Module 26 - Neurophysiology of PAIN Flashcards
What are the two types of pain?
- Acute pain
- Chronic
What is acute pain and its function?
- Clearly defined stimulus
- Stimulus determines the intensity & duration of pain
- Localized receptors (afferents) are affected
- Function:
- Detect tissue damage or impending damage; initiate avoidance reaction
What is chronic pain?
- Persistence of pain, often in absence of obvious stimulus
- Can be in absence of any physiological disruption
- Cause & mechanisms are largely unknown
- Difficult to treat
- Often involves changes in pain pathways (neural plasticity)
- Can result in a multitude of negative consequences
What are some pathological examples of chronic pain?
- Deafferentation pain (phantom limb pain)
- Neuropathic pain
- Thalamic pain
- Trigeminal neuralgia
What are some similarities between free nerve endings (nociception) and mechanoreceptors (sensation)?
- Transduce a variety of stimuli into receptor potentials → trigger action potentials
- Frequency (rate) coding:
- Increase stimulus intensity = increase depolarization of receptors and increase the firing rate of pain (nociceptive) afferents
- This means the sensation of pain is increased
- There are no obvious morphological differences between receptors.
What are some differences between free nerve endings and mechanoreceptors?
- These nerve endings only respond to painful stimuli = they are specialized for damaging/nociceptive stimulation. → there are different transduction mechanisms that respond to different stimuli
- Channel transduction mechanism on certain nociceptors → Pore is normally closed - in response to the presence of stimuli on the surface of the cell, the pore opens allowing NA+ (and Ca2+) to flow, resulting in an AP
- Information travels much more slowly
- Fast pain vs slow pain
- Localization is relatively poor
- Due to widespread branching of afferents in the skin
- Repeated or prolonged stimulation often leads to a stronger response (sensitization), rather than adaptation
- ***Referred pain
***Pain is both mechanical and affective (amygdala for example)
- ***Referred pain
There is a wide variety of nociceptors. What are the two types of nociceptors and their corresponding subdivisions?
- Specific to one type of stimulus
- Mechano-nociceptors (intense force)
- Thermo-nociceptors (distinct from thermoreceptors)
- Heat nociceptors (> 45 degrees)
- Cold nociceptors (< 5 degrees)
- Chemo-nociceptors (Bradykinin, Histamine, H+, ATP, prostaglandins)
- Non-specific (response to more than one stimulus)
- Polymodal (poly = several) nociceptors
- force, temperature, and chemicals
- Polymodal (poly = several) nociceptors
How does a nociceptor differ in their travel time to respond to different stimuli to regular mechanoreceptors (basic touch)?
- A beta afferent (mechanoreceptors = touch) → heavily myelinated = 35-75 m/s
- FAST (sharp) → A delta → myelinated = 5-30 m/s (compared to touch sensation = slow)
- SLOW (dull, burning) → C fibers → unmyelinated = <2 m/s (compared to touch sensation = slower)
- ***Both of the two types of pain are still slower than the mechanoreceptors for touch
What type of receptive field is responsible for nociception?
It is a large receptive field, therefore we can’t give accurate information about where the stimulus is within its field. The “size” of the receptive field depends on how widespread the branching of its terminals are
Is painful sensation simply just excessive stimulation of mechano (touch) receptors? Yes or No? Explain.
- The perception of pain (nociception) depends on specifically dedicated receptors and pathways
- NOT excessive stimulation of the same receptors that generate other somatic sensations
Describe/draw the route of the spinothalamic pathway.
- Axons enter the spinal cord from the spinal ganglion and travel up or down 1-2 segments within Lissauer’s tract before synapsing with secondary neurons in the substantia gelatinosa of the posterior horn. Secondary neurons then cross over to the contralateral side via the anterior white commissure.
- Caudal medulla = in the caudal medulla, the spinothalamic tract of the anterolateral system lies adjacent to the pyramids, which contain the corticospinal tracts
- Rostral medulla = in the rostral medulla, the spinothalamic tract lies between the inferior olivary nucleus and the nucleus of the spinal tract of the trigeminal nerve.
- Pons = in the pons, the spinothalamic tract lies just lateral to the medial lemniscus of the posterior column-medial lemniscus ascending tract.
- Midbrain = in the midbrain, the spinothalamic tract lies just posterior to (and can appear somewhat continuous with) the remedial lemniscus of the posterior column-medial lemniscus ascending tract.
- Thalamus = the spinothalamic tract terminates in the VPL nucleus of the thalamus.
- From there, fibers project through the internal capsule and corona radiate to terminate in the primary somatosensory cortex.
What is the blood supply to the PCML pathway?
The anterior spinal artery supplies the anterior ⅔ of the spinal cord, which includes the anterolateral system.
Once the pain stimulus in the dorsal horn, where do the axons give off branches?
- Axons give off branches which synapse with 2nd order neurons
- Lamina I (marginal zone) → A-delta and C fiber input primarily
- Lamina II (substantia gelatinosa) → C fiber input primarily
- Lamina V (base of dorsal horn) → A-delta
What is referred pain? Give an example.
Very few neurons in the dorsal horn of the spinal cord are specialized for transmission of visceral (internal) pain (all coming from the skin/ none are specific for the visceral organs) → it comes from lamina V in the dorsal horn.
- We recognize visceral pain, but it is conveyed centrally via dorsal horn nervous that are also concerned with cutaneous pain.
- As a result of this, we know that visceral pain is often felt or referred to the skin, due to overlapping dermatomes.
- Sometimes the disorder or an internal organ is perceived as a cutaneous pain
- Angina (poorly perfused heart muscle) → there will be convergence onto relay pain neuron
- A heart attack pain is often described at a burning pain down the left side of the arm, because the visceral afferent comes into the dorsal horn at the same place as the information from this dermatome. (Rex lamina V!!!!)
What are the two aspects of pain and their general concept?
- Sensory discriminative = qualitative aspect of pain = burning, stabbing, dull, ache, etc.
- Affective motivational = Negative feelings, scared, the emotional component of pain, etc.
What is the concept of sensory discriminative of pain?
- It is known to be processed in the ventral posterior lateral nucleus of the thalamus
- It is the location, intensity and quality of the pain.
What is the concept of the affective motivational part of pain?
- It is the unpleasantness of pain
- The fear and anxiety
- The autonomic activation (fight or flight)
What is the gate control theory of pain?
- It is the ascending pain suppression model
- If we activate the mechanoreceptors that are usually used to detect tactile sensation, this can override the information coming from noxious stimuli. They activate interneurons (for example in the substantia gelatinosa) and stops the flow of transmission of the nociceptive endings.
- This is why pain control can work with a TENS machine. The basis of why rubbing and scratching can reduce pain
What are the endogenous opioids (descending control) pain control theory? What are the three main types of endogenous opioids?
- The endogenous opioids which are present in the periaqueductal gray (PAG) can descend be effective in the dorsal horn of the spinal cord. A lot of it comes from the Raphe nuclei (look at image on the right for more detail)
- Enkephalins
- Endorphins
- Dynorphins
- Example - enkephalin release in dorsal horn = descending input excites local circuit neuron resulting in the release of enkephalin onto the nociceptive terminal
- It inhibits the release of neurotransmitter, decrease signal sent to higher centers in the CNS
- This response is NOT sensory discriminative!!!!!
- ***It is why morphine is effective for pain relief → it also has an effect on the amygdala = the emotional concept of pain. Often patients will say that they still feel the pain but they simply do not care about it anymore. Therefore, this opioid does not stop the actual sensation of pain, it is just turning off us caring about the pain. It is why it is so highly addictive.
What is the main idea of the mechanism of allodynia?
- Malformation in the neurons may lead to non-nociceptive fibers stimulating second-order neurons - causing inappropriate pain sensation known as allodynia
- Both touch (A-beta) and pain (A-delta) fibers carry information to the dorsal horn. → it is the reason why allodynia can occur
What is the mechanism of peripheral sensitization?
Interaction of nociceptors with “inflammatory soup” of substances released due to tissue damage
The steps:
- Nociceptors release peptides and NTs (eg. substance P)
- This causes vasodilation, swelling, histamine release
- Non-neuronal cells augment the inflammatory process
What ends up happening is the site of damage is surrounded with inflammation/swelling/vasodilation → hyperalgesia = the surrounding skin with flare
Hyperalgesia & allodynia ???
Hyperalgesia & allodynia (painful sensation to non-painful stimuli) outside of zone terminal branching (of nociceptors) - not due to peripheral mechanisms - must be centrally mediated
What is the synaptic plasticity that happens with allodynia/central sensitization?
Image
