Physiology of Pain Flashcards
What are nociceptors + where is their cell body? Where do they enter and make synapses?
Nociceptors enter the spinal cord, their cell body is in the dorsal root ganglion.
Nociceptors make synapses within the dorsal lateral horn in laminae I, II and V
They also make synapses w secondary afferents which carry signal to the brainstem.
There are 2 broad classes of nociceptors - compare A delta vs C fibres
structure of fibre, what they respond to, where they synapse + pathways, what they cause + release
Aδ fibres: Thin, myelinated = fast, gives sharp stab feeling from mechanical trauma or noxious heat
Synapse in SC using glutamate w secondary afferents
Cross over at midline and travel up anterolateral spinal tract–> thalamus and relayed to cortex.
C fibres: Thin, unmyelinated, slower
Respond to mechanical trauma, temp, inflammation
C fibres cause long throbbing ache, not sudden like A delta.
Release glutamate and sub P
Imagine you are walking on the beach and step foot in a shard of glass. Explain the signals that occur and the neural pathways
Glass=noxious stimulus that activates Aδ
The signal is sent to SC where it produces protective withdrawal reflexes, eg leg will flex.
Signals also sent to cerebral cortex, (conscious perception) =first stab of pain
C fibres are activated in the cerebral cortex and inflammation starts
Describe the somatosensory pathway for touch
Touch receptor afferent ascends up dorsal column in SC –> decussates in medulla - Ascends in medial lemniscus to thalamus (VPN) –> internal capsule to PSSC
How is the primary somatosensory cortex involved in pain perception?
PSC: discriminates and localises pain
If electrically stimulate region of cortex for ring finger = pins and needles here, meaning you’re activating nociceptor pathways
What would happen if someone had a stroke in this region of their PSC?
Stroke wiped out part of SSC for arm and hand: lost ability to discriminate, localise and describe noxious stimuli
Even though he could not localise the pain he still found it unpleasant bc frontal lobe and medial pain pathways still operating= emotional response to pain
Notice that the PSC has no region specific for the heart. Why do people feel pain when experiencing a heart attack?
Nociceptors from viscera enter SC and piggyback on the pathways belonging to somatic system e.g. heart pain:
C7-T5 = left upper limb and activates medial aspect of SSC = converted into sensation in left upper limb
Compare lateral vs medial pain pathways
Lateral: Nociceptor afferents–> decussate in dorsal horn - go up anterolateral spinal tract + synapses in vpn - then ascends via internal capsule to the PSSC
This pathway= for pain perception and sensation
Medial: Nociceptor afferents–> decussate in dorsal horn - go up anterolateral spinal tract - then axons make multiple connections in brain stem + terminate in midline thalamic nuclei. Axons then project into insular (homeostasis) + ant.cingulate cortex (emotion)
This pathway= distress, fear, protective behaviours, increases alert + fight or flight
How is the medial pain pathway associated with more emotion?
Nociceptor afferents in the medial pathways project into ant.cingulate cortex which connects w hypothalamus, amygdala and frontal cortex.
Therefore medial pain pathway inc emotional, homeostatic responses = beyond sensory aspects
What happens if you stimulate midline non specific thalamic nuclei?
If you stimulate midline non-specific thalamic nuclei: people can’t localise sensation but they don’t like it
Patients with primary SSC lesions could not describe or localise any sensation from noxious stimulus but he found it unpleasant
inflammation is vital for healing and hence an aspect of “normal” pain. What 2 things can it cause following injury?
hyperalgesia (increased pain from painful stimuli)
allodynia (non-painful stimuli become painful)
Describe how nociceptors respond to inflammation and 2 ways this can lead to hyperalgesia and allodynia
Trauma+inflammation depolarises c fibre endings
Inflammation also hypersensitises nociceptor endings so they depolarise more easily
Moreover, C fibres release peptides from their sensitive endings which act as i. mediators = positive feedback bc inflammation increases activity of neighbouring C fibres –> spreads pain out of tissue = hyperalgesia and allodynia
in circumstances where survival = paramount, pain can be subconsciously switched off as they would hinder your survival.
Describe stress induced analgesia using the descending modulation pathway.
The OFC + ant.cingulate cortex send signals to the periaqueductal grey in midbrain –> raphe magnus nucleus + locus coerulus - releases serotonin + NA (alpha 2)
Serotonin + NA act as inhibitory interneurons, decreasing secondary afferent activity in SC –> entire pain pathway doesnt work!
3 ways opioids cause analgesia? What 3 other methods can cause analgesia?
Opioids/morphine act on periaqueductal grey + OFC to switch off pain
Opioids also act in spinal cord - mimicking inhibitory interneurons that are normally activated by NA + serotonin
Placebos, coping strategies and CBT also induces the analgesic pathway
What is anxiety induced hyperalgesia?
Using this concept how can you decrease pain and chronic pain?
what else in these pathways can cause pain?
Underactivity in orbitofrontal and anterior cingulate cortex amplifies pain - in anxiety or those w poor coping
Hence improving mood and coping ability decreases pain
An example of this= chronic pain due to depression: antidepressants will also increase transmission in descending anti-nociceptive pathways
Also, a physical pathology in these pathways = pain, may explain migraines
Describe the peripheral issue that arises in poorly controlled T2DM patients
Poorly controlled T2DM patients have microscopic tissue + nociceptor damage as glucose binds to proteins
Damaged nociceptors fire inappropriate ap’s, leading to pain/inflammation build up = hyperalgesia and allodynia
At this point, it is a peripheral problem.
What is diabetic neuropathy?
In diabetic neuropathy, nociceptors activated by tissue damage produce abnormal activity= continued pain sensation
Damaged sensory receptors peripherally start to die + feet also become numb.
Describe the activity of nociceptor fibres in the laminae and describe the difference for lamina V. + what can suppress these pathways?
ADelta and C fibres enter SC + make connections in lamina I, II, V
Layer V gets both pain fibres AND ordinary touch receptor input which makes connections in laminar 4.
Touch receptors drive these cells to low firing frequency - however nociceptors drive high firing frequency = So brain interprets this as either touch or injury!
Inhibitory GABA, opioids suppress these pathways
People with chronic pain are also treated with benzodiazepines and anticonvulsants. What are these and why are they used?
(what are anticonvulsants normally used for + compare this to their MOA in treating chronic pain)
Chronic pain is sometimes treated w benzodiazepines normally used for anxiety - they are GABA agonists, increasing GABAergic inhibition e.g spinal cord inhibition
Anticonvulsants are normally used to block high Hz AP firing during seizures, but they also reduce activity at synapses that have undergone long term potentiation (reducing chronic pain)
Changes in the normal pain circuit may trigger neurogenic pain. Describe 4 ways this can happen
Descending control problems/ imbalance causes chronic pain
Dysfunction/downreg of Spinal Inhibitory Systems
Long-term potentiation of excitatory synapses - occur after injury discharges (trauma to nerve) OR persistent activation (diabetic neuropathy)
Central sensitisation: chronic pro-LTP peptide release from C fibres, generation of i.mediators, abnormal glial activity - this is seen in SC in chronic peripheral injury
