Pain Pathways Medical Neuroscience | Tutorial

Pain Pathways

1 MAP TO NEUROSCIENCE CORE CONCEPTS

NCC1. The brain is the body's most complex organ. NCC3. Genetically determined circuits are the foundation of the nervous system. NCC7. The human brain endows us with a natural curiosity to understand how the world works. NCC8. Fundamental discoveries promote healthy living and treatment of disease.

LEARNING OBJECTIVES

After study of today’s learning, the student will: 1. Characterize the organization of the anterolateral system from peripheral nerve ending to cerebral cortex. 2. Recognize components of the anterolateral system in the spinal cord, brainstem, thalamus and cerebral cortex.2 3. Characterize the organization of the trigeminal pain & temperature (spinal trigeminal) system from peripheral nerve ending to cerebral cortex. 4. Recognize components of the trigeminal pain & temperature (spinal trigeminal) system in the brainstem, thalamus and cerebral cortex.1

TUTORIAL NARRATIVE

Introduction There are two major, parallel systems that convey somatic sensory information from the periphery of the post- cranial body to the cortex, the dorsal column-medial lemniscus system and the anterolateral system. There are comparable parallel systems carrying information from the face associated with the central projections of the trigeminal nerve. In addition, there is an important system carrying proprioceptive information from the muscle spindles to the cerebellum. This tutorial will focus on the pathways taken by the components of the systems for transmission of neural signals pertaining to pain and temperature sensation. It is important for your understanding of neurological deficits seen in the clinic to know where these pathways travel relative to each other and to other structures (including the cranial nerve nuclei) in the brain.

1 Visit BrainFacts.org for Neuroscience Core Concepts (©2012 Society for Neuroscience ) that offer fundamental principles about the brain and nervous system, the most complex living structure known in the universe. 2 As you study somatic sensory pathways, you should begin referring to cross sections through the nervous system (e.g., in Sylvius4) so that you can recognize where relevant nuclei and axonal tracts are located within the brain and spinal cord.

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Pathways mediating pain and temperature sensation.

The anterolateral system is responsible for conveying information about pain, temperature and crude touch (i.e., touch lacking the spatial resolution of the dorsal column system) from the post-cranial body. Comparable information about the face is processed in trigeminal pathways. These pathways are illustrated in Figures 1 and 2. Most peripheral processes associated with the dorsal root ganglion cells that contribute to this system are “free.” That is, they are not associated with encapsulated endings like those in the dorsal column-medial lemniscal system. In addition, the first-order fibers associated with the anterolateral system are generally much smaller in diameter than those associated with the dorsal column system. (So what does this tell you about the relative conduction velocities of these two important somatic sensory pathways?) The first-order neurons in the anterolateral system, like those in the dorsal column-medial lemniscal system, have their cell bodies in the dorsal root ganglia. The central processes of these neurons terminate on second- order neurons in the dorsal horn of the spinal cord. Pain and temperature information from receptors in the face is carried into the brain on the fifth nerve. The cell bodies of the first order neurons are in the trigeminal ganglion and the central processes of the cells make synapses in a nucleus in the medulla known as the spinal trigeminal nucleus (of the fifth nerve). This nucleus is actually continuous with the dorsal horn of the spinal cord. The second-order neurons in the dorsal horn of the spinal cord send their axons across the midline, where they accumulate in the anterolateral (ventrolateral) part of the white matter. They ascend in this location through the length of the cord. Many of these fibers continue through the medulla, the pons and the midbrain to contact third-order neurons in the ventral posterior lateral (VPL) nucleus of the thalamus (as well as other thalamic nuclei). This direct pathway from the spinal cord to the thalamus is often called the spinothalamic tract. Actually, the thalamus is only one of the targets of the second-order neurons in the anterolateral system. These neurons also project to central parts of the medulla, pons and midbrain known collectively as the reticular formation (this component of the anterolateral system is known as the “spinoreticular tract”) and to the periaqueductal gray matter and the superior colliculus (this component is known as the “spinomesencephalic tract”). Second-order neurons located in the spinal trigeminal nucleus send their axons across the midline to form the ventral trigeminothalamic tract, which travels to the ventral posterior medial (VPM) nucleus of the thalamus. Third-order neurons in the ventral posterior nucleus and in other thalamic nuclei then project to the cortex via the internal capsule. The postcentral gyrus appears to be important for the ability to discriminate the exact location of painful stimuli, but many other, less well-understood cortical areas (including areas in the anterior part of the cingulate gyrus) appear to be important in the complete sensation of pain, including the complex affective dimensions of pain. Figure 3 presents a diagram of the major parallel pathways carrying somatic sensory information to the cerebral cortex (see tutorial notes on “Mechanosensory Pathways”). The pathways for mechanoreception and the pathways for pain and temperature sensation shown in Figure A1 are shown together bilaterally.

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Figure 1. Organization of the central pathways for pain and temperature sensation. These pathways also carry crude information about touch. (As discussed an earlier tutorial, there is a small input into the trigeminal nuclei from the seventh, ninth and tenth nerves, but this input is of little significance clinically.) (Illustration by N.B. Cant)

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Spinal Spinal Dorsal trigeminal trigeminal horn tract nucleus

Anterolateral Cervical spinal cord system Anterolateral system

Caudal medulla

Spinal Region of ventral Spinal trigeminal trigeminothalamic trigeminal tract tract nucleus

Anterolateral system

Middle medulla

Figure 2. Location of the anterolateral system in the cervical cord and brainstem, with the ventral trigeminothalamic tract, as seen in cross-sections. Note that at all levels, the fibers of both tracts are located in the anterolateral part of the brainstem tegmentum (second-order neurons are illustrated in white). (Sections from Sylvius4) (Figure continued on next page)

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Spinal trigeminal Region of ventral nucleus & tract trigeminothalamic tract

Anterolateral system

Caudal pons

Region of ventral trigeminothalamic tract

Midbrain Anterolateral system

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Figure 3. A diagram of the major parallel pathways carrying somatic sensory information to the cerebral cortex. The pathways for mechanoreception and the pathways for pain and temperature sensation are shown together bilaterally in this figure. See related figures labels of nuclei and tracts. (Illustration by N.B. Cant)

6 Pain Pathways • Spring 2013 Pathways for pain, temperature and a crude sense of touch.

First-order Second-order Decussation Pathway Receptors Third-order neurons Primary cortical area neurons neurons pattern anterolateral systems free nerve endings in ipsilaterali DRGs ipsilateral dorsal horn of first pain pathway: first pain pathway: contralateral S1 spinal cord: second- somatic tissues and (dorsal root ganglion spinal cord: contralateral ventral Brodmann’s Areas 3, 1 & 2 order axons of dorsal viscera posterior complex of the horn neurons cross (for postcranial body, neurons) • superficial laminae lower extremity is represented in thalamus: • the midline in the including the posterior (marginal zone and the paracentral lobule substantia • ventral posterior ventral white portion of the head) Aδ & C afferent fibers gelatinosa) lateral (VPL) nucleus • upper extremity is represented commissure near the in the Ω-shaped segment of the segment of origin • deeper laminae at second pain pathways: [see Figures 10.6A and postcentral gyrus near the and ascend the base of dorsal horn contralateral targets in 10.5] middle of the central suclus neuraxis as the brainstem and thalamus: • nociceptive stimuli are localized spinothalamic tract • reticular formation via the somatotopic and various (spinoreticular tract) representations in S1 components of the anterolateral system • periaqueductal gray second pain pathways: that terminate in the (spinomesencephalic contralateral anterior cingulate brainstem tract) gyrus, insula, orbital-medial • nucleus of the prefrontal cortex, amygdala, solitary tract hypothalamus (components of the • intralaminar thalamic “limbic forebrain” that process nuclei affective signals) spinal trigeminal free nerve endings in ipsilateral trigeminal ipsilateral spinal first pain pathway: first pain: contralateral S1 pons and medulla: system somatic tissues and ganglion neurons in nucleus of the contralateral ventral Brodmann’s Areas 3, 1 & 2 second-order axons viscera trigeminal (gasserian) trigeminal complex in posterior complex of the of the spinal nucleus face is represented in the inferior ganglion the dorsal-lateral pons thalamus: • cross the midline and (for face—anterior third segment of the postcentral gyrus (caudal) and medulla • ventral posterior ascend the brainstem of head) nociceptive stimuli are crudely medial (VPM) • as the trigemino-

nucleus localized via the somatotopic thalamic tract, which [see Figure 10.6B and representations in S1 occupies a position second pain pathway: 10.5] near the fibers of the contralateral targets in second pain: contralateral components of the “limbic system” anterolateral system brainstem and thalamus (same as above) (same as above) dorsal column visceral free nerve endings in ipsilateral DRGs ipsilateral intermediate ipsilateral dorsal column contralateral insula supplied by a caudal medulla: pain pathwayii viscera gray of spinal cord (near nucleiiii: fourth-order relay in the ventral internal arcuate (see Box 10C) central canal) • gracile nucleus posterior complex of the thalamus fibers that give rise (different part than VPL) to medial lemniscus • cuneate nucleus

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i In this Table, the terms ipsilateral and contralateral will refer to the side of the peripheral or central nervous system relative to the location of the sensory receptors; e.g., cortical representation of first pain conveyed via Aδ axons occurs in the contralateral primary somatic sensory cortex. ii This newly discovered pathway processes visceral pain signals derived from thoracic and abdominal viscera in parallel with projections that contribute to the anterolateral system (e.g., the visceral pain signals that are conveyed via anterolateral system axons to the caudal part of the nucleus of the solitary tract). iii Visceral pain signals may be processed by different neurons in the dorsal column nuclei than those that respond to light, discriminative touch. However, there may be some dorsal column neurons that receive both visceral and non-visceral signals; these neurons could also provide a neural substrate for referred pain sensations, in addition to the mechanism that is usually described in the dorsal horn of the spinal cord (see Box 10B).

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