What are the neuroanatomic pathways involved in pain?
Physiologic pain transmission begins with nociceptors, which are peripheral axons whose terminals transduce real or potential tissue injury. Cutaneous nociceptors, for example, are small myelinated or unmyelinated axons equipped with surface receptors that transduce real or potential skin injury into neuronal discharges, thus initiating a cascade of information to the brain regarding the nature, location, and severity of the threat. Cutaneous nociceptors are classified according to their fiber type (A-delta or C) and the type of tissue injury to which they respond; thus, for example, there are A-mechanical heat (AMH), a-mechanical (AM), C-mechanical, heat (CMH), C-mechanical, heat, chemical (CMHC), and so forth.
Nociceptors are present in numerous tissues, including skin, joints, connective tissue, and viscera, in order to signal a variety of external as well as internal threats to the organism. Afferent information is coded in nociceptive discharges; for example, the intensity of skin heating might be proportional to the firing rate of the axon. Nociceptive somatic primary afferent neurons synapse in the dorsal horn of the spinal cord with secondary afferent neurons that cross the spinal cord and form the corticospinal tract, which courses rostrally and forms synapses with thalamic cells. These in turn project to several cortical regions critical to the experience of pain.
Recall that pain is “an unpleasant sensory and emotional experience.” This definition reflects the nature of pain, which is to alert and motivate the organism to change its condition for the purpose of protection. Cortical projections in the physiology of pain reflect this as well. Projections to primary somatosensory cortex enable localization of pain, projections to limbic areas such as insular cortex and amygdala enable attribution of negative valence (unpleasantness), and projections to premotor frontal cortex enable a response to the inciting noxious stimulus, such as withdrawal and avoidance. Numerous other cortical regions are involved in pain projections as well. Thus the neuroanatomy of pain enables us to attend, localize, and react promptly in response to external threats.
In addition to these afferent pathways, descending modulation of pain plays a critical role in pain perception. Cells in the periacqueductal gray matter (PAG) and rostroventral medulla (RVM) project to the dorsal horn of the spinal cord, where they modulate the afferent signals from primary nociceptors. This descending modulation influences the intensity of the afferent signal from dorsal horn neurons. Physiologic influences on descending modulation can result in substantial differences in pain perception from identical peripheral nociceptive stimuli.
Finally, other pathways that interact with or synapse with cells in the primary somatosensory system can influence their response to nociceptive input. These include sympathetic efferents and activated glia, both of which can influence nociceptive traffic via their interactions with cells of the primary nociceptive pathway.