Pain Flashcards
What is nociception?
Physiological processing of tissue damaging information
Sensory aspect of pain (Somatosensory Component)
How is pain biologically advantageous?
Protective mechanism to prevent tissue injury and permit recovery from injury
What is the international association for the study of pain definition
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (it feels like —-)
Define hyperalgesia
Heightened pain (eg when damaged tissue is exposed to noxious stimulus)
What is allodynia?
Pain arising from gentle touch (painful response to a stimulus that would not normally be painful)
Key feature in chronic pain syndromes
Specific pain pathways allow the _____, _____ and _____ of pain
Specific pain pathways allow the localization, intensity and quality of pain
What is the affective component of pain?
- Production of negative emotion
- Arousal
- Initiation of stress responses
- Interruption of ongoing procedures (pain demands attention)
- Learning - plasticity in painful response
- Stress, anxiety, anticipation make pain worse (second response worse)
What is musculoskeletal and other ‘mild’ pain?
- initial response to tissue damage sensed by _________
- Transmitted by _________ ‘pricking’ pain (first pain)
- Secondary response; ongoing pain caused by release of _________ _________, _________ and _________ at site of lesion (second pain)
- Transmitted by _________ - burning, more diffuse pain - slow pain
- initial response to tissue damage sensed by ‘free nerve endings’
- Transmitted by sensory Adelta-fibres - ‘pricking’ pain (first pain)
- Secondary response; ongoing pain caused by release of bradykinin, histamine, acid metabolites and prostaglandins at site of lesion (second pain)
- Transmitted by C-fibres - burning, more diffuse pain - slow pain
What is Deep pain (Nociceptive pain)?
- Treated with ______
- deep aching pain, felt as deep to the body surface, poorly ______
- Initiated by ______
- Treated with opioids
- deep aching pain, felt as deep to the body surface, poorly localized
- Initiated by major trauma (post-operative pain, injury or childbirth)
- both deep pain and mild pain have been referred to as “good pain” - prevent overuse of damaged tissue and allow healing to occur
both deep pain and mild pain have been referred to as “good pain”, why?
prevent overuse of damaged tissue and allow healing to occur
What is neuropathic pain?
- Chronic pain resulting from ___\____
- Respond poorly to ___\____
- Treat with ___\____, ___\____ or ___\____ such as ___\____ or ___\____
- Chronic pain resulting from nerve injury or infections
- phantom limb pain
- trigeminal neuralgia
- diabetic neuropathy
- post herpetic neuralgia (shingles)
- HIV-AIDS neuropathy
- Respond poorly to opioids
- Treat with antidepressants, cannabinoids or anticonvulsants such as pregabalin or gabapentin
What are the most standard frontline treatments for neuropathic pain?
Pregabalin or gabapentin
Structurally similar to GABA
*Effect Ca++ channels
Why is chronic, neuropathic pain considered bad pain?
No obvious biological function
- injury should have already been recovered so the continued pain response is unecessary
Neuropathic pain:
- ______ onset
- most striking feature:
- Characterized by ______, _______, _______ and _______
Neuropathic pain:
- slow onset - outlasts original injury
- most striking feature: Stimulus independent pain
- Critical because there isn’t a noxious stimuli
- Characterized by allodynia, hyperalgesia, causalgia, and spontaneous (stimulus independent) pain
Pain Pathways:
- Afferent (sensory) neurons reside in ______ along spinal cord - send axons out to innervate body surface
- A-alpha, A-beta fibres:
- _______ ______ conducting
- Carry _______ information
- Convey_____. _____. _____
- Piezo 2 channels are _______
Pain Pathways:
- Afferent (sensory) neurons reside in dorsal root ganglia along spinal cord - axons innervate body surface
- Aalpha and Abeta fibres: non-pain fibres
- Myelinated rapidly conducting
- Large cell bodies and thick axons - heavily myelinated
- Carry innocuous information (non-pain)
- Convey touch, pressure, muscle afferent information
- Piezo 2 channels are mechanosensors
Which A fibres carry painful stimuli?
A-delta
A-delta fibres are:
- Thinly ____ (carry first pain) - slower than A-alpha / A-beta
- ____ conduction velocity (
- High threshold ________
- Terminate primarily in ________ (marginal zone), ________and ________
A-delta fibres are:
- Thinly myelinated (carry first pain)
- Slow conduction velocity (<40m/sec)
- High threshold mechanoreceptors (mechanical nociceptors)
- Terminate primarily in spinal lamina I (marginal zone - superficial region of spinal cord), Lamina II and Lamina V (still upper half (dorsal) spinal cord)
The prototypical pain fibres are the ____ fibres
C-fibres
C-fibres:
- _____ conduction velocity (0.2-1m/sec) because they are:
- ___________
- Terminate primarily in ________
- Specific Classes:
- _______
- __________
C-fibres:
- Very slow conduction velocity (0.2-1m/sec)
- unmyelinated
- Terminate primarily in spinal laminae I and II (marginal zone and substantia gelatinosa)
- Specific Classes:
- Peptidergic
- Non-peptidergic (aka Isolectin B4 Positive (IB4+))
What are the 2 classes of C-fibres and how are they distinct?
- Specific Classes:
-
Peptidergic - express sensory neuropeptides (substance P/CGRP)
- High-threshold mechanoreceptors (strong mechanical stimulation)
- Polymodal nociceptors (noxious heat mechanical stimuli, chemical irritants)
- Mechanical cold nociceptors (skin cooling)
-
Non-peptidergic (aka Isolectin B4 Positive (IB4+)) - no substance P or CGRP
- Low threshold mechanoreceptors (gentle mechanical stimulation)
-
Peptidergic - express sensory neuropeptides (substance P/CGRP)
Images of Abeta and Adelta
Peptidergic C
Non-peptidergic C
All sensory fibres release the excitatory amino acid neurotransmitter to transmit their signals:
Glutamate
A-delta’s and Peptidergic C fibres express, as well as glutamate, ________
A-delta’s and Peptidergic C fibres express, as well as glutamate, sensory neuropeptides (Substance P, CGRP)
Which afferent fibres only express glutamate?
A-alpha and Non-peptidergic C
Pain fibre channels to know:
- Nav1.7/1.8/1.9 (sodium channels)
- Important for AP generation
- These ones are exclusively on pain fibres
- TRPV1
- ion channel that alerts us to things that are hot
- Heat sensor (capsaicin is endogenous ligand for TRPV1)
- In C-fibres:
- Current of TRPV1 in non-peptidergic C is very low
- sensation of heat/burning likely not carried by Non-P C unless there’s previous trauma (hyperalgesia)
- Current of TRPV1 in non-peptidergic C is very low
- IB4 - only on non-peptidergic C (IB4+)
Which Afferent fibres express Nav1.7/1.8/1.9?
- A-delta
- Peptidergic C
- Non-peptidergic C
ie the pain afferents
Which sensory afferents contain TRPV1?
- conveys heat information (capsaicin endogenous ligand)
- On
- Peptidergic C
- A-delta
- Non-peptidergic C (less current through here though, unless previous trauma)
Spinal processing of pain:
- In dorsal horn, pain fibers project to:
- _______ (_______)
- _______ (_______)
- _______
- Contact:
- _______ projection neurons which project to _______, _______, _______ and _______
- Local circuit interneurons involved in _______ and _______ reflexes
- Dendrites of wide dynamic range neurons (_______ and _______)
Spinal processing of pain:
- In dorsal horn (posterior), pain fibers project to:
- Lamina II (substantia gelatinosa)
- Lamina I (marginal zone) - direct connection (A-delta are so fast)
- Lamina V - where some mixing of sensations (allodynia)
- Contact:
- Lamina I projection neurons (second order neuron) which project to brainstem, parabrachial nucleus, hypothalamus and thalamus
- Local circuit interneurons involved in local withdrawal and autonomic reflexes
- Dendrites of wide dynamic range neurons (Lamina IV and V)
Peptidergic C fibres project to _______, majority go to ________
Peptidergic C fibres project to lamina I, majority go to Outer lamina II (substantia gelatonosa)
A-beta myelinated fibres project into _______ and ______
A-beta myelinated fibres project into lamina V and lamina III-IV
- allodynia may be a result of the proximity of Lamina III-IV to lamina I (specifically Inner lamina I) - mixing of signals
Glutamate acts on ________ receptors
Glutamate acts on excitatory NMDA and AMPA receptors
AMPA is faster (A-delta (lamina I))
Substance P and CGRP released by some pain fibres generate __________
Substance P and CGRP released by some pain fibres generate slow excitation of dorsal horn cells —- intensify pain response
co-released with glutamate - summation
Transmission of neurotransmitters in Dorsal horn is modulated by ________
Transmission of neurotransmitters in Dorsal horn is modulated by GABA/glycine interneurons
Inhibitory interneurons - dampen excitatory input
- Some inhibitory interneurons also release _____ and ______ (endogenous opioids)
- Descending pathways from ________ release endogenous opioids
- Descending NA/5-HT inputs from areas in brainstem: ________, ________ and ________
- Modulate ________ of pain
- 5-HT ________
- NA predominantly________
- Some inhibitory interneurons also release encephalin and endorphin (endogenous opioids)
- Descending pathways from Rostroventral medulla (RVM) release endogenous opioids
- Descending NA/5-HT inputs from rostroventral medulla, locus coereleus (LC) and Raphe nuclei
- Modulate spinal processing of pain
- 5-HT mixed excitatory/inhibitory
- NA predominantly inhibitory
Axons to the brain:
Multiple pathways:
- most axons of lamina I and lamina V projection neurons cross midline and ascend in anterolateral quadrant of spinal cord
- 5 tracts:
- Spinothalamic Tract
- Spinoreticular tract
- Spinomesencephalic tract (spinoparabrachial tract)
- Cervicothalamic tract
- Spinohypothalamic tract
Axons to the brain:
Multiple pathways:
- most axons of lamina I and lamina V projection neurons cross midline and ascend in anterolateral quadrant of spinal cord
- 5 tracts:
-
Spinothalamic Tract
- Pain tract
- Spinal cord to thalamus
- Pain tract
-
Spinoreticular tract
- spinal cord to reticular formation
- Critical for alerting capacity of pain (stepped on thumbtac and knew immediately)
-
Spinomesencephalic tract (spinoparabrachial tract)
- layers onto Spinoreticular tract
- Cervicothalamic tract
- Spinohypothalamic tract
-
Spinothalamic Tract
Spinothalamic Tract (medial division): - old
- project to __________
- Thalamus = gateway to the __________
- __________ and __________ aspects of pain
- Association with __________pain
- Lacks __________ organization - input comes from __________ have large __________ fields
- Project widely to __________ and __________ cortex
Spinothalamic Tract (Medial):
- project to intralaminar thalamic neurons
- Thalamus = gateway to the cortex
- Affective and alerting aspects of pain
- Association with slow (second) pain
- Lacks somatotopic organization - input comes from dorsal horn cells have large receptive fields
- Project widely to association and prefrontal cortex
Spinothalamic Tract (Lateral division) - newer
- Projects to __________ (__) nucleus of the thalamus
- __________ organized, __________ and __________ aspects of pain
- Only __________ of VPL neurons are nociceptive
- Project to __________ and __________ lobe
- Associated __________, __________ pain
Spinothalamic Tract (Lateral division) - newer
- Projects to ventroposteriolateral (VPL) nucleus of the thalamus
- Somatotopically organized, localization and discriminative aspects of pain - finer aspects of pain
- Only 10% of VPL neurons are nociceptive
- Project to somatic sensory cortex and parietal lobe
- Associated fast, first pain (A-delta to Lamina I)
