Pain physiology Flashcards
(25 cards)
What are the 4 types of nociceptors?
Thermal
- activated by heat or cold
- A delta fibres
Mechanical
- activated by high pressure
- A delta fibres
Polymodal
- activated by mechanical, thermal and/or chemical (pH, bradykinin and histamines)
- C fibres
Silent:
- normally inactive but can become activated in response to noxious stimuli released by tissue injury
What are the 2 types of neurons that convey nociceptive signals, and what type of pain do they generate?
A delta
- fast pain
- temperature (heat)
C
- slow pain
- temperature (cold)
What are the 3 substances that can activate peripheral nociceptors?
Potassium (from damaged cells)
Serotonin (from platelets)
Bradykinin (from plasma)
Histamine (from mast cells)
What are the 3 substances that can sensitize peripheral nociceptors?
Prostaglandins (from damaged cells)
Leukotrienes (from damaged cells)
Substance P (neuropeptide from damaged nerves)
What are the 7 chemicals that create an inflammatory soup and activate and sensitize peripheral nociceptors?
Activate:
- potassium
- serotonin
- bradykinins
- histamine
Sensitize:
- prostaglandins
- leukotrienes
- substance P
What are the 4 effects of inflammatory chemical soup on peripheral nociceptors?
- lower threshold for AP generation
- potential for ectopic AP generation
- increased receptive field size
- recruitment of silent nociceptors
What are the 4 steps in the nociceptive pathway?
- transduction (generation of an AP in a primary afferent nociceptor / PAN)
- transmission (transmission of nociceptive signal from 1st order to 2nd order neuron in the dorsal horn of the spinal cord; from the 2nd order neuron to the 3rd order neuron in the VPN of the thalamus; and termination of the 3rd order neuron in the primary somatosensory cortex)
- modulation (occurs in dorsal horn; includes descending inhibitory pathways, presence of excitatory or inhibitory subtances, and interaction between incoming signals ie: gate control theory)
- perception (thalamus and sensory cortex - sensory discriminative; reticular formation and limbic system - motivational affective; hypothalamus - ANS response)
What are the 3 types of neurons involved in transmission and modulation in the dorsal horn?
Interneurons:
- can be excitatory or inhibitory
Wide Dynamic Neurons:
- receive input from both noxious and non-noxious neurons via interneurons
Projection cells:
- project to brain
What are the 4 types of neurons transmitting signals to the dorsal horn of the spinal cord, and what type of information do they convey?
Noxious:
- A delta (fast pain, heat)
- C (slow pain, viscera, cold)
Non-noxious:
- A alpha (somatic mm, propioception)
- A beta (touch, vibration, pressure)
Describe the 5 steps in the spinothalamic pathway
- 1st order neuron (PAN) transmits AP from periphery to dorsal horn of spinal cord
- modulation of signal in dorsal horn (via interneurons, gate theory, descending inhibitory pathways, presence of excitatory or inhibitory substances)
- synapse between 1st and 2nd order neurons in dorsal horn via interneurons and/or wide dynamic neurons
- 2nd order neuron decussates at spinal cord and ascends to VPN in thalamus; synapses with 3rd order neuron
- 3rd order neuron terminates in primary somatosensory cortex
What are transient receptor potential channels?
TRP channels:
- respond to a number of strong stimuli
- also involved in transmission of burning sensation of chilli
- capasin can be used as an analgesic by targeting TRP channels
Which neurons in the dorsal horn of the spinal cord may be responsible for referred pain?
Wide dynamic neurons:
- receive input from both noxious and non-noxious pathways via interneurons
- may be responsible for referred pain via misinterpretation of incoming stimuli
What are the 2 primary pathways that transmit noxious signals?
Spinothalamic (from body)
Trigeminal (from face)
What are the 2 neuropeptides?
Substance P
CGRP (calcitonin gene-related peptide)
- released by PANs, can play a role in peripheral sensitization
What are the 3 major areas of the brain that play a role in pain perception, and which elements of the pain experience do they contribute to?
- Thalamus and somatosensory cortex - sensory discriminative aspect
- Anterior insular, cingulate cortices, reticular system and limbic system - motivational affective aspect
- Hypothalamus - ANS response
In the dorsal horn, which 2 receptors facilitate the transmission of nociceptive signals; and which 2 receptors inhibit the transmission of nociceptive signals?
Facilitate:
- substance P
- glutamate (NMDA and non-NMDA - AMPA and GABA)
Inhibit:
- serotonin
- norepinephrine
In the dorsal horn, which 2 receptors facilitate the transmission of nociceptive signals; and which substances can be used to inhibit these receptors and therefore inhibit the transmission of nociceptive signals?
Facilitate:
- substance P
- glutamate (NMDA and non-NMDA - AMPA and GABA)
Substances inhibiting these receptors:
- ketamine (NMDA receptors)
- baclofen (GABA receptors)
Other inhibitory substances:
- calcitonin
- octreotide (somatostatin receptors)
- clonidine (alpha 2 receptors)
What are NMDA receptors?
- receptors in dorsal horn
- normally inactive
- become activated by a barrage of APs releasing chemicals into the dorsal horn
- facilitate transmission of nociceptive signals at dorsal horn
- involved in neuropathic pain and central (secondary) hyperalgesia
- inhibited by ketamine
Which substances are released by the descending inhibitory pathway, and what are their actions?
Seratonin and norepinephrine
- directly released by neuron descending from PAG via RVM
Endogenous opioids:
- release from interneurons in the dorsal horn (release triggered by serotonin and norepinephrine from the descending inhibitory neuron)
Actions:
- inhibits release of substance P and AP from 1st order neuron
- hyperpolarizes 2nd order neuron and makes generation of a nociceptive AP less likely
Describe the descending inhibitory pathway
- originates in PAG
- neuron travels to RVM and lateral pontine tegmentum and synapses with 2nd neuron
- 2nd neuron descends to dorsal horn of spinal cord; releases norepinephrine and serotonin and causes the release of endogenous opioids from interneurons in the dorsal horn
Actions:
- inhibits release of substance P and transmission of AP from 1st order neuron (PAN)
- hyperpolarizes 2nd order neuron to make generation of an AP less likely
Briefly describe the 4 steps involved in the generation of an action potential.
- membrane of neuron resting at 70mv
- sodium or calcium enters membrane via voltage gated channels, depolarizing membrane
- action potential generated at 40mv
- membrane of neuron repolarizes by closing calcium or sodium channels, and opening potassium channels
Briefly describe the 6 steps involved in synaptic transmission of an action potential
- AP arrives at the pre-synaptic axon terminal
- AP opens calcium gated channels on axon terminal membrane
- calcium triggers release of neurotransmitter from pre-synaptic neuron into synaptic cleft
- neurotransmitter travels across synaptic cleft and binds to receptors on post-synaptic neuron
- neurotransmitter triggers opening of sodium or calcium channels on post-synaptic neuron
- post-synaptic neuron depolarizes, AP generated at 40mv
What is the difference between the PAG, the RVM, and the VPL?
PAG:
- periacqueductal gray
- area of the brain that initiates descending inhibitory pathways
RVM:
- rostral ventral medulla
- synapse between 1st and 2nd neurons in descending inhibitory pathway
VPL:
- ventral posterolateral nucleus in thalamus
- site of synapse between 2nd and 3rd order neurons in ascending spinothalamic tract
Describe the points of synapse between neurons in the spinothalamic tract
- 1st and 2nd order neurons synapse in the dorsal horn of the spinal cord
- 2nd and 3rd order neurons synapse in the VPL (ventral posterolateral nucleus) in the thalamus
- 3rd order neuron terminates in the primary somatosensory cortex of the parietal lobe
