Basic Anatomy and Physiology of Pain Pathways

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Key points

  • Pain signals are transmitted along Aδ and C nociceptive nerve fibers to the central nervous system.

  • Most peripheral nerve fibers will synapse in the Rexed lamina and then ascend in the contralateral spinothalamic tract before terminating in the ventral posterior nuclei and central nuclei of the thalamus.

  • The receptive fields of the thalamus may reorganize following injury.

  • The primary and secondary somatosensory cortex receive the bulk of direct projections from the thalamus; the insula,

Peripheral sensory system and mechanisms of sensitization

The location, intensity, and temporal pattern of noxious stimuli are transduced into a recognizable signal through unmyelinated nociceptors at the terminal end of sensory neurons. Through physical deformation or molecular binding, membrane permeability and, consequently, the membrane potential fluctuate.2 If depolarization reaches a critical threshold, an action potential is propagated along the length of a sensory nerve toward the spinal cord.

Most sensory receptors respond to a single stimulus

Dorsal root ganglia

Sensory neuron cell bodies are located in the dorsal root ganglia (DRG). DRG neurons are classically pseudounipolar; one process extends into the peripheral nerve and the other process extends centrally, transmitting information through the dorsal root into the spinal cord. Each DRG contains thousands of unique sensory neuron cell bodies that are capable of encoding and then transmitting specific information gathered from external stimuli.13 Cells in the DRG are subclassified into peptidergic

Spinal cord

Most sensory fibers project from the DRG through the dorsal root and into the dorsal root entry zone (DREZ). There is evidence that the ventral roots also receive projections from unmyelinated fibers originating from DRG cells that are involved in sensation, including nociception, violating the Bell-Magendie law.17, 18, 19, 20 At the DREZ, most unmyelinated and small myelinated axons project laterally to enter. Lissauer tract (see Fig. 1)21 fibers then extend vertically in this tract for

Spinothalamic pathways

The STT is oriented vertically along the ventrolateral portion of the spinal cord (see Fig. 1). It serves as the main conduit from the peripheral nerves to the brain by transmitting pain, temperature and deep touch signals to the thalamus. It receives projections from contralateral lamina I and IV-VI26 and is composed of two tracts: one dorsolateral, carrying axons from the superficial lamina, and the other ventrolateral, carrying axons from deeper lamina.27 Most projections are contralateral,

Thalamus

The sensory thalamus is divided into nuclei that roughly maintain the segmentation of the noxious and innocuous divisions from the periphery. The ventral caudal (Hassler's nomenclature) or ventroposterior (VP) nucleus thalamic nuclei are the most direct subcortical relay site for the STT and the trigeminal thalami ctract (TTT)27, 33 before relaying pain signals to the primary sensory cortex and other cortical regions.34 Glutaminergic projections from the dorsal column nuclei and from the DH via

Cortical areas

Painful stimuli activate distant cortical regions, including the primary somatosensory cortex (SI; Brodmann areas 3a/b, 2, 1, postcentral gyrus), secondary somatosensory cortex (SII), insula, orbitofrontal cortex, dorsal-lateral prefrontal cortex, extended amygdala, and cingulate cortex.27 The SI is arranged with somatotopic organization of nociceptive signals that follows Penfield's homuncular pattern.39 Projections from the VPM and VPL nuclei synapse directly in the SI. These neurons in SI

Descending systems

Descending pathways originating in the brain regulate incoming signals from noxious stimuli primarily through synapses on DH neurons (Fig. 3). Facilitative regulation amplifies the response as observed in sensitization. Alternatively, inhibitory regulation suppresses ascending pain signals during life-threatening events and other periods of extraordinary stress. These descending pathways include several relevant supraspinal structures: the rostral ventromedial medulla (RVM), the dorsolateral

Summary

Although the details underpinning the pain systems are debatable, the evolutionary advantage to having an integrative pain system culminating in the conscious recognition of pain is not. When studied using modern neuroimaging or electrophysiological studies, the nature of the perceptual experience of pain still remains fragmented. This has unfortunately delayed the development of novel neurosurgical approaches to treat chronic noncancer pain. Nevertheless, the surgical treatments represented in

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