1. Visceral pain
Sydney
Broome
Fremantle

2. Viscera (L. viscus): internal organs of the body
Definitions
Viscera (L. viscus): internal organs of the body
“Affecting inward feelings”, from Middle French viscéral and directly from Medieval Latin visceralis "internal," from Latin viscera, plural of viscus "internal organ, inner parts of the body," of unknown origin. The bowels were regarded as the seat of emotion in medieval times (see gut feelings to follow!).
Soma (Gk. somatikos): pertaining to the body
© Eric J. Visser 2017 UNDA. All rights reserved

3. Definitions © Eric J. Visser 2017 UNDA. All rights reserved
© Eric J. Visser 2017 UNDA. All rights reserved

4. Visceral pain Definition
‘Pain arising from the internal organs of the body’ (IASP 2012)
Smooth muscle ‘tubes’
-gastrointestinal
-genitourinary
-vasculature (heart)
Covering membranes (peritoneum, pleura, pericardium)
Parenchyma-solid organs (liver, pancreas, thyroid)
-not much ‘sensation’ from solid organs
Can present as acute, chronic, cancer, nociceptive, neuropathic pain
© Eric J. Visser 2017 UNDA. All rights reserved

5. Visceral pain Key issues Major health care problem & disease burden
Under-recognised compared with musculoskeletal pain
GIT diseases (appendicitis, IBS, inflammatory bowel disease, GORD)
Dysmenorrhoea
Labour pain
Pelvic pain syndromes
Renal colic
Ischaemic chest pain
© Eric J. Visser 2017 UNDA. All rights reserved

6. Functions of visceral sensation
Organ homeostasis, feedback & control
Monitoring internal bodily environment
-’interoception’
Conscious monitoring (hunger, satiety, voiding)
Sub-conscious monitoring (bladder, bowel)
Reflex organ functions (peristalsis, menstruation)
External environmental monitoring
-gut lumen is a major ‘interface’ with environment
Gut-brain axis & microbiome
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7. -Suggests visceral nociception is not that important
nociceptors
Only 15% of the body’s nociceptors are found in visceral organs
-Suggests visceral nociception is not that important
-Suggests pain is NOT the primary function of visceral nociceptors
-Organisms can’t do much about tissue damage in internal organs anyway, so why
bother evolving a ‘high-tech’ pain alarm?
-Pain is only triggered if there is severe tissue damage to an organ
Visceral nociceptors are polymodal receptors
-They respond to a variety of stimuli, not just tissue damage
-High threshold (take quite a bit of stimulus to fire)
Mainly thin, non-myelinated C-fibres
-Slow-conducting, slowly-responsive (onset-offset), dull, vague pain
© Eric J. Visser 2017 UNDA. All rights reserved

8. Visceral nociceptors -full bladder, bowel
Mechanoreceptors (‘stretch & strain’)
-full bladder, bowel
Chemoreceptors
-Protects body from ingested toxins e.g. plants
(triggers pain, nausea)
-TRPV1 ion channels (H+, capsaicin, chilli)
-TRPM8 ion channels (menthol)
-Triggers
-Chemical (plant alkaloids e.g. opioids)
-Inflammation (inflammatory bowel disease)
-Neuro-immune
-Ischemia (myocardial infarction)
© Eric J. Visser 2017 UNDA. All rights reserved

9. Afferent & efferent nerve pathways Afferents carry CNS inputs
Afferents Arrive
Efferents carry CNS outputs
Efferents Exit
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10. Visceral sensory afferents
Visceral afferents (mainly C-fibres) run along-side sympathetic efferent nerves
They hitch-a-ride with sympathetic nerves going to visceral organs
Reflects embryology: organs need autonomic & sensory innervation, so both types of nerves run together
Don’t get confused: nociception (pain) is NOT transmitted by the sympathetic nerves themselves, but by the visceral afferents running with them
© Eric J. Visser 2017 UNDA. All rights reserved

11. afferents run with sympathetic nerves
Visceral
afferents run with sympathetic nerves
© Eric J. Visser 2017 UNDA. All rights reserved

12. Transmission of visceral sensation
Limbic system
Visceral
spinal cord pathways
Dorsal horn
Viscera
Visceral afferents
© Eric J. Visser 2017 UNDA. All rights reserved

13. Visceral spinal cord pathways
Mainly spinal-parabrachial-limbic pathway & dorsal columns
Located in the midline of the spinal cord
Transmits nociception, pressure, stretch, chemical ‘information’
‘Primitive’, slow-conducting & slowly-responsive system
Midline spinal cord pathways were the first to develop in evolution
-Still the major sensory & nociceptive pathway in lower vertebrates & crustaceans
The lateral spinothalamic pathway evolved later, transmitting ‘fast’ easy-to-localise sensory information from the body’s outer surface
© Eric J. Visser 2017 UNDA. All rights reserved

14. Spinal cord sensory pathways
© Future Neurol 2007
Thalamo-cortical system
Limbic system
Primitive emotional brain
Amygdala (fear)
Hypothalamus (autonomic)
Hippocampus (memory)
Spino-parabrachial-limbic pathway
Earliest evolutionary pathway
primitive
Monitors internal environment
Visceral pain
Midline spinal cord
Ends in mid brain (limbic)
Slow
Vegetative
Emotional
Spinothalamic pathway
Later evolutionary pathway
Monitors external environment
Somatic pain > visceral pain
Lateral spinal cord
Ends in thalamus & cortex
Fast
Reactive
Sensory
Visceral afferent nociceptive
C-fibre
© Eric J. Visser 2017 UNDA. All rights reserved

15. By comparison: lateral spinothalamic pathway
Lateral spinothalamic pathway (LST) transmits nociception, temperature
The major spinal cord nociceptive pathway
Transmits nociception from external environmental interface (skin, somatic tissues), also some visceral nociception
LST developed later in evolution when organisms interacted more with their environment—needed a rapid-response to external threats
The already existing midline spinal cord sensory pathways were too slow & non-specific for the task
The LST is part of the rapid-response, easy-to-localise somatic tissue damage alarm system
© Eric J. Visser 2017 UNDA. All rights reserved

16. Visceral pathways end in the limbic brain
Pain ‘relay station’
Autonomic
Cingulate gyrus
Visceral spinal pathways end in limbic system
‘Primitive’ midbrain
‘Arche-cortex’
’Lizard brain’
Limbic system explains strong emotional, behavioural, autonomic, motor & memory responses seen in visceral pain
Fear & anxiety
Panic
Angor animi
Memory of pain
Visceral nociception &
sensory information
© Eric J. Visser 2017 UNDA. All rights reserved

17. Most chest pain presentations have a ‘panic’ component
Example of links between visceral pain, limbic activation & panic Cardiac angst
Most chest pain presentations have a ‘panic’ component
Acute coronary syndrome activates the limbic system (amygdala) causing anxiety & ‘panic’. Conversely…
A panic attack can trigger chest pain in the absence of coronary disease (very common in the ED)
Many patients having a heart attack feel a sense of ‘impending doom’ (angor animi) which is a panic attack variant
Linked to limbic system activation (anxiety, autonomic responses)
Need to treat visceral anxiety as well as pain
© Eric J. Visser 2017 UNDA. All rights reserved

18. Somatosensory
cortex
Visceral organs are poorly represented in the somatosensory cortex
That’s why it’s difficult to localise visceral pain in our body
Lack of cortical representation of visceral organs helps explain referred pain
Sensory homunculus (body-map)
© Eric J. Visser 2017 UNDA. All rights reserved

19. Referred
pain
Definition: Pain that is experienced in a different part of the body to the site of nociception
Sensory afferents from viscera & somatic tissues share a common connection in spinal dorsal horn
Dorsal horn convergence
Because visceral organs are not well represented in the SSC body-map, when the dorsal horn is activated by visceral afferents, the SSC misinterprets these signals as coming from somatic afferents
© Eric J. Visser 2017 UNDA. All rights reserved

20. Dorsal horn convergence
Nociceptive afferents from heart converge at same level of spinal dorsal horn as somatic afferents from T2/3 (dermatomes)
T2/3
dorsal horn level
T2/3
dermatome
Because the heart is poorly represented in the SSC body-map, the cortex ‘thinks’ nociceptive signals from the T2/3 dorsal horn are coming from somatic tissues & skin at that level
The brain therefore generates referred pain in the T2/3 body-map area
© Eric J. Visser 2017 UNDA. All rights reserved

21. Visceral referred pain
‘viscerotomes’
Pain : Pain that is experienced in a different
part of the body to the site of nociception
appendix
Originally from Cousins and Bridenbaugh's Neural Blockade in Clinical Anesthesia and Pain Medicine
© Eric J. Visser 2017 UNDA. All rights reserved

22. Definition: Nociception in a visceral organ
Referred
visceral-somatic
pain sensitization
(allodynia)
Definition: Nociception in a visceral organ
increases pain sensitization (allodynia)
in somatic tissues (muscle & skin) which share
the same dorsal horn level (convergence)
Anti-dromal nerve activation
Neurogenic inflammation in tissues
Muscle tenderness, trigger points
Cutaneous allodynia
Sympathetic & vascular changes
Tissue oedema
Chest wall muscle & tissue sensitivity in angina
© Eric J. Visser 2017 UNDA. All rights reserved

23. visceral-visceral sensitization (allodynia)
Referred
visceral-visceral sensitization (allodynia)
Definition: Nociception in a visceral organ
increases pain sensitization (allodynia)
in nearby organs which share the same
dorsal horn level (convergence)
Nociception from the bowel produces a reflex increase in
pain sensitization (allodynia) & reflex muscle activity in the bladder
via shared dorsal horn innervation
© Eric J. Visser 2017 UNDA. All rights reserved

24. pain sensitization (allodynia)
Examples of referred
pain sensitization (allodynia)
Visceral-somatic allodynia
-loin muscle tenderness & trigger points in renal colic
-chest wall tenderness & swelling in angina
-epigastric muscle tenderness in peptic ulcer pain
Visceral-visceral allodynia
-peptic ulcer pain & biliary colic
-irritable bowel & irritable bladder
-irritable bowel & dysmenorrhoea
-reflux oesophagitis & angina
Originally from Cousins and Bridenbaugh's Neural Blockade in Clinical Anesthesia and Pain Medicine
© Eric J. Visser 2017 UNDA. All rights reserved

25. Spreading pain sensitization
A key message
Chronic pain in one organ can lead to increased pain sensitivity
in other nearby organs or somatic tissues
Spreading or referred allodynia
Reason why its so difficult to manage chronic abdominal pain
-e.g. A women with irritable bowel syndrome develops dysmenorrhoea
-e.g. A man with reflux oesophagitis has worsening angina pectoris
-e.g. A woman with Crohn’s ileitis pain develops chronic pelvic pain
© Eric J. Visser 2017 UNDA. All rights reserved

26. Gut feelings “Gut feeling” ‘’Trust your gut’’ “I’m sick with stress”
“Butterflies”
“Aching heart”
In medieval Europe, emotions
were thought to be produced
by the intestines & later by
the heart
© Eric J. Visser 2017 UNDA. All rights reserved

27. Gut feelings Interoception: monitoring our internal bodily environment
Gut (like the skin) is a major interface with the external environment
Food, toxins, pathogens, immune system
Is this basis of our ‘gut feelings’?
Gut feelings warn us that ‘something is wrong’
Angor animi is a gut feeling that ‘I’m going to die’
-a sense of impending doom often experienced in acute coronary syndrome
© Eric J. Visser 2017 UNDA. All rights reserved

28. Gut-brain axis & microbiome Gut
Neuro-immune
Brain
Neuro-endocrine
Gut is sometimes called the ‘second brain’
Complex neural web found in gut
Gut & brain share same neurotransmitters
Gut’s microbiome produces 95% of body’s serotonin
Influences brain function (mood)?
“Crohn’s personality”?
© Eric J. Visser 2017 UNDA. All rights reserved

29. Comparing visceral & somatic pain Visceral pain Somatic pain
(key information)
Visceral pain
Somatic pain
Few nociceptors (15%)
C-fibres
Many nociceptors (75%)
A-δ fibres
Function: homeostasis > nociception
Function: nociception > homeostasis
Transmission with autonomic nerves
Transmission in somatic nerves
Terminates in superficial dorsal horn (I,II,V)
Terminates in deeper dorsal horn (II,V,X)
Medial (slow) spinal cord pathways
Spino-parabrachial-limbic, dorsal columns
Lateral (fast) spinal cord pathway
Spinothalamic
Terminates in limbic brain
‘Primitive’ mid-brain Limbic-hypothalamic-autonomic system
Termination in thalamus & cortex
Neocortex
Pain: slow onset & offset
burning, aching, gripping, colicky
Pain: fast onset & offset
sharp, throbbing
Pain ≠ tissue damage
Pain ≈ tissue damage
© Eric J. Visser 2017 UNDA. All rights reserved

30. Comparing visceral & somatic pain Visceral pain Somatic pain
(key information)
Visceral pain
Somatic pain
Pain is poorly localised (midline, torso)
Localised with flat of hand
Pain is well localised (‘lateralized’)
Localised with tip of finger
Referred pain
Minimal referred pain
↑ Emotion & pain behaviour (distress)
(Limbic system)
↓ Emotion & pain behaviour
Pain more likely to be remembered
Pain less likely to be remembered
↑ Autonomic response
Sympathetic & parasympathetic
↓ Autonomic response
‘Vegetative’ motor response
‘Rest & recover’ (rest & digest)
‘Reactive’ motor response
Flight, run away from danger
Evolutionary primitive pain system
Evolutionary advanced pain system
Monitors internal environment
Monitors external environment
© Eric J. Visser 2017 UNDA. All rights reserved

31. Visceral pain Summary of key messages
Pain from internal visceral organs
Visceral nociception monitors internal bodily environment (interoception)
Mainly C-fibre nociceptors (polymodal, high threshold)
Transmitted via ‘slow’ midline spinal cord pathways
Projects to limbic system (midbrain)
Poor cortical representation of visceral sensation (somatosensory cortex)
Poorly-localized pain (midline, diffuse, deep, dull, aching, ‘colicky’)
Referred pain is common
High levels of emotional & behavioral distress (grimacing, groaning, rolling-around) (limbic activn)
-anxiety & panic are very common (‘angor animi’ in heart attack)
Autonomic responses (nausea, sweating, vasovagal, diarrhea) (limbic activn)
Vegetative motor responses (rest & digest)
Primitive pain system in evolutionary terms (compared with somatic sensory system)
© Eric J. Visser 2017 UNDA. All rights reserved

32. Visceral pain Key learning outcomes Definition of visceral pain.
IMPORTANT: List the main differences between visceral & somatic pain (see table).
Visceral nociceptive afferents are mainly C-fibres.
Visceral afferents travel with sympathetic nerves in the periphery.
Visceral & somatic afferents converge in the spinal dorsal horn.
Visceral sensation is transmitted via ‘slow’ midline spinal cord pathways that terminate in the limbic system (midbrain).
Limbic system controls emotional & autonomic responses which are very common in visceral pain.
Understand that anxiety, panic & distress are very common in visceral pain & linked to limbic system activation.
Understand the classical concept of angor animi with cardiac chest pain.
© Eric J. Visser 2017 UNDA. All rights reserved

33. Visceral pain Key learning outcomes
Referred pain: Pain that is experienced in a different part of the body to the site of nociception.
Understand mechanism & features of referred pain & the concept of dorsal horn convergence.
Understand that pain (nociception) in one organ can increase pain sensitization in
nearby organs or somatic tissues due to dorsal horn convergence.
This is called referred visceral pain sensitization (allodynia) & is a common cause of
difficult-to-manage chronic abdominal pain.
Understand common visceral pain syndromes: ischaemic chest pain, appendicitis, renal colic, dysmenorrhoea, irritable bowel syndrome, labour pain, pancreatic cancer pain.
Understand the concepts of the gut-brain axis & gut microbiome.
© Eric J. Visser 2017 UNDA. All rights reserved