The CNS and normal neuromuscular and musculoskeletal function Week 2 Flashcards
How does pain occur ?
Pain occurs when sensory nerve endings called nociceptors (also referred to as pain receptors) come into contact with a painful or noxious stimulus. The resulting painful impulse travels from the sensory nerve ending, enters the dorsal spinal cord, and travels to diverse parts the brain via nerve tracts in the spinal cord and brainstem. The brain processes the pain sensation and quickly makes a motor response in an attempt to cease the action causing the pain.
What are somatosensory pathways ?
Sensory pathways consist of the chain of neurons, from receptor organ to cerebral cortex, that are responsible for the perception of sensations.
The sensory information processed by the somatosensory systems travels along different anatomical pathways depending on the information carried.
For example, the posterior column-medial lemniscal pathway carries discriminative touch and proprioceptive information from the body, and the main sensory trigeminal pathway carries this information from the face. Whereas, the spinothalamic pathways carry crude touch, pain and temperature information from the body, and the spinal trigeminal pathway carries this information from the face.
What are the common features in a somatosensory pathway ?
Within each somatosensory pathway,
-The 1° afferent is a pseudounipolar neuron that has its cell body located in a peripheral (spinal or cranial) ganglion. It has a peripheral axon that forms or innervates somatosensory receptors and a central process that synapses with 2° afferent neuron(s) in a spinal cord or brain stem nucleus.
-The 2° afferent may synapse with 3° afferent neurons in the spinal cord or may ascend the neuraxis to synapse with 3° afferent neurons in the thalamus.
-There is a decussation (i.e., axons crossing the midline to the opposite side of the spinal cord or brain stem) in each somatosensory pathway below the level of the thalamus.
-All somatosensory pathways include a thalamic nucleus. The thalamic neurons send their axons in the posterior limb of the internal capsule to end in the cerebral cortex.
Most somatosensory pathways terminate in the parietal lobe of the cerebral cortex.
Describe the different somatosensory axons ?
-The Group I and II 1° afferent axons, which form the muscle/tendon receptors and carry body proprioceptive information, have the largest diameter and the thickest myelin of all the somatosensory 1° afferent axons.
-The Type C 1° afferent axons, which form free nerve endings and carry dull pain, deep pain, crude touch or warm/hot information, are the smallest 1° afferent axons and are unmyelinated.
-The Type Aδ1° afferent axons, which form free nerve endings and carry sharp pain or cool/cold information, are thinly myelinated and larger than the Type C axons.
-The Type Aβ 1° afferent axons, which form encapsulated endings in skin and joints or hair follicle endings or Merkel disks in skin, are myelinated and have diameter less than Group I afferents and greater than the Type Aδ 1° afferent axons.
Which peripheral axons have the greatest conduction velocity ?
-the larger and more heavily myelinated the axon, the greater its conduction velocity
-Consequently, the 1° afferent axons carrying information required for fine motor control and rapid reflex responses (i.e., those forming body proprioceptors) conduct action potentials rapidly, whereas those carrying information about body and object temperature conduct action potentials at a much slower rate
What are the two main classes of nerve fibers associated with the transmission of pain ?
There are two major classes of nerve fibers associated with the transmission of pain:
-Unmyelinated C fibers (small and slow)
-Myelinated A-delta fibers (myelinated and fast)
Unmeylinated C fibers:
- The unmyelinated C fibers respond to thermal, mechanical, and chemical stimuli and produce the sensation of dull, diffuse, aching, burning, and delayed pain.
Myelinated A -delta fibers:
-The myelinated A-delta fibers respond to mechanical (pressure) stimulus and produce the sensation of sharp, localized, fast pain.
What is the spinothalamic tract ?
One of the most important central pain pathways is the spinothalamic tract, which originates in the spinal cord and extends to the thalamus. This spinal tract transmits sensory information related to pain, temperature, and crude touch. Another prominent pathway is the spinoreticular tract, which is involved in nociceptive processing. The spinoreticular tract is similar to the spinothalamic tract in that it is excited by similar sensory fibers. Rather than ascending to the thalamus however, spinoreticular neurons terminate within the brainstem reticular formation
What is pain ?
What is nociception ?
Is pain good or bad ?
Characterizing pain based on its origin in the body and duration
- We can categorize pain into visceral pain and soamtic pain.
- Visceral pain normally occurs in organs of the thorax and abdominal cavity. Normally very poorly localized, we don’t always know exactly where the pain is coming from.
- Somatic pain we normally feel on our skin, muscles, joints…..
this type of pain is more localized and we can normally tell where the pain is coming from - We can also categorise pain based on the duration of how long it lasts for. Acute and chronic pain.
Describe the general pain pathway ?
- This information ascends upwards using first, second, and third-order neurons.
- First-order neurons receive impulses from skin and proprioceptors and send them to the spinal cord. They then synapse with second-order neurons. Second-order neurons live in the dorsal horn and send impulses to the thalamus and cerebellum
- Lastly, third-order neurons pick up these impulses in the thalamus and relay it to the somatosensory portion of the cerebrum. Somatosensory sensations are pressure, pain, temperature, and the body’s senses.
First-order neurones :
-These are pseudounipolar neurones which have cells bodies within the dorsal root ganglion.
-They have one axon which splits into two branches, a peripheral branch (which extends towards the peripheries) and a central branch (which extends centrally into the spinal cord/brainstem).
Second-order neurones:
-The cell bodies of these neurones are found in the Rexed laminae of the spinal cord, or in the nuclei of the cranial nerves within the brain stem.
- These neurones then decussate in the anterior white commissure of the spinal cord and ascend cranially in the spinothalamic tract to the ventral posterolateral (VPL) nucleus of the thalamus.
Third-order neurones:
-The cell bodies of third-order neurones lie within the VPL of the thalamus.
-They project via the posterior limb of the internal capsule to terminate in the primary somatosensory cortex.
- The primary somatosensory cortex is somatotopically organized. -
-Therefore, pain signals initiated in the hand will terminate in the area of the cortex dedicated to sensations of the hand.
What is the somatosensory cortex ?
-The somatosensory cortex is a region of the brain which is responsible for receiving and processing sensory information from across the body, such as touch, temperature, and pain.
- Located: in the postcentral gyrus of the parietal lobe, and lies behind the primary motor cortex of the frontal lobe.
- The somatosensory cortex receives tactile information from the body, including sensations such as touch, pressure, temperature, and pain. This sensory information is then carried to the brain via neural pathways to the spinal cord, brainstem, and thalamus.
-This information is then projected to the somatosensory cortex, which in turn has numerous connections with other brain areas in order to process the sensory information.
-The somatosensory cortex uses sensory information to initiate important movements that may be required to deal with particular situations.
Describe the somatosensory pathway ?
Somatosensory pathways are typically comprised of three neurons: primary, secondary, and tertiary.
The primary neurons are the sensory receptors within the periphery of the somatosensory cortex which are able to detect various stimuli such as touch or temperature. The secondary neurons are located within the spinal cord and brainstem and act as a relay station.
Afferent pathways (which carry signals to the central nervous system) in the spinal cord and brainstem working by passing information from the periphery and the rest of the body to the brain. These will then terminate in either the thalamus or the cerebellum.
The tertiary neurons, which are located within the thalamus and cerebellum, will then project to the somatosensory cortex. This will then aid in forming a sensory homunculus, which is a representational map of the body.
Understand the anatomy and physiology of nociceptors and the ‘pain pathways’
-Some first-order neurones have specialist receptors called nociceptors which are activated through various noxious stimuli.
-Nociceptors exist at the free nerve endings of the primary afferent neurone.
- Since nociceptors are free nerve endings this means they are unencapsulated cutaneous receptors
-Similar to other sensory modalities, each nociceptor has its own receptive field. This means one nociceptor will transduce the signal of pain when a particular region is skin is stimulated. The size of receptive fields varies throughout the body and there is often overlap with neighbouring fields.
-Areas such as the fingertips have smaller receptive fields than areas such as the forearm. In addition, they have a larger density of free nerve endings within this receptive field. This difference is important as it allows for greater acuity in detecting a sensory stimulus.
-The size of cortical representation in the somatosensory cortex of a particular body part is also related to the size of the receptive fields in that body part. For example, because the fingertips have small receptive fields, and thus a greater degree of sensory acuity, they have a larger cortical representation.
Types of nociceptors ?
Nociceptors can be found in the skin, muscle, joints, bone, and organs (other than the brain) and can fire in response to a number of different stimuli. Different types of nociceptors exist:
-Mechanical nociceptors – detect the distension of skin (stretch) and pressure which elicit sharp, pricking pain.
-Chemical nociceptors – detect exogenous and endogenous chemical agents, such as prostanoids, histamines etc.
-Thermal and mechano-thermal nociceptors – detect thermal sensations that elicit slow and burning, or cold and sharp in nature, pain.
Polymodal nociceptors – detect mechanical, thermal, and chemical stimuli.
Silent receptors are dormant in normal joints and will be unresponsive to stimuli such as heat or pressure. They become responsive only after tissue damage causes the release of inflammatory molecules in conditions such as arthritis. It is believed that patients with arthritis often complain of joint pain at rest due to these receptors suddenly becoming active and causing spontaneous neuronal firing. Additionally, these silent nociceptors may become mechanosensitive following inflammatory induction and can then contribute to pain with movement in patients with arthritis.
Primary afferent fibers (axons) ?
- Primary afferents are sensory neurons (axons or nerve fibers) in the peripheral nervous system that transduce information about mechanical, thermal, and chemical states of the body and transmit it to sites in the central nervous system.
- Primary afferent sensory neurons are the gateway by which sensory information is transmitted from the peripheral tissues to the spinal cord and brain
- The cell bodies of primary afferent sensory nerve fibers are located in the dorsal root ganglia (DRG) and trigeminal ganglia.
- Anatomically, there are two broad groups of sensory nerve fibers: myelinated A-fibers and smaller diameter, unmyelinated C-fibers
- the large diameter axons which are A (alpha) and A (beta) are very rapidly conducting. They are mainly associated with low threshold mechanoreceptors so touch
- Pain and temperature nociceptors have A (delta) fibers.
- Polymodal nociceptors have C fibers.
What is a pseudounipolar neuron ?
- A pseudounipolar neuron is a type of neuron which has one extension from its cell body. This type of neuron contains an axon that has split into two branches.
- Pseudounipolar neurons are sensory neurons that have no dendrites, the branched axon serving both functions. The peripheral branch extends from the cell body to organs in the periphery including skin, joints and muscles, and the central branch extends from the cell body to the spinal cord
Different types of afferent receptors ?
Alternatively, in the sensory system, afferent fibers can be classified by sizes with category specifications depending on if they innervate the skins or muscles
Describe primary afferent fibers: c type ?
- The majority of primary afferent neurons that transmit noxious stimuli are C-fibers which can be divided into two different classes.
Peptide rich C fibers:
- In the adult, peptide-rich C-fibers express neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP), are regulated by nerve growth factor (NGF) and express tyrosine receptor kinase A (trkA), the cognate receptor for NGF.
-These fibers are largely nociceptive and terminate more superficially within the dorsal horn
Peptide poor C fibers:
- the peptide-poor C-fibers contain the enzyme fluoride-resistant acid phosphatase and selectively bind the lectin Griffonia simplicifolia isolectin B4 (IB4)
-Additionally these nerve fibers express the purinergic receptor known as P2X3 , and respond to glial cell line-derived neurotrophic factor (GDNF) as they express the GDNF receptor complex, which includes glial cell line-derived factor receptor (GFR-alpha) subunits and receptor tyrosine kinase c-Ret (c-RET) .
-These peptide-poor nerve fibers terminate almost exclusively within the deeper parts of lamina II of the spinal dorsal horn
Describe first and second pain ?
- The two different types of fibers that transmit nociception, Alpha (delta) and C fibers do so at different speeds.
- First pain is transmitted by the A (delta fibers)
- Second pain is transmitted by the C fibers.
Transduction of pain:
- different noxious stimuli will open different receptors channels
- Eg. Capsaicin binds to TRPV1 receptor
-Eg. Menthol binds to TRPM8 receptor
Eg. Mustard oil binds to TRPA1 receptor
Nociceptive stimuli activate TRP channels located on nerve endings, which cause first-order neurons to depolarize and fire action potentials. Action potential frequency determines stimulus intensity. A delta fibers release glutamate onto second-order neurons, while C fibers release neuropeptide neurotransmitters. First-order neurons are found in the dorsal root ganglion (stimulus from the body) and trigeminal ganglia (stimulus from the face).
Transduction of pain basic
- The free nerve endings activate different receptor types. This generates a receptor potential which depolarizes the membrane.
- The cell bodies are located in the dorsal root ganglion.
- The action potential enters the spinal chord via the dorsal horn.
- There are sodium channels on the nociceptor. Mutations in these can lead to congenital analgesia.
What is congenital analgesia ?
Congenital insensitivity to pain is a condition that inhibits the ability to perceive physical pain. From birth, affected individuals never feel pain in any part of their body when injured
The sodium channel in a nociceptor can be blocked, which reduces pain
Transmission of the primary afferent in the spinal cord ?
The pathway is known as the spinothalamic ( nociceptive pathway)
- Signals from mechanical, chemical, thermal, and mechano-thermal nociceptors are transmitted to the dorsal horn of the spinal cord predominantly via Aδ fibres. These myelinated fibres have a low threshold for firing and a fast conduction speed. Hence, they are responsible for transmitting the first pain felt.
In addition, Aδ fibres permit the localisation of pain and form the afferent pathway for the reflexes elicited by pain.
Aδ fibres predominantly terminate in Rexed laminae I where they mainly release the neurotransmitter, glutamate.
Polymodal nociceptors transmit their signals into the dorsal horn through C fibres. C fibres are unmyelinated and a slow conduction speed. For this reason, C fibres are responsible for the secondary pain we feel which is often dull, deep, and throbbing in nature. These fibres typically have large receptive fields and therefore lead to poor localisation of pain.
Compared to Aδ fibres, C fibres have a high threshold for firing. However, noxious stimuli can cause sensitisation of C fibres and reduce their threshold for firing.
C fibres predominately terminate in Rexed laminae II (known as substantia gelatinosa) and release the neurotransmitter substance P.
Other neurotransmitters are released by primary afferent neurons terminating within the spinal cord such as aspartate and vasoactive peptide.