Anatomy and Physiology of Pain Flashcards
Name the 4 steps that are involved in the physiological mechanisms of pain
- Transduction
- Transmission
- Perception
- Modulation
describe the 4 steps that are involved in the physiological mechanisms of pain
- TRANSDUCTION
- Noxious (potentially harmful) stimuli translated into electrical activity at sensory nerve endings - TRANSMISSION
- Propagation of impulses along pain pathways - PERCEPTION
- Descrimination/ affect / motivation - MODULATION
- Stages 1-3 are modified (positive and negative modulation occurs) - this is the idea that you can down regulate pain as we don’t want to be in pain all the time
describe the definition of pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
pain is a ….
…pain is a perception usually but not always associated with tissue-damaging stimuli (nociceptive information)
what does acute pain result form
- this results from the activity of a nociceptor
What is a nociceptor
- a sensory neuron transducing potentially harmful stimuli
Name the two nociceptors
- A delta fibres (myelinated) = these transmit fast pain
- C fibres (unmyelinated) = these transmit slow pain
What do nociceptors cause to happen
- they give signal transduction and transmit across pain pathway
- these leads to withdrawal behaviour via reflexes or perception behaviour which includes pain, avoidance, and emotional reaction
what gene defects can cause a life without pain
Loss of Tranduction/Transmission
Loss of NaV1.7
= (sodium channel subunit)
= Congenital indifference to pain
Loss of C fibres
= trkA - NGF receptor mutation
= Congenital insensitivity to pain with anhydrosis CIPA
What does life without pain result in
- results in shortened life span
- death is often due to secondary consequences of injury such as infections
describe A delta fibres
- Sharp pricking fast pain – thermal and mechanical
- precise localisation of insult/stimulus
- reflex withdrawal
Describe C fibres
Slow burning pain, affect, misery; autonomic effects
what are the two types of C fibres
- ‘peptidergic’ C fibres release peptides peripherally e.g., Substance P / CGRP
= this leas to Vasoactive, promote inflammatory responses (neurogenic inflammation) and healing; thermal nociception - ‘Peptide-poor’ C fibres have distinct receptors (e.g., P2X3 ATP receptors) and projections
= these leads to mechanical nocicpetion
what lamina does central termination of A delta and C fibres occur
C fibres = lamina I and II (they also innervate lamina V through these interneurons)
A delta fibres = Lamina I and lamina V and more deeply into the dorsal horn
where do the axons of nociceptive receptors decussate
- they ducat close to where the nociceptors enter the spinal cord and form the spinothalamic tract
describe the pathway of the anterior spinothalamic (or neospinothalamic) tract
- Primary afferent: Aδ fibres as well as input from C (indirect via interneurons) and Aβ fibres innervate →
- Projection neurones in Lamina V – ‘wide dynamic range cells’. After decussating axons travel in the anterior spinothalamic tract
- innervate ventral posterior lateral (VPL) and ventral posterior medial (VPM) – somatosensory thalamus; and ventral posterior inferior (VPI) and central lateral (CL) nuclei of the thalamus (reticular and limbic associated areas).
- The main projection is to the primary somatosensory cortex (SI) from
VPL/ VPM →; localisation & physical intensity of noxious stimulus
- input to SII (secondary somatosensory cortex) via VPI
- and ACC (anterior cingulate cortex; emotion) and prefrontal cortex and striatum via CL (sites for cognitive function/ strategy)
what fibres mainly enter the anterior spinothalamic (or neospinothalamic) tract
mainly from A delta fibres
describe the pathway of the lateral spinothalamic (or paleospinothalamic) tract
- Primary afferent: C fibres but also some Aδ fibres innervate →
- Projection neurones in Lamina I –After decussating axons travel in the lateral spinothalamic tract
- innervate the more posterior/ medial parts of the thalamus
Mediodorsal nucleus (ventrocaudal) (MDvc)
‘Posterior thalamus’ – posterior nucleus (medial subnucleus) (POm) and ventral medial nucleus (posterior) (VMpo)
(also some projections to the VPL, VPM and CL) - Projections to Cortex MDvc → anterior cingulate cortex (ACC); (emotion/ motivation) Posterior thalamus (POm and VMpo) → anterior or rostral insula (emotion, quality i.e. ‘pain’, autonomic integration)
what system lateral or anterior spinothalamic tract is earlier
Lateral or paleo spinothamaic tract
what does the lateral Lateral or paleo spinothamaic tract receive its main input from
C fibres
what is the difference between the cortical targets of the anterior and lateral spinothalamic tract
Anterior or ‘neo’spinothalamic tract to primary and secondary somatosensory cortex
Lateral or ‘paleo’spinothalamic tract’: anterior cingulate and rostral insular cortex
the axons of the lateral spinothalamic tract also synapse in ….
Axons of the lateral spinothalamic tract synapse in several sites in the brainstem- as well as the thalamus (mainly the posterior, medial nuclei
name three other areas that the lateral spinothalamic tract projects to
- the limbic system
- midbrain reticular formation
- intralaminar(reticular) nuclei of thalamus
describe the three other areas that the lateral spinothalamic tract project to
the limbic system
- subjective sensations of pain
- goes via the brainstem and posterior medial thalamus
Midbrain reticular formation
- pain - induced arousal and descending control of nociceptor input
Intralaminar(reticular) nuclei of thalamus
- alerting cerebral cortex and focus of attention of pain
what is the unpleasant painful character of pain mediated by
- projects of the lateral spinothalamic tract going towards the limbic system
describe the other collateral projections of the lateral spinothalamic projections
Spinal circuitry– Reflexes, integration of information
Reticular formation (and reticular thalamus)- arousal and alerting cortex
Periaqueductal grey (PAG) in midbrain: descending pain modulation
Parabrachial nucleus in pons- from there onward to the amygdala
what do these areas do in terms of pain
- anterior cingulate cortex
- pre-frontal cortex
- insula
- amygdala
- primary sensory cortex
- anterior cingulate cortex = emotional reaction and motivation
- pre-frontal cortex = evaluation and cognition
- insula = pain map, interception, homeostatic adjustment and emotion
- amygdala = aversion, emotional memory and response
- primary sensory cortex = somatosensory, discrimination- location, intensity
describe actue pain
is of sudden onset, usually the result of a clearly defined cause such as an injury. It resolves with the healing of its underlying cause.
describe fast pain
sharp pain conveyed by Aδ elicits reflexive withdrawal to prevent further injury
describe slow pain
burning, lingering, emotionally charged
what are the 4 signs of inflammation
Calor (heat)
Rubor (redness)
Dolor (pain)
Tumor (swelling)
what is peripheral sensitisation
= this is when the area that was damaged becomes sensitised
= this results in hyperalgesia, allodynia, spontaneous pain
= this enables protection and facilitates healing without further damage
- this resolves with healing of the underlying cause
How does peripheral sensation resolve itself
- this resolves with healing of the underlying cause of the pain
What is peripheral sensation caused by
Due to effects of inflammatory mediators (from inflammatory cells and damaged tissue) nociceptors show
= reduction in activation threshold
= increase in responsiveness
what plays a key role in inflammatory pain
= prostaglandins
What targets prostaglandins
NSAIDS
describe how prostaglandins are made
- Phospholipase A2 releases arachidonic acid from cell membranes (driven by inflammatory mediators)- targeted by steroids
- Cyclooxygenase 1 (COX-1) and COX-2 enzymes use arachidonic acid as a substrate for prostaglandin (PG) synthesis
when and where are COX 1 and COX 2 present
- COX-1 normally present in tissue at low levels
- COX-2 induced during inflammation
How do prostaglandins lead to inflammatory pain
PGs sensitise C-fibres by increasing numbers of other receptors and increasing the number of open sodium channels. There are also central (i.e. spinal cord) sensitising effects
What produces central sensitisation
Prolonged nociceptor input onto dorsal horn neuron projection neurons produces
What are the two types of modulation
central sensitisation
peripheral sensitisation
describe how central sensitisation works
- there is prolonged nociceptor input
- the activity dependent increase in excitability of dorsal horn projections outlast the stimulus which caused it in the first place
- this leads to modified responsiveness, the projection neurones show enhanced responses and low leave inputs produce a response and pain, therefore the threshold has been lowered
- this leads to pain such as allodynia, 2nd degree hyperalgesia and spontaneous pain
What is allodynia
Allodynia refers to central pain sensitization (increased response of neurons) following normally non-painful, often repetitive, stimulation.
What is hyperalgeisa
yperalgesia is a condition where a person develops an increased sensitivity to pain.
what do nociceptor afferents release
glutmate and peptides
what can chronic pain arise form
nociceptive pain
describe the definition of chronic pain
Defined as pain of more than 12 weeks by British Pain Society, normally associated with an underlying condition
name the two types of maladaptive chronic pain
Neuropathic pain (due to injury in PNS or CNS) Dysfunctional pain (no known lesion or inflammation
what is maladaptive chronic pain characterised by
Characterised by hyperalgesia, allodynia, spontaneous pain i.e., central sensitisation effects
What are the causes of chronic maladaptive pain
injury, stroke, infection i.e. post-herpetic neuralgia, drug treatments, diabetes, chronic alcoholism, hereditary conditions
where does pain modulation occur
= In the cortex
= From the brain/ brainstem
= In the spinal cord (central sensitisation)
= In the periphery (inflammation)
What theory is at the spinal level that is a modulation theory
gate control theory
describe gate control theory
If you hit your hand painful than if you rub it adds another stimulus and this reduces the painful stimulus going up to the CNS
- this has a role of TENS, lamina II interneurones
describe what the midbrain periaqueductal gray does
- this is a descending system that modulates the transmission of ascending pain signals
- it is inhibitory or facilitating
- this effects the parabrachial nucleus, medullary reticular formation, locus coeruleus, and raphe nuclei
describe how acupuncture works
- activates A delta fibres
- this stimulates the periaquaductal grey through diffuse noxious inhibitory control (DNIC) of pain
- this pain can inhibit pain
what are key mediators of endogenous analgesic mechanisms
lamina II interneurons are key mediators of endogenous analgesic mechanisms.
what causes the intensity of the pain
- superior parietal lobe and insula and amygdala pathway
What feeling causes the unpleasantness of pain
ACC - PFC - PAG path emotion/ placebo control– unpleasantness
= Sensitive to μ opioid antagonist - naloxone
