the well-recognized effects of psycho-social factors on pain perception. Explanation, reassurance and psychological support can all reduce pain.

The spino-thalamic tracts convey fibers upwards from the cells of the dorsal horn of the spinal cord to the thalamus. They travel in the antero- lateral tracts of the spinal cord. A cordotomy (more correctly called an antero-lateral tractotomy) divides these fibers and renders parts of the body below the lesion analgesic. A bilateral cordotomy would render all parts of the body below the lesion analgesic. Some spino-thalamic fibers also pass to the midbrain (forming a feedback loop via the descending pathways) and to the hypothalamus (accounting for the autonomic response to severe pain of sweating and tachycardia).

The thalamus is an important part of the system of nerve pathways that can eventually signal pain. The cell fibers in the spino-thalamic tracts synapse with cells in the lateral thalamus. These cells are arranged somato-topically (each group of cells corresponds with an area of the body). However, some fibers pass to the medial thalamus, where each cell can receive input from a very large area of the body. The medial thalamus is concerned with the quality of pain. Electrical stimulation of the thalamus in conscious humans can cause burning pain in extensive areas of the body. Fibers from the thalamus pass to the cerebral cortex.

The cerebral cortex is the place where the pattern of nerve impulses is finally interpreted as pain. Hence the pathways are more correctly called nociceptive pathways (which may or may not cause the sensation of pain). The cerebral cortex also provides information about the location and intensity of pain.

The encephalins are small pepticles (discovered in 1975) which act on opioid receptors (particularly in the midbrain and the dorsal horn of the spinal cord). There are five main receptors now recognized. The encephalins act as the chemical messengers of a primitive inhibitory signaling system in the CNS. Morphine (a plant extract) happens to bind to the same receptors and is therefore an analgesic.

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