Pain Pathways Medical Neuroscience Tutorial Pain Pathways MAP TO NEUROSCIENCE CORE CONCEPTS 1 NCC1. The brain is the body's most complex organ. NCC3. Genetically determined circuits are the foundation of the nervous. 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 from peripheral nerve ending to cerebral cortex. 2. Recognize components of the anterolateral in the spinal cord, brainstem, thalamus and cerebral cortex. 2 3. Characterize the organization of the trigeminal pain & temperature (spinal trigeminal) from peripheral nerve ending to cerebral cortex. 4. Recognize components of the trigeminal pain & temperature (spinal trigeminal) in the brainstem, thalamus and cerebral cortex. 1 TUTORIAL NARRATIVE Introduction There are two major, parallel s that convey somatic sensory information from the periphery of the postcranial body to the cortex, the dorsal column-medial lemniscus and the anterolateral. There are comparable parallel s carrying information from the face associated with the central projections of the trigeminal nerve. In addition, there is an important carrying proprioceptive information from the muscle spindles to the cerebellum. This tutorial will focus on the pathways taken by the components of the s 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, 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 (e.g., in Sylvius4) so that you can recognize where relevant nuclei and axonal tracts are located within the brain and spinal cord. 1
Pain Pathways Spring 2013 Pathways mediating pain and temperature sensation. The anterolateral is responsible for conveying information about pain, temperature and crude touch (i.e., touch lacking the spatial resolution of the dorsal column ) 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 are free. That is, they are not associated with encapsulated endings like those in the dorsal column-medial lemniscal. In addition, the first-order fibers associated with the anterolateral are generally much smaller in diameter than those associated with the dorsal column. (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, like those in the dorsal column-medial lemniscal, have their cell bodies in the dorsal root ganglia. The central processes of these neurons terminate on secondorder 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. These neurons also project to central parts of the medulla, pons and midbrain known collectively as the reticular formation (this component of the anterolateral 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. 2
Pain Pathways Spring 2013 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) 3
Pain Pathways Spring 2013 Spinal trigeminal tract Dorsal horn Spinal trigeminal nucleus Cervical spinal cord Caudal medulla Spinal trigeminal tract Region of ventral trigeminothalamic tract Spinal trigeminal nucleus Middle medulla Figure 2. Location of the anterolateral 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) 4
Pain Pathways Spring 2013 Spinal trigeminal nucleus & tract Region of ventral trigeminothalamic tract Caudal pons Region of ventral trigeminothalamic tract Midbrain 5
Pain Pathways Spring 2013 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
Pathways for pain, temperature and a crude sense of touch. Pain Pathways Spring 2013 Pathway Receptors First-order neurons Second-order neurons Third-order neurons Primary cortical area Decussation pattern anterolateral s (for postcranial body, including the posterior portion of the head) [see Figures 10.6A and 10.5] free nerve endings in somatic tissues and viscera ipsilateral i DRGs (dorsal root ganglion neurons) Aδ & C afferent fibers ipsilateral dorsal horn of spinal cord: superficial laminae (marginal zone and substantia gelatinosa) deeper laminae at base of dorsal horn first pain pathway: contralateral ventral posterior complex of the thalamus: ventral posterior lateral (VPL) nucleus second pain pathways: contralateral targets in brainstem and thalamus: reticular formation (spinoreticular tract) periaqueductal gray (spinomesencephalic tract) nucleus of the solitary tract intralaminar thalamic nuclei first pain pathway: contralateral S1 Brodmann s Areas 3, 1 & 2 lower extremity is represented in the paracentral lobule upper extremity is represented in the Ω-shaped segment of the postcentral gyrus near the middle of the central suclus nociceptive stimuli are localized via the somatotopic representations in S1 second pain pathways: contralateral anterior cingulate gyrus, insula, orbital-medial prefrontal cortex, amygdala, hypothalamus (components of the limbic forebrain that process affective signals) spinal cord: secondorder axons of dorsal horn neurons cross the midline in the ventral white commissure near the segment of origin and ascend the neuraxis as the spinothalamic tract and various components of the anterolateral that terminate in the brainstem spinal trigeminal (for face anterior third of head) [see Figure 10.6B and 10.5] free nerve endings in somatic tissues and viscera ipsilateral trigeminal ganglion neurons in trigeminal (gasserian) ganglion ipsilateral spinal nucleus of the trigeminal complex in the dorsal-lateral pons (caudal) and medulla first pain pathway: contralateral ventral posterior complex of the thalamus: ventral posterior medial (VPM) nucleus second pain pathway: contralateral targets in brainstem and thalamus (same as above) first pain: contralateral S1 Brodmann s Areas 3, 1 & 2 face is represented in the inferior segment of the postcentral gyrus nociceptive stimuli are crudely localized via the somatotopic representations in S1 second pain: contralateral components of the limbic (same as above) pons and medulla: second-order axons of the spinal nucleus cross the midline and ascend the brainstem as the trigeminothalamic tract, which occupies a position near the fibers of the anterolateral dorsal column visceral pain pathway ii (see Box 10C) free nerve endings in viscera ipsilateral DRGs ipsilateral intermediate gray of spinal cord (near central canal) ipsilateral dorsal column nuclei iii : gracile nucleus cuneate nucleus contralateral insula supplied by a fourth-order relay in the ventral posterior complex of the thalamus (different part than VPL) caudal medulla: internal arcuate fibers that give rise to medial lemniscus 7
Pain Pathways Spring 2013 i ii iii In this Table, the terms ipsilateral and contralateral will refer to the side of the peripheral or central nervous 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. This newly discovered pathway processes visceral pain signals derived from thoracic and abdominal viscera in parallel with projections that contribute to the anterolateral (e.g., the visceral pain signals that are conveyed via anterolateral axons to the caudal part of the nucleus of the solitary tract). 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). 8