Pain afferents can be myelinated or unmyelinated.
An A-delta fiber responds to either mechanical stimuli or temperature stimuli in the painful realm and produces the acute sensation of sharp, bright pain. Their neurotransmitter in the dorsal horn is glutamate acting on AMPA receptors.
By contrast, a C fiber can respond to a broad range of painful stimuli, including mechanical, thermal or metabolic factors. The pain produced is slow, burning, and long lasting. The neurotranmitter in the dorsal horn is glutamate along with certain peptides such as substance P. The receptors for glutamate are not only AMPA, but also NMDA. Since the latter only open following prolonged depolarization, continual stimulation of C fibers eventually causes greater excitation in the postsynaptic neurons in the dorsal horn as the NMDA receptors start added to the response.
The receptor for capsaicin, which is found in hot peppers, is located in the C fibers. This ion channel normally is opened by hot stimuli.
The C fibers are interestingly interconnected with the process of inflammation. Observe the figure below. The directions that action potentials conduct should seem quite surprising, because action potentials in certain branches of an afferent neuron are moving peripherally!! The is called the axon reflex. The release of substance P there increases inflammation by causing histamine release and dilation of blood vessels.
One phenomenon you may have observed in yourself is that stimulation of touch sensors (A-beta fibers) in the skin by rubbing can disrupt the sensation of pain arising in a nearby structure such as a muscle. This is usually interpreted in terms of the gate control theory. Observe the figure of the dorsal horn, which shows that large, mechanically sensitive afferents excit interneurons that in turn inhibit the neurons that carry pain information from the dorsal horns to the brain. (Axons in the anterolateral tract project to the thalamus.)
What physiological function this might serve is not clear, but it does help explain various phenomena that reduce pain. The effect of transcutaneous electrical stimulation (TENS) presumably is due to this effect. In these devices, weak electrical current is applied to the skin near the site of pain (such as the lower back) in order to stimulate the A-beta fibers and reduce the flow of pain information to the brain.
Much more potent, however, is the analgesia producted by morphine and other related opiates. The opiates bind to opioid receptors found in many areas of the brain, but are especially concentrated in the periaqueductal gray(ie; the area surrounding the cerebral aqueduct in the midbrain), the medulla and the dorsal horns. Infusion of morphine into the periaqueductal gray is especially effective in producing profound analgesia. This also is the area of the brain in which electrical stimulation produces a strong analgesic effect.
Naturally, with such a potent effect, one suspects that the brain contains molecules that naturally activate the receptors that respond to the opiates. These molecules are termed the opioid peptides, and include the enkephalins, dynorphin and beta-endorphin. Beta-endorphin is released by neurons with cell bodies in the hypothalamus and we won't consider this further.
The enkephalins (and dynorphin) are found in the periaqueductal gray, the medulla and the dorsal horns. Observe the pathway to the left that descends from the periaqueductal gray via the medulla to the dorsal horns. This leads to the release from interneurons of enkephalins that inhibit the flow of pain information to the brain.
The term neuropathic pain refers to pain that arises due to altered neuronal properties rather than an actual painful stimulus. On the other hand, nocioceptive pain refers to pain that arises due to a painful stimulation of pain afferent neurons. A table on the handout under disorders compares the clinical presentation of the two. There is no need to memorize this table, but do become familiar with the terminology used.
Prolonged, chronic pain can also lead to conditions in which the sensation of pain is heightened. Clinicians refer to the increased sensation of pain with time as "wind-up".
One aspect of wind-up may be the steady release of substance P in the dorsal horns. Peptides are removed slowly and can diffuse around somewhat. The continued presence of substance P might lead to cellular changes such as increased neuronal sprouting. Other cellular changes might follow from activation of NMDA receptors. Recall that these only open with prolonged depolarization, such as would occur with prolonged pain. The resulting influx of Ca++ could activate enzymes (such as nitric oxide synthase) or trigger other long lasting cellular changes. In other words, prolonged pain seems to create a "memory" of itself.
Under neuropathic pain, we also discussed phantom limb pain , which occurs in amputees. Deafferentation pain is related.
Sympathetically maintained pain is a special type of chronic pain in which blocking the sympathetic nervous system helps relieve the pain.