Receptors & Pathways

The sense organs for pain are the naked nerve endings found in almost every tissue of the body. Pain impulses are transmitted to the CNS by two fiber systems. One nociceptor system is made up of small myelinated Aδ fibers 2-5 um in diameter, which conduct at rates of 12-30 m/s. The other consists of unmyelinated C fibers 0.4-1.2 um in diameter. These latter fibers are found in the lateral division of the dorsal roots and are often called dorsal root C fibers. They conduct at the low rate of 0.5-2 m/s. Both fiber groups end in the dorsal horn; Aδ fibers terminate primarily on neurons in laminas I and V, whereas the dorsal root C fibers terminate on neurons in laminas I and II. The synaptic transmitter secreted by primary afferent fibers subserving fast mild pain (see below) is glutamate, and the transmitter subserving slow severe pain is substance P.

The synaptic junctions between the peripheral nociceptor fibers and the dorsal horn cells in the spinal cord are the sites of considerable plasticity. For this reason, the dorsal horn has been called a gate, where pain impulses can be "gated," ie, modified.

Some of the axons of the dorsal horn neurons end in the spinal cord and brain stem. Others enter the anterolateral system, including the lateral spinothalamic tract. A few ascend in the posterolateral portion of the cord. Some of the ascending fibers project to the ventral posterior nuclei, which are the specific sensory relay nuclei of the thalamus, and from there to the cerebral cortex. PET and fMRI studies in normal humans indicate that pain activates cortical areas SI, SII, and the cingulate gyrus on the side opposite the stimulus. In addition, the mediofrontal cortex, the insular cortex, and the cerebellum are activated.

Pain was called by Sherrington "the physical adjunct of an imperative protective reflex." Painful stimuli generally initiate potent withdrawal and avoidance responses. Furthermore, pain is unique among the sensations in that it has a "built-in" unpleasant affect.