Neuroanatomy Pain and Temperature

Somatosensory II: Pain and Temperature

Competencies:

Describe the physiological and structural characteristics of the two primary sensory neurons that transmit pain and temperature sensations to the central nervous system.
Compare the central connections within the spinal cord and the second order projections of A-delta- and C-fibers.
Appraise the organization of pars caudalis of the spinal nucleus of trigeminal nerve and the projections to the nucleus.
Associate specific higher brain centers with the behavioral responses to acute and chronic pain.
Provide examples of how higher brain centers modulate the transmission of pain stimuli within the CNS.

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Purves text, Chapter 10
Haines pp 192, 198.

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Pain (nociception) has both a sensory/discriminative aspect and a motivational/affective aspect (e.g. suffering). These different aspects of pain are localized to parallel systems that arise in the periphery and enter the spinal cord together but ultimately take separate paths (in part) and activate different systems within the CNS.
The sensation of pain and temperature is mediated by free nerve endings.
Free nerve endings have no obvious morphological end organ specializations, yet different free nerve endings are selectively sensitive to very different types of stimuli. Nociceptors (pain receptors) may be high threshold mechanoreceptors, high threshold thermoceptors, chemoceptors (sensitive to chemicals applied to the skin), or polymodal. Others are termed "silent", and do not appear to respond to any stimuli (other than shock which activates everything) until frank damage to tissue has occurred. Similarly, low threshold thermoceptors may be sensitive to warmth or coolness, but generally not both. Heat and cold are coded by subtypes of TRP (transient receptor potential) cation channels that are differentially sensitive to warmth or coolness, sensations that can be elicited by either capsaicin or menthol.
Cell bodies of the receptors are in the dorsal root ganglia (DRG). The central processes of the afferents enter the spinal cord via the lateral aspect of the dorsal root.
The peripheral (primary) afferent fibers of free nerve endings are all small diameter, and all are either thinly myelinated (A δ , or group III fibers), or unmyelinated (C, or group IV fibers).
- A δ = myelinated, fast pain fibers (A δ - conduction velocity ~ 20 m/s). Conveys acute, sharp, localizable pain.
- C = unmyelinated, slow pain fibers (C - conduction velocity ~ 2 m/s). Conveys chronic painful stimuli, difficult to localize, slow to adapt.
Differences in conduction velocity contribute to the phenomenon of double pain; i.e. first, pain is sharp, and well localized followed by secondary pain sensations that are more burn-like and less well localized.
In this case, the lighter tract represents the basic pain pathways (darker, conscious touch). Pain fibers enter Lissauer’s Tract at the dorsal edge of the dorsal horn and bifurcate, running up and down the cord two or three segments before entering the grey matter and synapsing on dorsal horn neurons.
A δ fibers terminate monosynaptically primarily on neurons in the Marginal Zone (lamina I) and lamina V. C fibers terminate monosynaptically on neurons of lamina I (C fibers from the skin may terminate on neurons within the superficial edge of lamina II, the substantia gelatinosa) and polysynaptically on neurons of lamina V.
Lamina I neurons comprise several morphologically and neurochemicallly distinct, modality-selective classes that receive input from selective subsets of A δ and C fibers and thus communicate the specific physiological states of the tissues of the body.
Lamina V neurons have large dendritic fields that extend across most of the dorsal horn and provide an integrative representation of all primary afferent input from large receptive fields.
Small, local circuit neurons within the substantia gelatinosa receive input not only from C fibers but also from neurons of the brainstem and hypothalamus that modulate the activity of projection neurons in lamina V. Significant information processing occurs within the substantia gelatinosa that serves to either “dampen” incoming noxious stimuli or “sensitizes” silent neurons to those noxious inputs.
Substance P, CGRP, and other peptides contribute to neurotransmission at the synapse between C fibers and substantia gelatinosa neurons. Amino acids, such as glutamate and aspartate and possibly other peptides may mediate responses from A d nociceptors. These neurochemical signatures not only specify the type of information being transmitted from the periphery (fast, sharp pain vs slow, burning pain) but where that information may be transmitted within the CNS.
About 90% of the axons arising from lamina I neurons and 50% of the axons arising from lamina V cross the midline via the anterior (ventral) white commissure, just under the central canal area, and ascend in the anterolateral quadrant as the anterolateral system of tracts. Crossing occurs over approximately 2-3 segments, which has clinical implications for determining the level of a lesion by loss of pain and temperature sensitivity. Many lamina V neurons involved in the transmission of crude touch and proprioception ascend ipsilaterally in the ventral medial funiculus.
The classic neospinothalamic tract, carrying information regarding fast, sharp, well localized pain that was transmitted by the A δ fibers, is comprised of axons arising from cell bodies in lamina I that cross the midline in the anterior white commissure and ascend ventrolaterally in a somatotopic manner directly to the ventral posterolateral thalamus.
The third order neurons of the neospinothalamic tract system are somatotopically organized in the ventral posterior lateral nucleus of the thalamus. The axons of these neurons exit the thalamus via the posterior limb of the internal capsule and terminate in the primary somatosensory cortex at the postcentral gyrus (SI), as well as the adjacent secondary somatosensory cortex (SII) and the retroinsular region. A somatotopic homunculus, similar to that of the medial lemniscal system is found here.
The so-called paleospinothalamic tracts which mediate the slower, burning, aching and affect-altering information transmitted by C fiber stimulation is comprised primarily of axons arising from morphologically distinct cell bodies in lamina I. Much of the information carried by these projections may not be somatotopically organized and end in intralaminar thalamic nuclei as opposed to the VPL. Other fibers, either direct projections or branches of spinal thalamic afferents, project into homeostatic (parasympathetic) regions of the reticular core of the medulla and pons (spinal reticular projections) as well as into the midbrain periaqueductal grey (PAG) and raphe nuclei (spinal mesencephalic projections). Propriospinal projections also reach to the sympathetic preganglionic neurons of the intermediolateral cell column.
Most of the paleospinothalamic system terminates in the midline and intralaminar thalamic nuclei, although some project directly to limbic cortex (e.g. anterior cingulate and insular cotex, amygdala). The axons of many of these thalamic neurons project then project primarily to (SII) and the anterior cingulate cortex, with a more minor projection to SI. The projections to SII, insular and cingulate cortex, as well as the amygdale, are primarily involved in the emotional-motivational aspects of pain.
Many other areas of cortex also receive input from this system, explaining why ablation of the primary somatosensory cortex does not disrupt pain or suffering, but only may affect the ability to locate the pain on the body.
Brainstem and forebrain regions that receive noxious information all form components of the descending system that modulates activity at the level of the spinal cord. There are many models that describe components of this modulatory activity. For example, neurons in the PAG project to and activate neurons in the medullary raphe nuclei which send axons down to the dorsal horn of the spinal cord via the raphespinal tract. These axons can release serotonin which can inhibit pain transmission to higher centers. The PAG is also important in the analgesic effects of opioids, such as morphine. Portions of the spinoreticular tract also activate descending pain modulatory systems, such as the descending pathways from noradrenergic pontine locus coeruleus and other lateral medullary centers such as the nucleus reticullaris paragigantocellularis. These pathways travel with the raphespinal tract in the dorsolateral funiculi of the spinal cord and terminate in the dorsal horn to inhibit pain information.
There are other direct and indirect projections from the hypothalamus, basal forebrain and amygdala. In subsequent lectures, we will learn how these spinomesencephalic and spinoreticular projections recruit widespread areas of the brain in what is observed as arousal and attention responses to painful stimuli.
Painful stimuli from the face are transmitted in a topographically organized fashion via the three divisions of the trigeminal (V) nerve (ophtalmic, maxillary and mandibular - information from the ear and pharynx are carried by components of N7, 9 and 10).
First order neurons descend ipsilaterally from the pons into the medulla via the spinal trigeminal tract. Especially in the lower medulla caudal to the obex, this tract lies in a prominent position on the lateral surface of the medulla.
The primary axons arising from the part of the head closest to the C2 dermatome (i.e. the crown of the head to the mandible and neck) from all three divisions will descend to the spinal-medullary junction. First order axons from all three divisions will descend to progressively more rostral levels in the medulla as the somatotopic pattern progresses toward the nose and oral invagination.
The first order axons terminate in the spinal nucleus of five. Especially in sections through the lower medulla, the appearance of the spinal nucleus is similar to the substantia gelatinosa of the spinal cord. The primary afferents terminate in synaptic arrangements similar to that seen in the marginal zone and substantia gelatinosa of the spinal cord.
Secondary fibers project from the spinal trigemimal nucleus and diffusely cross to the contralateral brainstem to form the ventral trigeminothallamic tract (it will lie just lateral to the dorsal part of the medial lemniscus in medulla and take a position medial and dorsal to the medial lemniscus in the pons). These second order axons terminate in ventral posteromedial thalamic nucleus.
Painful stimuli from the face are modulated by reticular and limbic sources in a manner similar to that seen in the spinal cord.

Consider the Following Questions ...

Describe the receptors, nerve, and pathways for perceiving pain on the body and face.
Describe the consequences of a lesion in the upper medulla that interrupts the spinal tract of the trigeminal nerve and the spinothalamic tract.
Describe the consequences of a lesion on the left side of the spinal cord at mid-thoracic levels with respect to the perception of touch and acute pain on the legs.
Describe the impact of myelination upon speed of axon conduction, and characterize the thickness of myelination for: 1. slow pain fibers; 2. Golgi tendon organs; 3. Pacinian corpuscles.
Name the thalamic nucleus receiving the medial lemniscus and spinothalamic tracts, and describe the somatotopic organization of the terminals from these tracts.
The secondary axon in an ascending sensory pathway tends to cross to the opposite side. For proprioception, this crossing takes place at what level of CNS? For pain, this crossing takes place at what level of CNS?
Describe the consequences of a lesion in the upper medulla that interrupts the spinal tract of the trigeminal nerve and the spinothalamic tract.
Describe the origins of the ventral trigeminothalamic tract and the synaptic destination in thalamus.