Flashcards in Pain Deck (43):
what is pain and why is it needed?
Pain is an unpleasant sensory and emotional experience with actual or potential tissue damage
why is pain needed?
because it is a signal to alert organism to potentially injurious situations (both acute and chronic)
what does signal in pain encode?
signal encodes the 1. nature and 2. location of the painful stimulus
what are the different type of pain perception?
burning, stinging, aching, itching, plucking
wha are the different mode of painful stimuli?
3. mechanical (being kicked, pin prick)
4. chemical (acid, wasp sting, capsaicin, lactate and smelling salts)
what are the seven types of pain?
1. visceral pain
2. inflammatory pain
3. neuropathic pain
4. cancer pain
5. post-operative pain
6. migraine/ headache
7. cutaneous pain
what are the common site of painful stimuli?
DUBS JR CTM
1. digestive system
2. urinogenital system
3. brain meninges
4. skin (cutaneous)
6. respiratory system (irritants, stretch)
7. cornea (v. dense sensory innervation)
9. muscle (exercise, post exercise, trauma)
what are the FOUR sensory pathways for transmission and processing of pain signals?
1. peripheral stimulation/sensitisation
2. pain transduction and conduction
3. pain transmission and processing
4. pain perception/central sensitisation
what are afferent neurons?
afferent neurons or sensor neurons are the neurons/ pathways that carry signals from the body to the CNS (brain + SC)
what are primary afferents?
the sensory neurons (axons or nerve fibres) in PNS that transduce information about mechanical, thermal and chemical states of body and transmit it sites in the CNS
All primary afferents convey pain related signals?
B. False, not all
what are primary afferent nociceptors?
the primary afferents/ sensory neurons that carry pain signals are called primary afferent nociceptors
the activation of nociceptors results in
A. acute pain
B. chronic pain
A. acute pain
what is the physiology of primary afferent nociceptors?
small sized and slowly conducting neurons (the size is directly proportional to conductance speed)
name TWO places where nociceptors can be easily found?
which TWO types of fibres are mainly present in nociceptive neurons of skin?
1. c fibres
2. a-delta fibres
draw the ascending circuit of pain
show consists of
1. periphery - ganglion + a-delta and c nociceptors
2. spinal cord - innervation of those nociceptors
3. brain - acting on thalamus, hypothalamus, medulla/brain stem and exchange b/w thalamus and cortex
what is the difference b/w a-delta and c fibres on the basis of
3. conduction velocity
4. sensory receptors present
1. diameter (A-delta>C)
A-delta - 1-5 micrometre
C - 0.2-1.5 micrometre
A-delta - myelinated
C - non-myelinated
3. conduction velocity (m/s) (A-delta>C)
A-delta - 3-30
C - 0.5-2.0
4. sensory receptors
A-delta - mechanoceptors + thermoceptors + nociceptors
C - thermoceptors + nociceptors
what are the THREE types of A fibres?
to what kind of stimulus do nociceptors respond to?
they respond to noxious stimulus, the stimulus that a re capable of priding a tissue damage
what does signalling pathway consist of?
- consists of periphery, cell body and dorsal horn of SC
- the periphery is the detector with specialised sensory endings that sense the various type pain stimuli
- the dorsal horn is the communicator which has pre-synaptic terminal
how does detector trigger communicator function?
- enough pain stimuli at the membrane -> depolarisation -> AP fired -> travels and divide into 2 AP at the cell body
- one AP goes to the cell body and the other to the pre-synaptic terminal
what mocleules do the sensory ending and pre-synaptic terminal consist of?
- Periphery sensory ending - ion channels + peptide transmitter vesicle + receptors
- dorsal horn of SC pre-synaptic terminal - ion channels + peptide transmitter vesicle + receptors + A.A vesicle
what happens to the AP when it reaches the pre-synaptic terminal of SC?
- when AP reach the pre-synaptic terminal they trigger the NT release that binds to post-synaptic terminal which has ion channels and receptors
which receptors and channels are present on the post synaptic terminal?
pre-synaptic - voltage gates Ca2+ channels (Ca2.1 channel)
and ligand gates ion channels
What happens if you stop nociceptors from sending their signals into the CNS? Can we achieve this? How?
- Stopping nociceptors means no pain
- Lidocaine is a local anaesthetic used while extracting tooth, dulls the pain only where it is applied
- blocking of Na2+/Ca2+ channels locally to prevent the AP firing
Describe the following terms
1. Hyperalgesia - increased pain to suprathreshold stimulus, decreased pain threshold, spontaneous pain
2. Allodynia - usually non-painful sensory stimulus but now painful
3. Hypoalgesia - reduced perception of pain, decreased responses, increased pain threshold
4. Analgesia - relief or reduction of pain perception
what is the role of inflammatory mediators in nociception?
- when there is an activator (for e.g. heat from capsaicin) the nerve ending release cGRP and substance P which then act on blood vessels resulting leakage of blood vessels
- the leakage results in the release of plasma cells, white cells and leukocytes into the extracellular space
- these leukocytes activate/attract inflammatory mediators through the receptors present on them like histamine, TNF-alpha, NO, IL-1,8 which is released from tissues
- these mediators then act on the receptors on the sensory nerve endings and make them more sensitive or change the number of receptors
- these terminals are more readily activated in the presence of activator stimulus resulting in hyperalgesia
- this also results in release of NA and prostaglandins from the post-synapse
when are noxious stimulators released and what impact do they have?
they are released on injury/disease in periphery tissues and they can cause acute pain and sensitise afferent systems
name TWO receptors the noxious stimulators act upon in acute pain?
1. TRKA (tropomyosin receptor kinase A) - receptor for NGF (nerve growth factor)
how does injury in peripheral tissues cause acute pain?
injury -> NGF -> noxious stimuli -> acts on receptors -> increases SubP, cGRP, Na+, Ca2+ channels at DRG
how do immune cells mediate pain sensitisation?
immune cells release inflammatory mediators which act on their respective receptors which modulate the sodium channels, TRPA,TRPV activity resulting in increased pain sensitisation
which are the immune cells involved in pain sensitisation?
1. mast cells
4. Th17 cells
what is excitability? and its role in pain?
- is the relationship b/w stimulus applied to a neuron and the pattern of AP firing produced
- in other words a stimulus vs response measure for AP
- the sensitised states in pain produce a change in the excitability
the amount of current required to produce 1 AP
what are the FOUR ways to increase excitability?
1. DEPOLARISE THE RESTING POTENTIAL - close resting K+ channels or open Na+/Ca2+/non-selective cation channels
2. INCREASE THE RESTING MEMBRANE RESISTANCE - close channels that are open at resting poential (e.g. leak K+ channels)
3. CHANGE ACTIVITY OF SUB-THRESHOLD VOLTAGE GATED CHANNELS - increase voltage dependent opening of low threshold (T-type) Ca2+ channels or decrease opening level of low threshold K+ channels
4. MAKE AP MORE HYPERPOLARISED - change gating properties of Na+ channels to increase max available Na+ channel conductance
why do researchers study the sensory neuron cell body while investigating AP in pain?
1. because it is very big which makes it easier
2. it is currently impossible to record AP intracellularly at the peripheral terminals of sensory neurons as they are very small because the AP is adjacent the sensory terminal
what is the structure of Na+ channel?
it is 24 transmembrane protein wrapped around not a circle and ions go through the middle It also has voltage sensors and includes pharmacological binding sites
which Na+ channels are found in pain sensing neurons?
9 sodium channels are found in normal pain sensing neurons
- the main ones involved in mediating pain are NaV1.3, NaV1.7, NaV1.8 and NaV1.9
on which gene is NaV1.7, NaV1.8 and NaV1.9 present?
NaV1.7 - SCN9A
NaV1.8 - SCN10A
NaV1.9 - SCN11A
which two mechanism result in hyperalgesic state?
1. peripheral sensitisation - increase responsiveness at peripheral nociceptive terminals
2. central sensitisation - increase responsiveness of dorsal horn neurons
which are the two pathways NGF mediates inflammation post an injury?
1. NGF acts on its receptor TrkA, TRPV1 channel and Nav 1.8 resulting in release and increase in substance P, CGRP, Na+ and Ca2+ channels acting on DRG
2. NGF acts on mast cells to release histamine, bradykinin, serotonin, PGE, which acts on DRG again to increase substance P, CGRP, Na+ and Ca2+ channels