L.2.2 Flashcards
what are primary sensory nerve fibres
nerve fibres that transmit different sensory modalities (ex: chemical, mechanical or thermal)
What are the features of large sensory nerve fibres
- conduct signals more quickly
- faster signal transmission
Why do large primary sensory nerve fibres conduct signals faster
- greater diameter (less resistance)
- more myelination
What are examples of large primary sensory nerve fibres
proprioception and touch fibres
What are features of small sensory nerve fibres
- conducts signals more slowly
- slower signal transmission
Why do small sensory nerve fibre conduct signals slower
- they have a smaller diameter (more resistance)
- little to myelination
What is the function of tactile receptors close to the surface of the skin
- important for detecting light touch and texture
Name 2 tactile receptors that are close to the surface of the skin
- Merkel’s disk
- Meissner’s corpuscle
What is the function of deeper tactile receptors
specialised for sensing deeper pressure and skin stretching
What are the differences in receptive field size between tactile receptors
- close to surface: small receptive fields
- deep: large receptive fields
What does the size of the receptor field mean
- small receptor field = smaller area of skin = allows more precision
- larger receptor field = larger skin area = no precision and allows gross movement
What are rapid adapting receptors
- respond strongly at the start of stimulus and continue even if the stimulus is gone
- good for detecting changes in stimuli
What are the slowly adapting receptors
- continue to fire as long as the stimulus is present
- good for detecting continuous pressure or stretch
How does mechanical transduction work
- touch is transduced by mechanically sensitive ion channels
- channels open to the deformation of the cell membrane by skin/receptors
- this leads to action potential
What are the 2 ways in which sensory information is coded by primary sensory neurons
- rate coding
- temporal coding
What is rate coding
- frequency of action potentials
How does rate coding code sensory information
- stronger stimulus = higher frequency of APs = higher rate of coding
What is temporal coding in sensory information processing?
- Temporal coding refers to the timing of action potentials
- helps to know when a stimulus occurs
How does the CNS interpret sensory information?
based on the rate (frequency) and timing (temporal coding) of action potentials
What is spatial resolution
the ability to distinguish between two close touches.
How is spatial distribution measured
using the 2-point discrimination test.
What is the significance of the 2-point discrimination test?
- can be used to assess nerve damage
- if nerve damage = can’t separate even at large distances
Why is the density of tactile receptors greater on the hand and face
it allows for better spatial resolution
How does the spatial distribution of tactile receptors vary across the body?
Some areas of the body have more tactile receptors than others, which affects sensitivity and spatial resolution
What is the difference between sensation and perception?
- Sensation: Direct result of activating sensory receptors
- Perception: brain’s interpretation of sensations, influenced by past experiences and emotions
Why can the same touch feel different depending on context?
Perceptions are influenced by past experiences and emotions
What are the two types of sensory information carried in ascending tracts?
- proprioceptive
- exteroceptive
What does proprioceptive information mean
information originating from inside the body (muscle, joints)
What does exteroceptive information mean
information originating from outside the body (pain, touch)
What are the 3 main neurons in the anatomy of the ascending sensory tracts?
- first-order neurons
- second-order neurons
- third-order neurons
What do first-order neurons do
they carry information by entering the spinal cord via the dorsal root ganglion
What do second-order neurons do
they carry information by ascending from the spinal cord to the brainstem
What do third order neurons do
they carry information from brainstem to the cortex
What does the dorsal column-medial lemniscus pathway transmit?
- fine touch
- vibration
- proprioception
- from the PNS to the brain
What is the mnemonic for the DCML Pathway
- Feeling Very Patient
What types of receptors are involved in proprioception?
muscle spindles, Golgi tendon organs, joints
Outline the DCML Pathway
- first-order neurons enter spinal cord via the fasciculus cuneatus & gracilis
- they ascend via dorsal column
- synapse & decussate w/ second-order neurons in medulla at the nucleus cuneatus and gracilis
- third order neurons project to somatosensory cortex
What is the function of the Fasciculus cuneatus & fasciculus gracilis
- Fasciculus cuneatus = carries upper limb sensation to nucleus cuneatus
- Fasciculus gracilis = carries lower limb sensation to nucleus gracilis
Where do first-order neurons synapse in the dorsal column pathway?
First-order neurons synapse on second-order neurons in the medulla at the nucleus cuneatus and nucleus gracilis
What is the function of second-order neurons, and where are they located? DCML Pathway
- Location: Medulla
- Receive input from first-order neurons, decussate (cross over), and form the medial lemniscus
What is the location and function of third-order neurons? DCML Pathway
- Location: Thalamus
- Project sensory input to the somatosensory cortex for interpretation
What is the location and function of first-order neurons in the dorsal column pathway?
- Location: Spinal cord (Fasciculus cuneatus & fasciculus gracilis)
- Receive sensory input from peripheral receptors and ascend through dorsal columns
What happens when the dorsal column (DCML) in the spinal cord is damaged?
Loss of tactile discrimination and proprioception on the same side as the damage
Why does damage to the dorsal column cause loss of sensation on the same side?
- sensory signals do not cross over until the medulla
- damage in the spinal cord interrupts signals from the same side before they decussate.
What is clinical test that can be used to determine if someone has had DCML damage
Romberg’s sign
What is the Rombergs sign test
- Tests for sensory ataxia
- present when a patient is able to stand with feet together and eyes open, but sways or falls with eyes closed
What is the spinothalamic tract responsible for
carrying non-discriminative touch, pain and thermal sensory information from the body the brain
Where do first-order neurons of the spinothalamic tract enter?
First-order neurons enter the spinal cord and form the tract of Lissauer.
where do first-order neurons synapse the spinothalamic tract
dorsal horn of the spinal cord
After crossing the spinal cord, where do second-order neurons travel? (spinothalamic tract)
They ascend in the anterolateral column of the spinal cord to the thalamus.
How are the fibres in the spinothalamic tract organized?
Lower limb fibres: Located laterally anterolateral column
Upper limb fibres: located anterior anterolateral column
What is the function of third-order neurons in the spinothalamic tract?
Project sensory information from the thalamus to the somatosensory cortex
What is the effect of a lesion of the spinal cord in the spinothalamic tract?
Loss of pain, temperature, and crude touch on the opposite side of the body.
Why does a lesion on one side of the spinal cord affect sensations on the opposite side? (spinothalamic tract)
they decussate in the spinal cord
What happens with outer tract injury (e.g., cord compression from a herniated disk)? (spinothalamic tract)
Loss of lower limb pain first, as lower limb fibers are located laterally.
What happens with inner tract injury (e.g., grey matter tumor)?
Loss of upper limb pain first, as upper limb fibers are located medially.
What kind of sensory information does the spinocerebellar tract carry
unconscious proprioceptive information from peripheral receptors (muscle spindles, Golgi tendon organs and joint capsules) to the cerebellum.
What are the effects if a lesion occurs at the spinocerebellar tract
- uncoordinated muscle activity on the same side
- the tract doesn’t cross over, damage affects the same side of the body
What are the 2 tracts that make up the spinocerebellar tract
- posterior (or dorsal) spinocerebellar tract
- anterior (or ventral) spinocerebellar tract
What is the function of the anterior (or ventral) spinocerebellar tract
involved in carrying proprioception from the lower limb
What is the function of the posterior (or dorsal) spinocerebellar tract
carries unconscious proprioceptive information from the lower limb and trunk
Outline the pathway of the spinocerebellar tract
1)First-order neurons enter the spinal cord and synapse in the dorsal horn
2)Second-order neurons ascend the lateral column to cerebellum via fast axons
What is pain?
An unpleasant sensory experience associated with tissue damage, involving both physical sensations and emotional reactions (e.g., fear and anxiety).
Why might two people experience the same injury differently?
Pain involves emotional reactions, which vary based on individual factors like past experiences and personal thresholds.
Why do we feel pain?
- Protective mechanism: Alerts the body to danger
- Prevent further damage: Encourages healing
- Learning: Emotional memory of pain helps avoid harmful situations.
What are the common sensations of pain?
sharp, itch & ache
Where do pain signals start in the body?
In nociceptors, located in the skin and muscles
What is the role of nociceptors in pain?
They detect harmful stimuli and send signals to the spinal cord via nerves.
How does the spinal cord contribute to pain processing?
It relays pain signals to the brain for further processing
Which brain regions process pain sensations and emotional responses?
- Somatosensory cortex: Processes the physical sensation of pain.
- Limbic system: Handles emotional responses to pain.
What are the two main components of pain mechanisms?
- Peripheral Component: Nociceptors detect harmful stimuli and send signals to the spinal cord.
- Central Component: The spinal cord relays signals to the brain, which processes the sensation and emotional reaction.
What is nociceptive pain?
Pain Caused by activation of nociceptors due to actual or potential tissue damage
What are examples of injuries that cause nociceptive pain?
Injuries to tissues such as skin, muscles, and joints
What is neuropathic pain?
Pain caused by injury or dysfunction of the nervous system, leading to abnormal pain signals
What are nociceptors?
Primary sensory neurons that detect pain
Where are nociceptors located?
- skin
- muscles
- meninges
How do nociceptors transmit pain signals?
Nociceptors send pain signals to the dorsal horn in the spinal cord, which then transmits them to the brain.
What are the two primary sensory nerve fibres for transmitting pain?
- A-delta fibres
- C fibres
What do A-delta fibres transmit
Transmit sharp and acute pain quickly (e.g., touching a hot surface).
What do C fibres transmit
Transmit dull and aching pain slowly.
Why are pain signals transmitted slowly via small-diameter nerve fibres?
To keep pain in the brain’s awareness longer, encouraging proper rest and avoiding further injury
What are free nerve endings?
Unspecialised nerve endings of nociceptors make them versatile in detecting a range of painful stimuli
What types of stimuli can nociceptors detect?
thermal, mechanical and chemical
what kind of special structure do nociceptors have
they have free nerve endings in the periphery
What are features of first-pain response
- well-localised
- fast transmission
- conducted by alpha-delta fibres
What are features of secondary pain responses
- poorly localised
- slow transmission
- conducted by C-fibres
What are polymodal nociceptors?
Nociceptors that respond to multiple types of stimuli, such as thermal and chemical.
What type of nociceptors are mostly polymodal?
C fibres
How does the brain differentiate between pain stimuli (e.g., heat or mechanical force)?
The central nervous system decodes signals from peripheral nerves to determine the pain source.
What is pressure transduction in nociceptors?
Mechanically sensitive ion channels at the nerve receptor ends respond to pressure, causing membrane deformation
What happens during pressure transduction?
- Membrane deformation causes ion channels to open
- Calcium and sodium ions enter the cell, causing depolarization.
- Action potential generated
What channels are responsible for temperature transduction?
Transient receptor potential (TRP) channels transduce different temperatures
Which specific TRP channel responds to heat and capsaicin?
The Vanilloid (TRPV1) channel responds to heat and capsaicin (found in chillies)
How does inflammation affect nociceptors?
Inflammatory chemicals released during tissue injury excite nociceptors, enhancing pain sensitivity.
What are examples of chemicals that sensitize nociceptors during inflammation?
- ATP
- H+
- serotonin
What happens to nociceptors during tissue injury or inflammation?
Chemicals are released that activate nociceptors, triggering pain signals.
Which chemical binds to purinergic receptors to activate nociceptors?
ATP binds to purinergic receptors
Which chemical binds to 5-HT3 receptors to activate nociceptors?
serotonin
How do protons (H+) activate nociceptors?
Protons bind to acid-sensing channels and increase during tissue acidosis (ex: lactic acid build up during exercise)
What is neurogenic inflammation?
Activation of one branch of a nociceptor spreads inflammation to other areas
What chemicals are released during neurogenic inflammation?
Substance P and calcitonin gene-related peptide (CGRP).
What are the effects of Substance P and CGRP?
- Vasodilation: Blood vessels dilate, increasing blood flow.
- Mast Cell Activation: Mast cells release histamine, increasing inflammation.
What is hyperalgesia?
A condition where noxious stimuli produce an exaggerated pain response
What is allodynia?
A condition where non-noxious stimuli cause a painful response.
What is an example of hyperalgesia
A small pinch on inflamed skin feels extremely painful
What is an example of allodynia
Brushing against sunburned skin feels painful
Why does inflammation cause hypersensitivity?
Hypersensitivity protects injured tissues by preventing interference, promoting healing
What are the two main mechanisms of pain hypersensitivity?
- Peripheral sensitisation
- Central sensitisation
What is peripheral sensitisation
Increased responsiveness of nociceptor ends due to tissue injury/inflammation.
What is central sensitisation
Enhanced response within the spinothalamic tract, common in neuropathic pain.
How does bradykinin contribute to peripheral sensitisation?
- Reduces the threshold of heat-activated TRPV1 channels
- Causes heat-sensitive nociceptors to fire more easily, increasing sensitivity to warmth
How does nerve growth factor (NGF) affect nociceptors?
It reduces the threshold of TRPV1 channels, making heat-sensitive nociceptors fire more easily.
How do prostaglandins contribute to pain hypersensitivity?
- Reduce the threshold of sodium and TRPV1 channels.
- Nociceptors fire more easily, leading to hypersensitivity
What is the mechanism of action of bradykinin in nociceptor sensitisation?
- Bradykinin binds to its metabotropic G protein-coupled receptor on the nociceptor
- Protein kinases are activated within the neuron
- Phosphorylation occurs on the TRPV1 channel, making it more sensitive
What is the result of bradykinin’s action on the TRPV1 channel?
The TRPV1 channel becomes more sensitive, firing at lower temperatures
What is the role of first-order neurons in the spinothalamic tract?
First-order neurons (nociceptors) detect pain at the site of injury (skin, muscles, organs) and send signals to the spinal cord via the dorsal horn
What happens to first-order neurons once they enter the spinal cord? (spinothalamic tract – pain)
- Their fibres travel through the tract of Lissauer.
- They synapse in the substantia gelatinosa (lamina I and II).
- Glutamate and substance P are released to excite second-order neurons.
Where are second-order neurons located, and what is their function? (spinothalamic tract)
Second-order neurons are in the dorsal horn of the spinal cord:
- Cross to the opposite side of the spinal cord.
- Ascend to the thalamus through the anterolateral column.
What is the role of third-order neurons in the spinothalamic tract?
- Sensory component: Project to the primary somatosensory cortex to encode location and modality of pain.
- Emotional component: Project to the insula and cingulate cortex (limbic system, prefrontal cortex) to encode emotional responses to pain.
Why does referred pain happen?
Visceral nociceptors and skin nociceptors converge on the same second-order neurons in the spinal cord, leading the brain to misinterpret the source of pain
What is referred pain?
Referred pain occurs when the brain misinterprets visceral pain (from organs) as coming from the skin or muscles
What is an example of referred pain?
In angina (heart pain), the pain is perceived in the left arm or upper chest because the brain receives signals from both the heart and these skin areas through the same spinal neurons
What is stress-induced analgesia?
the body’s ability to temporarily reduce pain during stressful or dangerous situations, allowing for survival or focus on a demanding task
How does the body achieve stress-induced analgesia?
- The brain activates a descending modulatory system to reduce pain signals travelling from the body to the brain.
- Higher cortical regions initiate these pathways to suppress pain
What role does the periaqueductal grey matter (PAG) play in pain regulation?
The PAG initiates pain suppression by activating descending modulatory pathways
What is the function of the rostral ventromedial medulla (RVM)?
The RVM sends inhibitory or excitatory signals down the spinal cord to modulate pain in the spinothalamic tract
Outline the pathway of pain modulation
- Cortical regions trigger the pathway and send signals to the PAG.
- PAG sends signals to the RVM.
- RVM sends modulatory signals to the dorsal horn where pain is inhibited or amplified
What is the order of regions in the descending pain modulation pathway?
Cortical regions → PAG → RVM → Dorsal horn
How does the inhibition of pain occur in the dorsal horn?
- The PAG activates serotonergic neurons in the RVM.
- These neurons excite inhibitory interneurons in the dorsal horn.
- Inhibitory interneurons release neurotransmitters that reduce spinothalamic tract activity, blocking pain signals.
What is the result of pain inhibition in the dorsal horn?
Pain signals from nociceptors are blocked, resulting in fewer pain signals traveling to the brain.
What are the opioid peptides used by the body to inhibit pain?
Endorphins and enkephalins.
How do opioids inhibit pain?
- Opioids bind to inhibitory metabotropic receptors.
- This reduces the activity of neurons and blocks pain signals
What is the role of opioids in the PAG and RVM?
- Opioids inhibit inhibitory interneurons that normally suppress the pain pathway.
- Result: The pain inhibition pathway remains active.
How do opioids act in the dorsal horn to inhibit pain?
Opioids act directly on second-order neurons, preventing them from transmitting pain signals to the brain
What is the overall effect of the endogenous opioid system?
The endogenous opioid system reduces or blocks the transmission of pain signals along the pain pathway
What are opioids
Opioids are drugs used for pain relief.
how do opioids work?
they work by binding to specific opioid receptors in the brain, which reduces pain perception and creates a sense of calm.
What is Naloxone
an opioid antagonist that binds to opioid receptors without activating them displacing opioids.
why is Naloxone useful?
It reverses opioid effects and can treat opioid overdose by displacing opioids from receptors
what are examples of opioids for severe pain and mild pain?
Morphine (for severe pain) and codeine (for mild pain).
What are semi-synthetic opioids
chemically modified versions of naturally occurring opioids
What are examples of semi-synthetic opioids
heroin
What are synthetic opioids and what are some examples?
- completely man-made
- Fentanyl
When are synthetic opioids used for
severe pain
What are the risks associated with opioid use?
- Dependency: Physical and psychological reliance.
- Tolerance: Need for higher doses over time to achieve the same effect.
- Overdose: Potentially fatal respiratory depression
What does PCA stand for, and how is it administered?
- Patient-Controlled Analgesia
- it allows patients to self-administer pain relief using an IV pump
How does an infusion differ from PCA?
An infusion delivers medication continuously through an IV line, while PCA allows self-administration on demand.
What is intramuscular administration?
It involves injecting medication directly into a muscle.
How are oral medications administered, and what is a key characteristic of this method?
- by mouth;
- it is convenient but slower due to the digestive process
Where are medications delivered in epidural/spinal administration, and what is it commonly used for?
- injected into the epidural space or spinal fluid
- commonly for regional pain relief during childbirth or surgery
Where in the brain are opioid receptors that play a role in pain transmission located?
In the pons and midbrain
What is the function of the periaqueductal grey matter, and where is it located?
- in the midbrain
- crucial for pain suppression and is a key site for opioid action
What is the role of the nucleus raphe magnus in pain modulation?
It inhibits pain signals as they ascend to the brain
Why can opioids cause constipation?
Opioid receptors in the gastrointestinal tract affect digestive processes, often leading to constipation
How do peripheral opioid receptors influence pain and inflammation?
They act locally in peripheral tissues to modulate pain and inflammation.
What is the primary function of MU receptors?
They are the primary opioid receptors (e.g., morphine) responsible for powerful pain relief (analgesia) but also cause side effects like nausea and itching.
What role do delta receptors play in pain and mood?
involved in pain modulation and emotional responses, influencing mood and the emotional aspects of pain
What is the key benefit and limitation of kappa receptors?
provide pain relief with fewer side effects, like respiratory depression, but can cause dysphoria instead of euphoria, limiting addiction potential
To which type of receptor does morphine bind, and what is the effect?
Morphine binds to MU receptors in the brain and spinal cord to reduce the perception of pain
What are the common side effects of morphine?
Respiratory depression, nausea, vomiting, constipation
Why can morphine cause respiratory depression?
It slows down breathing, which can be dangerous at high doses.
How does morphine affect the gastrointestinal tract?
It slows down movement, leading to constipation.
Against which specific opioid side effect is naloxone most effective?
Respiratory depression
What does the acronym ABC stand for when managing a patient?
Airway, Breathing, and Circulation.
Why is checking the airway a critical first step?
To ensure it is clear, as an obstructed airway prevents oxygen from reaching the lungs.
What does assessing breathing ensure?
That the lungs are ventilating properly and oxygen is reaching the blood.
Why is checking circulation important in patient care?
To ensure that blood is carrying oxygen properly to tissues
What can happen when a patient regains consciousness rapidly after naloxone administration?
They may wake up quickly and agitated as they regain consciousness
Why is close monitoring required after naloxone administration?
Its short duration means opioid effects can return once naloxone wears off, causing the patient to collapse suddenly.
What is ketamine primarily used for?
It is a fast-acting anesthetic and analgesic used for pain relief and sedation
How does ketamine reduce pain?
It blocks NMDA receptors in the brain, reducing pain signals, and interacts with kappa and delta receptors for additional pain relief
What makes ketamine a suitable anesthetic for patients with low blood pressure?
Its sympathomimetic effect increases heart rate and blood pressure.
What is emergence phenomena in patients recovering from ketamine?
Vivid dreams or hallucinations experienced as the patient wakes up.
What are the three main properties of NSAIDs?
Analgesic (pain relief), antipyretic (fever reduction), and anti-inflammatory.
How do NSAIDs work to reduce pain and inflammation?
By inhibiting the Cyclooxygenase (COX-1 and COX-2) enzymes.
What are common side effects of NSAIDs on the gastrointestinal system?
Gastric irritation
How can NSAIDs affect the respiratory system in some patients?
They can cause bronchospasm, leading to breathing difficulties.
How does aspirin, a type of NSAID, affect blood clotting?
It inhibits platelet function, reducing the ability of blood to clot.
What enzymes does aspirin inhibit to reduce pain, fever, and inflammation?
Cyclooxygenase (COX) enzymes
How can high doses of aspirin affect cellular energy production?
It disrupts oxidative phosphorylation
What is “air hunger,” and how is it related to aspirin?
Difficulty breathing caused by excessive aspirin intake.
What are paracetamol’s primary uses?
Pain and fever relief.
What is the main risk of paracetamol overdose?
liver damage
How do anxiolytics help with pain management?
They reduce anxiety, which can indirectly lower pain perception
What is the role of local anesthetics in pain management?
They block pain at the nerve level for specific procedures
Which types of medications, like gabapentin, are used for chronic pain?
Antidepressants and antiepileptics.
How does ether stimulate the cardiovascular system?
stimulates the sympathetic nervous system, helping maintain cardiovascular stability, especially in cases of severe blood loss
Why is ether’s high blood/gas partition coefficient a challenge in anesthesia?
It causes slow uptake into the blood, making it difficult to achieve and maintain an appropriate anesthetic depth.
What is the primary purpose of anti-emetic drugs?
To prevent nausea and vomiting, especially as a side effect of anesthesia.
Name three additional anti-emetics used based on patient needs.
Steroids, prochlorperazine, and cannabinoids
Name three common benzodiazepines
Midazolam, Diazepam, Lorazepam.
What are the routes of administration for benzodiazepines?
Oral, Intravenous, Intramuscular.
What are the risks of over-sedation with benzodiazepines?
Impaired awareness and responsiveness, loss of airway reflexes, and respiratory depression, especially when combined with other sedatives
What is the reversal agent for benzodiazepine overdose?
Flumazenil, which blocks benzodiazepine effects
What is the primary difference between amides and esters in local anesthetics?
Amides have a longer duration of action and are broken down more slowly, while esters have a shorter duration and are metabolized quickly
Give three examples of amide local anesthetics.
Lignocaine (lidocaine), prilocaine, bupivacaine
What is the primary target of local anesthetics in nerve cells?
Sodium channels.
Describe the first step in the mechanism of action for local anesthetics.
The un-ionized drug crosses the cell membrane into the inside of the nerve cell.
What happens to the drug once it is inside the nerve cell?
It becomes ionized, enabling it to block sodium channels.
What is the ultimate effect of local anesthetics blocking sodium channels?
Inhibition of action potentials, preventing pain signals from traveling to the brain.
Why is there a toxicity risk with local anesthetics?
Blood vessels and nerves are closely associated, increasing the chance of accidental vascular injection.
