Pain (me rn) Flashcards
Describe the structure and basic function of nociceptors
Arise from dorsal root ganglia
Unspecialised free nerve endings
A(delta), myelinated, 5 to 30 m/s OR C fibre unmyelinated axons <2 m/s (C fibres also do crude touch, temp, itch)
Discharge when strength of stimulus reaches high levels
Some are attached to thermoreceptors - activate at 43 degrees or below -17; also activated by capsaicin (from chili)
What types of pain are there?
(pain at having 0 time to practice for an exam you know you could do well in but philosophy fucked you up the arse)
First pain - sharp, acute; A(delta)
Second pain - diffuse, long lasting; C fibre
What are the types of A(delta) fibres?
Type 1 - mechano+chemical stimulation; high heat threshold
Type 2 - heat stimulation; high mechano-chemical threshold
What do C fibres respond to?
Thermal + mechano + chemical = polymodal
But also heterogeneous - some responding to 2/3+ types etc
Describe the properties of transient receptor potential channels and give some examples
VGK+ channels
6 transmembrane domains + pore = closed at rest; Na influx when active
Vanilloid receptor - TRPV1 - activated by capsaicin (from chili’s) + heat
TRPV4 - possible mechano-nociceptor
TRPA1 - chemical irritants including garlic and cigs (mmm)
What other receptors are there for pain?
Piezo2 + ASIC receptors - possible mechanoreceptors
ASIC3 = skeletal + cardiac muscle pain from to pH changes secondary to ischemia
What channel types are responsible for central pain transmission?
NaV1.7 - associated with pain disorders (mutations in the SCN9A gene that codes for the channel)
NAV1.7 - expressed in C fibre nociceptors
ONE OF THESE IS MEANT TO BE 1.8 NEEDS CHECKING
What is the tract that carries pain information before decussation in the spinal cord called and what is its path?
Dorsolateral tract of Lissauer (fuck off)
Dorsal horn - up/down 1-2 spinal cord segments - penetrate grey matter of Rexed’s laminae I, II and V
Then become 2nd order neurons from I + V that ascend two spinal levels before decussating and ascending further to the brainstem/thalamus in the spinothalamic/anterolateral tracts
Where do A(delta) and C fibres terminate?
A(delta) - I + V
C - exclusively in Rexed’s laminae I and II
Where do A(beta) fibres terminate?
Non-nociceptive fibres
Rexed’s laminae III, IV, V
Some lamina V neurons have nociceptive and non = multimodal = wide-dynamic-range neurons = likely substrates for referred pain
What information about the type of pain is the spinothalamic tract responsible for conveying?
Sensory-discriminative - Location, intensity, quality
From all modalities of pain
Relayed through fibres from the ventral posterior nucleus (VPL) to the somatosensory cortex
How does the affective-motivational aspect of pain get conveyed?
Feeling of fear/anxiety; autonomic activation etc
Anterolateral system transmits to: reticular formation + periaquductal gray + superior colliculus + parabrachial nucleus (then to: hypothalamuus, amygdala, anterior cingulate cortex and insula) + medial thalamic nuclei (then to hypothalamus + anterior cingulate and insula)
Anterior cingulate = key in the ‘unpleasantness’ aspect of pain
What is the pain matrix?
(what I’m living in rn, Jesus save me…)
The widespread involvement of neural structures involved in pain perception that explains the sensory, motor, affective and cognitive effects of pain
How are noxious stimuli transmitted in the head and neck?
Trigeminal pathway
1st order neurons branches from CN V, VII, IX and X - medulla (in the spinal trigeminal tract) - spinal trigeminal nucleus (split into pars interpolaris + pars caudalis) - 2nd order neurons progress to various brainstem and thalamic targets such as the contralateral VPM and then on to the somatosensory cortex (for the sensory discriminative) + reticular formation etc (for the affective-motivational)
What is the hypothesised general function of Rexed’s laminae I?
Responsible for interoception ie low level integration of information that represents the physiological condition of the body which when neurons ascend to higher levels, is responsible for the homeostatic control of functions (sweating etc)
What is hyperalgesia?
Upon tissue damage, mildly noxious stimuli
elicit a significant pain response (to prevent further damage + attract healing/anti infection factors)
What is peripheral sensitisation?
Nociceptor + inflammatory mediators release from active injury
What are some examples of inflammatory mediators?
Neuronally mediated - substance P, calcitonin gene-related peptide (CGRP), ATP (all increase vasodilation and histamine release from mast cells)
Non-neuronal - mast cells, platelets, basophils, macrophages, neutrophils, endothelial cells, keratinocytes, fibroblasts - release H+, arachadonic acid, bradykinin, serotonin, prostaglandins, nerve growth factor, cyotkines (interlukin-1beta and TNF-alpha)
Most of these substances alter nociceptor fibre ion channels
(what a list wow)
How do prostaglandins contribute to peripheral sensitisation?
Bind to GPCRs - increase cAMP in nociceptors
Decrease depolarisation threshold - phosphorylate TTX-resistant Na channels in nociceptors (like do i give a fuck)
How do NSAIDs work? (should know this)
Irreversibly (only aspirin) inhibit COX1 - inhibit prostaglandin synthesis
MEDICINE BITCHES SUCK A DICK
What is central sensitisation?
Due to increased excitation of dorsal horn neurons secondary to activation of nociceptor afferents, which are now able to generate action potentials in dorsal horn neurons = increased pain sensitivity
Thus these 2nd order neurons can also respond to normally innocuous stimuli and generate a central pain response (allodynia) - this can outlast the initial pain of the event by several hrs
What is windup?
Progressive increase in the rate of discharge of dorsal horn neurons in response to repeated low frequency activation of nociceptive afferents
Arises from the summation of potentials evoked in dorsal horn neurons by nociceptive inputs and the sustained depolarisation of these neurons through opening of L-type Ca channels + removal of Mg2+ block from NMDA receptors - increasing sensitivity to Glu = the neurotransmitter used in nociceptive afferents
What other mechanisms exist for central sensitisation?
NMDA receptor mediated elevations of CA2+ in post synaptic spinal cord neurons
Reduction in GABAergic and glycineric spinal cord inhibition, possibly secondary to K+Cl- cotransporter dysfunction
Role for astrocytes and microglia (especially in nerve injury/arthritis/chemo and cancer)
What is the role of the periaqueductal gray?
Pain modulation - stimulation in rats produces behavioural analgesic effects and inhibits activity of nociceptive projection in the dorsal horn; also mediated by parabrachial nucleus, dorsal raphe, locus coeruleus and medullary reticular formation and the neurotransmitters 5HT, DA, ACh and histamine
What is the Melzack-Wall gate theory of pain?
Pain is modulated by descending pain fibres as well as concomitant activation of the painful area with low threshold mechanoreceptors ie rub your head if you bump it, it will confuse your pain matrix and everything will be rosy
What are endogenous opioids?
Enkephalins, endorphins, dynorphins
Responsible for pain modulation (in the areas mentioned as well as dorsal horn neurons) + their receptors is why we like to do skag init
What are endocannabinoids?
Mans best friends.
(Also responsible for the selective suppression of nociceptive neurons via CB1 receptors in the dorsal horn of the spinal cord; centrally they decrease GABA and glutamate and modulate neuronal excitability; act on microglia by CB2 receptors)
