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Visceral pain Sydney Broome Fremantle
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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
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Definitions © Eric J. Visser 2017 UNDA. All rights reserved
© Eric J. Visser 2017 UNDA. All rights reserved
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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
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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
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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 © Eric J. Visser All rights reserved
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-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
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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
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Afferent & efferent nerve pathways Afferents carry CNS inputs
Afferents Arrive Efferents carry CNS outputs Efferents Exit © Eric J. Visser 2017 UNDA. All rights reserved
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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
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afferents run with sympathetic nerves
Visceral afferents run with sympathetic nerves © Eric J. Visser 2017 UNDA. All rights reserved
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Transmission of visceral sensation
Limbic system Visceral spinal cord pathways Dorsal horn Viscera Visceral afferents © Eric J. Visser 2017 UNDA. All rights reserved
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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