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60 Cards in this Set
- Front
- Back
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Nociception |
the neural coding/processing of noxious stimuli (from the Latin "nocer" - to injure/hurt) |
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Noxious Stimuli |
(involved with nociception)
stimuli that can elicit tissue damage and activate nociceptors |
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Nociceptors |
- sensory receptors that detect signals from damaged tissue (or the threat of damage) and also respond to chemicals released from the damaged tissue - free (bare) nerve endings found in the skin, muscle, joints, bone and visera |
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The Pain Pathway |
- anterolateral system - pain processing is independent of normal cutaneous processing |
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Nociceptors Only Active When |
- stimuli reach higher intensities than other receptors can encode (plateau in firing) - direct stimulation of large fibers (Ia, II, Aβ) doest not produce pain |
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Peripheral Axons and Painful Stimuli |
peripheral axons responsible for normal stimulation do not increase their frequency in response to painful stimuli |
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(3) Types of Nociceptors (Fibers) |
- Aδ Type I - Aδ Type 2 - C Fibers |
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Peripheral Nociceptive Axons.. |
terminate in "free nerve endings" |
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C Fibers |
- polymodal - respond to thermal, mechanical, and chemical stimuli - respond equally to all types of noxious stimuli -unmyelinated: result in 2nd (dull) pain |
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Aδ Fibers |
- respond to intense mechanical and thermal stimuli - myelinated: result in 1st (sharp) pain - Type I and Type II |
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Type I Aδ Fibers |
- respond to dangerous mechanical and chemical stimulation - do not respond well to heat |
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Type II Aδ Fibers |
- respond to thermal stimulation (heat) - do not respond well to mechanical and chemical stimulation |
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(4) Functional Categories of Skin Nociceptors |
1. high threshold mechano-nociceptors 2. thermal nociceptors 3. chemical nociceptors 4. polymodal nociceptors |
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High Threshold Mechano-Nociceptors |
(skin nociceptor)
- respond only to intense mechanical stimulation such as pinching, cutting, or stretching |
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Thermal Nociceptors |
(skin nociceptor)
- respond to intense mechanical stimulation as well as to thermal stimuli |
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Chemical Nociceptors |
(skin nociceptor)
- respond only to chemical substances |
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Polymodal Nociceptors |
(skin nociceptor)
- respond to all high intensity stimuli (like the other skin nociceptors) |
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Joint Nociceptors |
the joint capsules and ligaments contain:
- high-threshold mechanoreceptors - polymodal nociceptors - "silent nociceptors" |
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"Silent" Nociceptors |
only respond to the onset of inflammmation |
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Visceral Nociceptors |
visceral organs contain:
- mechanical pressure nociceptors - temperature nociceptors - chemical nociceptors - "silent" nociceptors |
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Heat-Sensitive TRP Channels |
- Aδ and C fiber nerve endings contain Transcient Receptor Potential (TRP) channels - respond to temperature, pressure, and inflammatory agents - TRPV1, TRPV2, TRPA1, and ASIC |
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TRPV1 |
- "Transient Receptor Potential Vanilloid Type-1" channels (also known as "capsaicin receptor" or "vanilloid receptor 1") - likely developed to detect endovanilloids (which resemble capsaicin and/or endocannabinoids - a nonselective cation channel permeable for Na(+) and Ca(2+) |
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TRPV1 is Activated By: |
- heat (>43ᴼ C) - Anandemide (an endocannabinoid) - Capsaicin (the pungent compound in hot chili peppers) - allyl isothiocyanate (the pungent compound in mustard and wasabi) |
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Threshold at Which Heat is Perceived as Noxious |
>43ᴼC |
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Endovanilloids are Produced: |
peripherally in response to injury |
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TRPV2, TRPA1, and ASIC |
("ASIC" is "Acid-Sensing Ion Channels")
- act as mechanoreceptors or for the detection of chemical irritants |
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Hyperalgesia |
- increased sensitivity to painful stimuli (eg. increased temperature sensitivity after sunburn) - peripheral effect at the level of the nociceptors - most sensitizing pro-inflammatory agents activate the phospholipase C pathway |
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How Pain Becomes Sensitized: |
tissue damage and inflammation causes release of inflammatory mediators (such as prostaglandins, histamine, and Substance P) which increase the sensitivity of nociceptors to noxious stimuli |
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Most Sensitizing Pro-Inflammatory Agents Activate the: |
Phospholipase C Pathway
- Protein kinase C phosphorylates TRPV1 leading to sensitization of TRPV1 |
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Allodynia |
- pain sensation in response to non-painful stimuli - increase in the excitability of dorsal horn neurons (innocuous stimuli like touching the skin) activates 2nd order neurons in dorsal horn that receive nocieptive inputs |
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"Wind Up" - Allodynia |
persistent increases in excitability and synaptic transmission |
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Anterolateral System |
ascending pathways that convey: - pain - temperature - crude touch - (includes other functions as well) |
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(3) Types of Pathways in Anterolateral System |
- Spinothalamic tract - Spinoreticular tract - Spinotectal tract
(equally important for pain perception) |
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Spinothalamic Tract |
(anterolateral system)
- destination: thalamus - function: localization of painful or thermal stimuli |
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Spinoreticular Tract |
(anterolateral system)
- destination: reticular formation - function: causes alertness and arousal in response to painful stimuli |
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Spinotectal Tract |
(anterolateral system)
- destination: tectum - function: orients the eyes and head towards the stimuli |
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Dorsal Root Ganglia |
- pathway in Lissauer's tract - C-fibers terminate in 1 and 2 - Aδ fibers terminate in 1 and 5 - 2nd order neurons in Rexed's laminae 1,2, and 5 of spinal cord (layers 1+5 projection neurons to brainstem and thalamus, layer 2 interneurons) - projections from 2nd order neurons cross midline and give rise to anterolateral tract |
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Referred Pain |
- visceral pain misperceived as somatic pain - result of crossing over of signals (in multimodal lamina 5 neurons)
eg. angina: poor perfusion of heart muscle perceived as pain in shoulder, chest, or arm |
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Multimodal Lamina 5 Neurons |
non-nociceptive fibers also terminate in layer 5 so the multimodal lamina 5 neurons integrate both inputs |
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Dorsal Column-Medial Lemniscus vs. Anterolateral System |
- dorsal column-medial lemniscus system (touch) - anterolateral system (pain) - location in spinal cord where pathways cross the midline is different - clinical relevance: unilateral spinal cord lesions lead to "dissociated sensory loss" |
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Unilateral Spinal Cord Lesions |
leads to "dissociated sensory loss" |
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Contralateral Spinal Cord Lesions |
leads to reduction in pain and temperature sensation |
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Ipsilateral Spinal Cord Lesions |
leads to reduction in touch, pressure, vibration, and proprioception |
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Sensory Discriminative Pain Pathways |
- location, intensity, quality - Body: spinothalamic tract - Face: trigemino-thalamic tract |
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How Nociception is Segregated From Normal Touch Perception |
nociception is segregated from normal touch perception up to the level of cortical circuits, because the anterolateral system and the dorsal column system contract different relay neurons in the ventral posterior thalamus |
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Parallel Pain Pathways in the Anterolateral System |
1. sensory discriminative aspects of pain (location, intensity, quality) 2. affective motivational aspects (unpleasant feeling, fear, anxiety) |
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The Interpretation of Pain |
- context specificity (eg. loss of limb on battlefield; athletes during important games) - placebo effect |
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Placebo Effect |
physiological response following administration of a pharmacologically inert "drug" |
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Endogenous Analgesia System |
- descending modulation of pain perception (basis of Placebo effect) - stimulation of the periaqueductal gray in the midbrain is analgesic |
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Periqueductal Gray |
- controls nociceptive neurons in dorsal spinal horn through 4 nuclei in the brainstem - stimulation is analgesic: releases Enkephalins, endorphins, and dynorphins |
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(4) Nuclei in Brainstem |
- Parabrachial nucleus - Medullar reticular formation - locus coeruleus - Raphe Nuclei |
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Gate Theory of Pain |
(Melzack and Wall, 1965) - local interactions in the spinal cord modulate pain perception: - the flow of nociceptive info (thin Aδ and C fibers) through the spinal cord is modulated (reduce) by simulataneous activity in the large myelinated "touch" fibers - eg. rubbing skin after stubbing your toe |
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Opiods |
- peptides that bind to the same postsynaptic receptors as opium - 3 groups of endogenous opioid receptor ligands |
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Active Ingredient in Opium Poppies |
Sap or seeds: morphine |
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Potent Analgesics |
- morphine - heroin - synthetic opiates such as methadone and fentanyl |
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(3) Groups of Endogenous Opioid Receptor Ligands |
- endorphins (endogenous morphine) - enkephalins - dynorphins
(released in the periaqueductal gray) |
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Enkephalins Release |
released directly in the spinal cord to blunt the effects of nociceptor activation |
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Phantom Limbs and Phantom Pain |
- the result of mismatch between internal representation of body and (missing) peripheral input? - likely due to central sensitization at the level of dorsal horn neurons (increase in excitability) |
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Treatment of Phantom Limbs and Phantom Pain |
problematic to treat because of widespread pain processing and cortical reorganization after amputation |
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Prevalence of Phantom Limbs and Phantom Pain |
82% in upper limb amputees 54% in lower limb amputees |
