Pain systems (+temperature) Flashcards
What would be a difference between mechanosensory pathway and pain/temperature pathway?
Pain/temperature
- starts with free nerve endings
- Makes a connection to the second order neuron already in the dorsal horn of the spinal cord -> crosses over
What are the receptors of pain/temperature? What are its 2 classes - sensitive to, how big -> result?
- Free nerve endings -> branching under skin
- Among the smallest fibers of receptors
- Two classes:
- Ad (delta) fibers
- axons of receptors for nociceptions
- some also sensitive to thermal and mechanical energy that could threaten the tissue
- lightly myelinated => greater conduction velocity - C fibers
- (almost) unmyelinated
- respond to multiple modalities that could result in damage e.g. thermal, chemical
- Ad (delta) fibers
What kind of receptor channels does this system use? How do they work?
= transient receptor potential ion channels (TRIP channels)
- different could be sensitive to various sensory info e.g. cold, acidic
- plus modulatory binding spots for chemical compounds e.g. capsaicin
=> allow passage of Na+ (voltage change) and Ca2+ (digestive change)
How do C and Ad fibers innervate the spinal cord?
- Dorsal horn - lamina 2
= sunstantia gelatinosa
- populated by small cell bodies
- projection- and inter- neurons that receive
signals form the first order neurons
- C fibers
= mediator of pain signals - We have some additional cells in lamina 5 and 6
- innervated by Ad fibers
What’s the difference between first and second pain? Feeling, velocity, pathway, end product?
- First pain - sharp-shooting pain, rapidly gone
- Ad fibers -> thalamus (ventral posterior) -> somatic sensory cortex (= localization of injury)
= Spinothalamic tract
- Ad fibers -> thalamus (ventral posterior) -> somatic sensory cortex (= localization of injury)
- Second pain - throbbing
- C fibers -> Brainstem (-> will have widespread effects) &thalamus (medial nuclei - more cognition) -> ventral-medial forebrain (= affective reaction)
What structures could be reached via the second pain pathway?
Reticular formation - system of nuclei
- may influence overall level of arousal and attention => based on pain it modulates our cognition
Periaquaductal gray
- feedback modulation of pain sensation
Insula
- building image of our body based on the internal state
ACC
- evaluation of significance or consequences of our actions
What is hyperalgesia? What causes it - explain the interaction?
What other phenomenon (extreme) may occur form this?
= enhanced sensitiviry to mechanosensory stimulation -> inflammatory pain
- Following tissue injury -> immune system -> these cells infiltrate the area e.g. macrophage -> release immune mediators e.g. histamine => affects vascular response, first order nociceptor axons
-> free nerve ending may release substance themselves e.g. substance p
=> increased responses of nociceptor neurons
- Allodynia = normally innocuous stimulus might be perceived as being painful
What is wind up and central sensitivity? What causes it?
- Wind up = repeated activation of nociceptors leads to sustained depolarization of second order neuron
- if mediated by NMDA => LTP => Central sensitivity - There could also be changes of gene expression -> long-term alteration
What is Analgesia? What else can have similar impact?
= loss of perception of pain
- context, distruction, culture (=descending modulation)
Describe the descending pathways that modulate pain.
- Key: periaquaductal gray
= integrates signals and sends it to relevant structures - NE and SER can influence excitability of dorsal horn
How may e.g. Ralphe nuclei alter pain perception?
- Modulate excitability in the dorsal horn
- In dorsal horn we also have interneurons -> release neuropeptides e.g. encephalins -> inhibits activity of nociceptor neuron
What is the famous theory which would explain “scratching area around a wound to relieve pain”?
What potential circuit could explain this? How could we use it in future interventions?
- Gate theory of pain = in the CNS there may exist a competition between mechanosensory and pain sensation in which the mechanosensory may overtake the other
- In addition to normal connection (aBeta) in dorsal column there is a collateral that innervates interneurons in substantia gelatinosa -> inhibits transmission of pain => supresses firing of C fibers
=> Maybe next intervention could stimulate dorsal column
What kind of chronic pains could we encounter? What causes it (or theory)?
- Nociceptive CHP
- from ongoing stimulation of nociceptors
- may be due to inflammation
- involve both first and second pain
- from ongoing stimulation of nociceptors
- Chronic pain syndrome
- no known nociceptive etiology
- poorly understood e.g. maybe disregulation of feedback systems
- e.g. chronic lower back pain, fibromyalgia
- no known nociceptive etiology
What is meant by neuropathic pain? What causes it - in PNS (1) and CNS (3)?
= pain due to abnormal activity in nociceptive pathway that is unrelated to the presence of a nociceptive stimulus
- PNS = nerve compression (=> opening of channels)
- there may be abnormal somatic sensations
CNS
- sustained sensitization of neurons in nociceptive pathway
- abnormal activity in sympathetic outflow to visceral structures -> viscera than gives wrong info back to CNS
- maladaptive plasticity e.g. phantom limbs
Briefly elaborate on the anterolateral pathway of pain - from first to third order neurons.
- First order afferant neuron terminates in the dorsal horn (it actually also travels up and down)
- Start of anterolateral system -> second axon crosses the midline through anterior white commissure -> goes around the ventral horn and enter anterior lateral white matter -> sharp turn upwards
- Synapse in the ventral posterior lateral nuclei (not the same neurons as going from medial lemniscus)
-> 3rd order neuron send info to S1 = localization
Briefly explain how the info about pain from the FACE gets into the brain (i.e. spinal trigeminal tract)?
- Trigeminal root ganglion -> axon enters mid-pons -> turns down = spinal trigeminal tract
-> makes connections in spinal nucleus of trigeminal complex (diff axons terminate at diff places -> maps out the surfaces of the face)
-> second order n. across the midline
-> enters lateral tegmentum
-> superiorily into VPM thalamus
-> 3rd order neurons sending info into S1 specific for face
What would happen if there was a spinal injury to one side (just talking about sensory for now)?
=> damage to IPSElateral mechanoreceptive afferents
=> damage to CONTRAlateral nociceptive afferent
= dissociative sensory loss
- Plus zone of complete loss of sensation - due to damage to local dorsal ganglion cells
What’s interesting about the pathway of pain for viscera? What’s the clinical significance?
Apart from the regular contribution to anterolateral pain pathway - viscera can also signal as follows:
Dorsal root ganglion -> dorsal root -> synapses with neurons close to central cannal -> upward axon going through dorsal column -> synaptic connections to dorsal column nuclei -> going up -> VPL thalamus -> insular cortex (just like S1 for viscera)
- Patients with chronic pain -> small lesion in dorsal column -> improving quality of life
What are the referred pain patterns?
= notion that there may be some crossover between pain perception of viscera and mechanosensory pathway
- could happen in dorsal horn, dorsal column
Look at the lumbar spinal cord with dorsal roots highlighted.
Substantia gelatinosa
Where do the pain signals cross?
= ventral/anterior white commissure
Where do pain signals go after they crossed the midline?
Anterolateral white matter/system
Look at the trigeminal nerve entering mid-pons
Spinal Trigeminal tract
