7 - Anatomy and Physiology of Pain Flashcards
4 Physiological mechanisms of pain
Transduction
Transmission
Perception
Modulation
TRPV1 receptor
Heat & Acid
ASIC
Acid
TRPM8
Cold/menthol
What is transduction
When noxious stimuli is converted into electrical activity at sensory nerve endings
Transmission
Propagation of impulses along pain pathways
Perception
Discrimination/affect/motivatoin
Modulation
Where 1-3 are modified
Pain
Unpleasant sensory and emotional experience
Nociceptor pain
Normal pain caused by tissue damage
activity of a nociceptor
receptor proteins on membranes of nociceptor allow response to tissue damaging stimuli
Loss of transduction/transmission malfunction
Loss of NaV1.7
Congenital indifference to pain
Loss of C fibres
TrkA - NGF receptor mutation
congenital insensitivity to pain
with anhydrosis CIPA
What are Adelta nociceptors
Sharp pricking fast pain
Precise location of insult/stimulus
Reflex withdrawal
What are C fibres
Slow burning pain affect
Peptidergic C fibres
Release substance P/CGRP - Vasoactive
Promotes inflammatory response
Peptide poor C fibres
Have distinct receptors - P2X3 ATP
mechanical nociception
What lamina do C fibres innervate
I and interneurons II
also V via interneurons
What lamina do Adelta fibres innervate
Laminae I and V
Where do projection neurons decussate
Close to where the nociceptors enter the spinal cord
Projection neurons
Second order neurons
Carry pain message onwards from the primary afferent
Function of the neospinothalamic tract
To protect you e.g move your arm when faced with pain
What is the input to the ASST
Ad and C fibres (indirect)
What lamina do the projection neurones travel in the ASST
lamina V
What parts of the thalamus does the ASST inntervate
VPL - Ventral Posterior Lateral
VPM - Ventral Posterior Medial
VPI - Ventral posterior Inferior
CL - Central lateral
Which parts of the thalamus project to primary somatosensory cortex
VPL
VPM
Which parts of the thalamus project to the secondary somatosensory cortex
VPI
ACC
CL
What is the function of the paleospinothalamic tract
Slow feeling of pain
Punishing aspect
What are the primary afferents of the LSST and what lamina do the projection neurons travel in
C fibres
some Ad fibres
Lamina I
What part of the thalamus does the LSST innervate
MDvc - Mediodorsal ventro caudal
POm - Posterior nucleus - medial subnucleus
VMpo - Ventral medial nucleus posterior
What does MDvc project to
Anterior Cingulate Cortex
What does the posterior thalamus (POm and VMpo) project to
Anterior or rostal insula
What does the limbic system mediate
Subjective sensations of pain and pleasure
What does the midbrain reticular formation mediate
Pain - induced arousal and descending control of nociceptor output
What does the Intralaminar nuclei of the thalamus mediate
Alterting the cerebral cortex and focus of attention on pain
Collateral projections of the LSST and their function
Spinal Circuitry - Reflexes Reticular formation(arousal and alerting cortex) Periaqueductal Grey (PAG) - Midbrain, descending pain modulation Parabrachial nucleus - inpons, on to amygdala
ACC
Emotional reaction/motivation
PFC
Evaluation
cognition
Insula
Pain map, emotion
Amygdala
Emotional memory and response
Primary Somatosensory Cortex
Somatosensory discrimination
Location
Intensity
Reason for peripheral sensitation
Enables protection and facilitated healing
4 cardinal signs of infalmmation
Calor - heat
Rubor - redness
Dolor - pain
Tumor - swelling
What happens in peripheral sensitisation
Due to effects of inflammatory mediators
Reduce in activation threshold
Increase in responsiveness
How does peripheral sensitisation occur
Na channels - NaV1.8 and 1.9 change thresholds for opening and kinetics
TRPV1 channels increase sensitivity to heat
How are prostaglandins formed
Phospholipase A2 releases arachidonic acid (driven by inflammatory mediators)
COX-1 and COX-2 enzymes use arachidonic acid as a substrate for PG synthesis
Which COX is present in tissues all the time?
COX-1
How do PGs sensitise C fibres
Increase the number of other receptors and increase the no of sodium channels
What causes central sensitisation
Prolonged nociceptor input onto dorsal horn neuron projection neurons
Chronic Pain
Pain of more than 12 weeks
Can become maladaptive
What is neuropathic pain
pain due to abnormality in the PNS or CNS
what are the characteristics of malladaptive pain
Hyperalgesia
Allodynia
Spontaneous pain
How would you treat maladaptive pain
Anticonvulsants
Anti-depressants
What/where are the inhibitory interneurons
At lamina II
Modulate the transmission of ascending pain signals
Counter stimulation Analgesi
Stimulation of Ab fibres that stimulation inhibitory lamina II
reduced C fibre transmission
Uses convergence which is the idea that 2 different sensory inputs fuse into 1 when travelling up the spinal cord)
How does acupuncture work
Via activation of Ad fibres
stimulates via PAG mediated Diffuse Noxious Inhibitory Control of pain
Pain can inhibit pain
TENS
Transcutaneous electrical nerve simulators
Used to stimulate Ab fibres - discriminative touch
Stimulate inhibitory lamina II interneurons
What does the PAG stimulate
Locus coerulus
Nucleus raphe magnus
Reticular Formation
Locus Coeruleus
Transmits NA
Nucleus raphe magnus
Transmits serotonin and encephalin
Reticular formation
Sympathetic arousal
NA release
Activation of inhibitory lamina II
