IPS Week 3 Summary PDF

3.1 unpacking transmission 5 steps of nociception 1. transduction 2. conduction 3. transmission 4. modulation 5. transmission definition transmission is the process of neural activation and an impulse or action potential that is generated. • this stage begins at the synapse bw 1st (via Lissaue...

3.1 unpacking transmission 5 steps of nociception 1. transduction 2. conduction 3. transmission 4. modulation 5. transmission definition transmission is the process of neural activation and an impulse or action potential that is generated. • this stage begins at the synapse bw 1st (via Lissauer’s tract) and 2nd order neurons at dorsal horn of sc and ends in brain perception follows AP s that ascend 2nd-order afferent pathways like the spinothalamic tract and carries information on pain, temp, and crude touch to terminal synapses in the brain, such as the thalamus. • doesn’t end in thalamus • continues via 3rd and 4th order neurons to other structures in the brain dorsal horn contains a network of interneurons & 2nd order neurons that are architecturally classified by REXED LAMINAE rexed laminae • gray matter laminae that are associated w prim neuron types: A beta, A delta and C fibers • interneurons are nerves that allow for communication bw sensory or motor nerves and the CNS • neurons can also modulate sensory input- either facilitate or inhibit nocicepetion at the PNS or CNS • 2nd order neurons project input into thalamus • interneurons have a role sensory modulation & in descending inhibition rexed laminae • part of post gray column or dh of sc • fxnally: mediate synapses bw 1st order neurons (w interneurons) and 2nd order neurons (structures work as a intermediary processing center for sensory info) 1. lamina 1: 2nd order neurons on interneurons: marginal zone; synapse w A delta and C fibers- mediate info of pain, crude touch and temp 2. lamina 2: aka substantia gelatinosa- synapses w c fibersmediates sensory info on slow noxious stimulu from mechanical, thermal and chemical recpetors (perceived as secondary pain) 3. lamina 3: 4. lamina 4: receives presynaptic terminals from A beta neurons 5. lamina 5: receives presynaptic terminals from A delta 6. laminae 6: has presynaptic terminals from A alpha neurons neurons lamina 1 & 2: heavily involved in mediation of info associated w nociception lamina 3 & 4 form the nucleus proprioception lamina 5 and 6: form base of post gray column 2nd order neuron activation 2nd order neuron synapse on 3rd order neurons, then 3rd onto 4th neurons. these neurons are found in the sc and brain 2nd order neurons associated w nociception are nerves that direct info (noxious stimulus), from 1st order neurons in the DH , along the sc as part of the spinothalamic tract, up thru the brainstem and into the thalamus 2nd-order neurons follow pathways that project info on somatic nociception, both superficial and deep, both immediate and local info to visceral nociception, slow and nonspecific info from the viscera AND mediate emotional and autonomic responses to nocicepetion “SAVE” 3rd and 4th-order neurons then project nociceptive info from presynaptic terminals w 2nd order neurons to other structures w/in brain ex: primary somatosensory cortex this will then predicate the modulation of nociception & experience of pain. pre-synaptic terminal physiology once an AP reaches the pre-synaptic jxn bw 1st order and 2nd order and interneurons, the 1st order neurons release additional substances or neuropeptides that activate the synapses of either interneurons or 2nd-order neurons. primary neuropeptides released by A-delta 1st order neurons is glutamate, while the primary neuropeptide released by first-order C fibers at the synapse jxn is substance P • anatomically occurs in rexed laminae • most involved are rexed laminae 1 & 2 type of neurons that synapse on lamina I are stimulus specific: mechan chem, or temp, and can be mediated by A delta or C fibers. vs neurons that synapse on lamina II considered to be multireceptive or polymodal, and are mediated primarily by C fibers. once a nociceptive AP is generated at 2nd-order neuron, it will be transmitted to the brain via ascending afferent pathways like the spinothalamic tract (ST) From the ST to other structures of the brain via 3rd and 4th order neurons as part of transmission. summary 3.2 Transmission Systems & Pathways Introduction - Anterolateral System - Signals nociception thermal sensation & non-discriminatory touch - Spinothalamic tract is 1 part of this system - Other tracts are the spinoreticular & spinomesencephalic tract - Spinothalamic Tracts - A complex arrangement of ascending 2nd order neurons within anterolateral system - Carries both noxious & non-noxious info from A beta, A delta, C-Fibers from periphery to thalamus - Pathways - Anterior Pathway - Lateral Pathway - Neospinothalamic - Youngest in terms of biological evolution - Paleospinothalamic - In b/w Neo- & Archi- Archispinothalamic tract - Tract is older - Prior to medulla, many 2nd order neurons travel independently of spinal column - All carry information that terminate in thalamus Important Note - Spinoreticular & Spinomesencephalic tracts travel parallel to spinothalamic - Not traditionally considered to be a part of spinothalamic tract Take Aways - Anterolateral system is umbrella architectural categorization of sensory pathways that ascend sc to brain - Spinothalamic tracts made of 3 phylogenetically unique ascending 2nd order neurons - Neo, Paleo, Archispinothalanmic Tracts - Anterolateral system has established pathways through sc to brain 3.4 brain projections medulla and pons projections from the medulla and pons to the reticular formation 1. neospinothalamic (A delta)- few projections in medulla and pons 2. paleospinothalamic (C fibers) 3. archispinothalamic (C fibers) these two more in pons and medulla anatomically rf extends entire length of the brainstem (hind & midbrain) info delivered to the rf originates from C-fibers via branches of the paleo and archi tracts -neo: quicker fibers w heavier myelination -responsible for providing us our immediate experience of pain rf is our primary center for regulation of sensory arousal, and levels of consciousness such as being asleep or being awake direct output of stimulus sent to RF therefore, projections are • responsible for alertness to pain info from RF sent to parafascicular, the central medial thalamus, the hypothalamus, the limbic system, as well as the primary somatosensory cortex ultimately reproduce out autonomic visceral and emotional response • to pain c fibers: carry nociceptive info response for visceral pain • periaqueductal gray PAG and tectum • via spinoreticular tract & tectum via hind and mid brain spinomesencephalic and/or spinotectal tract (interchangeable) projections from mid-brain to PAG and tectum 1. neospinothalamic 2. paleo (c fibers) 3. archi (c fibers) primary contributors of projections to PAG and tectum • tectum is main mediator for how we reactively behave to nociception • PAG: alter sensory input before it’s experienced & mediate sympathies responses to sensation • projections responsible for inhibition, facilitation of input and autonomic responses to nociception • PAG and tectum have diffuse 3rd order synaptic connections include: modularity rf, parafascicular, centromedian thalamus, hypothalamus, limbic system and primary somatosensory cortex - will mediate additional inputs outside of just our autonomic response to nociception - will include emotional and visceral response thalamus and primary somatosensory cortex projections from 1. neo (a delta)- primarily come from for thalamus and PSC 2. paleo (c fibers) 3. archi ( c fibers) • 95% of fibers being delivered to thalamus from ST come from neo and ant pathways • v small contributions of archi and paleo • tracts terminate at VPI and even more at VPL of thalamus VPI= ventral post inf aspect of thalamus VPL= ventral pst lat aspect of thalamus • nociceptive and discriminatory info from the neo tract coming from A-delta and C-fibers are then sent to the sensory cortex via 3rd order neurons and the same can be said for the paleo and archi tract. - info sent to somatosensory cortex via 3rd order neurons summary 3.5 Visceral Nociception Visceral Nociception - slow & non specific pain 1. 2. afferent sensory n from viscera broadly distributed across DRG & spine overlapping/bilateral distribution of afferent n (not segmentally oriented) - unlike acute somatic noxious stim & neurons (segmental) 3. decreased ratio of afferent fibers to cell bodies - less info but more interpretation cross talk b/w visceral & somatic neurons! -ascending info goes through paleo & archispinothalmaic tracts referred pain - MSK urinary tract • hyperpathia • nociplastic pain: central sensitization • chronic manifestation of pain female reproductive organs biliary tract • liver • gallbladder • bile ducts Summary • unlike somatic nociception, visceral nociception = slow & non specific • distribution of visceral pain is patterned & associated w/ generalized overlapping & bilateral distribution of afferent n • referee visceral pain & referred MSK pain = 2 distinct pathophysiological processes 3.6 Transmission Illustrated Anterior Lateral System info on nociception, thermal sensations, non discriminatory touch • 3 pathways • - spinothalamic - spine reticular - spinomesencephalic spinothalamic tract mainly w/ nociception • lateral • anterior • archi • neo (A delta & C but mainly A delta) • paleo (C fibers) • C fibers • noxious stimulus • doesn’t join until medulla Neo Paleo Anterior archi • crude touch • pressure • A delta & C fibers 3.7 Unpacking Modulation Modulation: endogenous inhibiting or facilitating nociception at the dorsal horn & second order neurons via central/peripheral pathways Analgesic modulation • 2 theories - gate control all tell us how body modulates pain - descending analgesic systems control in form of decreasing pain experience Endogenous Facilitation Example central sensitization • Endogenous = originating from an organism/internal/self mediated Nociceptive modulation = reactive process Noxious stimulation = can change how we experience pain • body can modulate nociceptive info, enhancing it/inhibiting it before reaching brain internal processes regulating both ascending and descending inputs and outputs (like endogenous control) Gate Control Theory Melzack and Wall 1965 • non noxious stim can acutely reduce magnitude of nociceptive AP reaching the dorsal horn of SC • before nociceptive info reach brain specialized receptors responsible • more peripheral - meissner - pacinian - ruffini light touch pathways this helps stop the pain before we feel it!! - merkel Descending inhibition systems • activation of mid and hind brain = inhibit/facilitate nociceptive input to brain through descending neural pathways • neurons synapse w/ dorsal horn of SC & directly influence propagation of nociceptive AP at 2nd order neurons!! • mediates persistent nociceptive modulation (chronic pain) • modulates nociceptive input going into body central sensitization • enhanced sensitivity of danger transmissions in CNS • CNS more responsive to facilitating neurotransmitters • involve brain, immune system, endocrine system, cognition behavior central & peripheral sensitization are not the same!!! Summary • gate control theory ACUTELY reduce magnitude of nociceptive AP before nociceptive info reaches brain • descending inhibition systems thought to inhibit chronic nociception & modulated by brain unlike gate control theory • central sensitization facilitates experiences w/ pain through a process of increased Central and Peripheral neuronal responsiveness to neurotransmitters 3.8 Gate Control Theory OBJECTIVES; How DCML pertains to Gate Control Understand physiological process and architectural organization of the Gate control GateControlTheory= NONnoxious stimulus can acutely reduce magnitude of nociceptive action potential arriving at the dorsal horn of the spinal cord before pain signals reach our brain. These receptors that mediate non-noxious stimuli Meissners corp, pacinian corp, ruffini, Merkels Mediated by interneurons carrying sensory info from non-nociceptive alphaBeta fibers at the dcml Afferent neurons that encode TOUCH are not to be confused with Afferent neurons that encode NOXIOUS stimulus. TOUCH = DCML light touch, two pt, conscious propriocept, vibrations (NO head) 2nd order neurons have descending neurons that intersect with inhibitory interneurons In the substantia gelatinosa. These branches of descending neurons Adelta or Cfiber neurons, inhibit either the cell body of the substantia gelatinosa,. This releases GABA which impairs the production of action potential at the second order nociceptive neurons. Will have to relisten to this and rewrite. 3.9 descending inhibition systems theory of descending inhibition 1. activation of specific mid and hindbrain neurons inhibit (or facilitate) nociceptive input to our brain thru descending neuronal pathways *focusing on inhibition for this lecture* 2. descending neurons synapse w inter-neurons at the dh of sc can directly influence propagation of nociceptive APs and 2nd order neurons • 3. mediated persistent nociceptive modulation & scenarios of chronic pain PAG: heavily involved • -nociceptive input mediated process of descending inhibition stimulation 3 prim neural sources responsible for mediating descending inhibition system and nocicepetion at PAG 1. paleo tract 2. limbic nuclei 3. prim somatosensory cortex projection of paleo include: spinomescencephaic fibers limbic nuclei: cingulate gyrus, hypothalamus and insular cortex PVG: periaqueductal gray PAG is extension of PVG • for this course always include PVG when talking about PAG • PAG and PVG release special chemicals to help modulate pain (w some inhibiting neurons, DH) role of endogenous opioids at level of birdbrain is unknown -likely to serve many roles including: inhibiting fear associated with pain and disinhibition of descending pain pathways both the mid and hindbrain produce chemicals, as well as the dh produce chemicals in order to control or modulate our experience of pain periaqueductal gray what does it do? propagates & modulates pain according to the National Library of Medicine, PAG, is a key structure in the propagation of pain modulation, sympathetic responses and learning an action of defensive and aversive behaviors. from the PAG, nociceptive input causes a chain reaction of events to occur in other areas of the brain and sc which leads to special chemicals- inhibit pain at level of dorsal horn brain order of events that lead up to the activation of nociceptive inhibiting interneurons found in dh • all release special chemicals that act on DH local coeruleus releases norepinephrine reticular formation and raphe nucleus magnus release serotonin • all descending neurons travel together by passing thru post lat aspect of white matter until they synapse on nuclei (interneurons on DH) 2nd order neuron 1. inhibitory neurons as part of interneurons at the level of the 2nd lamina of dh 2. norepinephrine and serotonin stimulate the release of enkephalins, endorphins and dynorphins; endogenous opioids. 3. these chemicals inhibit primary and second order neurons. =thereby decreasing production of APs of our nociceptive system (aka decrease our experience of pain) summary 1. one of the functions of the periaqueductal gray matter is that it modulates and propagates pain. 2. numerous systems feed input into the periaqueductal gray, which mediates descending nociceptive inhibition. 3. norepinephrine and serotonin released at the dorsal horn inhibit primary and second order neurons. 3.11 Modulation Illustrated Gate Control Theory - Mediates immediate acute pain - Mediated by peripheral factors acting on dorsal horn - At rexed laminae 2 - Analgesic Effect - Interacts & snaps w/ junction b/w 1st order & 2nd order neurons, associated w/ C- Fibers - States that touch is going to modulate nociceptive input Ascend w/o synapsing, first order neurons travel to medulla & synapse on nuclei & cells around medulla where they cause action potentials w/ 2nd order neurons Synapses on rexed laminae 2 of dorsal horn, at some point A beta neurons interact w/ sensory neurons, giving nociceptive input Zooming in on Rexed Laminae 2 Collaterals that descend down to the rex laminae, synapsing on inhibitory neurons Input will turn on interneurons, will release chemicals (GABA), which will inhibit chemicals released by 1st order synapsing on 2nd order Decreases action potential generation at 2nd order neurons 3.10 CENTRAL SENSITIZATION OBJ Define Central sensitization Differentiate between central and peripheral Know the cuntional nociceptive changes because of central sensitization And Recall theorized primary mechs of central sensitization Lets remember Inflammation is a response to tissue damage, the acute presentation starts healing responses in the body also protects us through chmical mediation of nociception sensitization to nociceptive stimulus PERIPHERAL = normal and enhanced sensitivity of danger transmission in the peripheral nervous system, that causes primary hyperalgesia and heat sensitivity This happens at the level of the DORSAL GANGLIA, FIRST order neurons, and Associated receptors Hyperalgesia= increased sense of pain, increased sensitivity to pain DIFFERENCES b/t central and peripheral CENTRAL = requries higher threshold for activation. Longer stimuli(duration) and repeated stimulus peripheral = sensitization elicited by activation of nociceptors central= does not need activation of nociceptors Peripheral= increase local sensitivity to noxious stimuli and heat Central= increase local sensitivity to mechanical stimulus Central Sensitization= increased responsiveness of nociceptive neurons in the CNS compared to the normal subthreshold of efferent input This means central mechanisms propagate systemwide changes and noxious stimuli sensitivity as well as transmission of nociceptive input Following an injury, central sensitization is secondary hyperalgesia This can lead to pain mitigation in some areas, even increased sensitivity in areas outside of the original area of nociception WOLF MOLIERE pain is generated as a consequence of changes within the CNS rather than just a reflection of the presence of peripheral noxious stimulus MECHANISMS for central sensitization 4 main processes Homosynaptic potentiation Windup nerves= increase in action potential output from dorsal horn neurons and activation of nociceptive neurons in C Fibers. Temporary plasticity Heterosynaptic potentiation Long lasting neuroplasticity. Increases responsiveness for hours in the dorsal horn neurons after the primary noxious stimulus occurs. Allodynia- painful response to nromall nonpainful stimulus, occuring after primary hyperalgesia symptoms Neuron Immune Cell Interations Inhibitory Dorsal Horn Interneurons mediate longer lasting changes in the central nervous system hyperalgesia, secondary hyperalgesia, and allodynia can last for days weeks months and even years. Descending Inhibitory Pathway - More centrallzedmeans to mediate nociception, more chronic conditions - Analgesic Effect - Interacts & snaps w/ junction b/w 1st order & 2nd order neurons, associated w/ C-Fibers - More centrallzed Input received, series of events happens, sends descending neurons to other parts of brain to produce chemicals - Archi Paleo LC - Locus Coeruleus RF.- Reticular Formation RN - Raphe Nuclei PVG & PAG leads to down chain and inhibits action potentials associated with noxious stimulus Input into each part which will activate local nuclei, which will produce chemicals Collaterals join spinal mencephalaic tract & go into PAG (Periaqueductal Gray) Noxious input through DRG, synapse on dorsal horn, cross white commissure, ascend Closer Look Inhibitory cells turned on & generate action potential, synapses on junction b/w 1st & 2nd order neurons The inhibitory cells produce very special chemical, endogenous opioids Inhibits production of action potentials, that’s a lot more effective than GABA Take Aways - Gate Control Theory acutely reduce the magnitude of nociceptive action potentials before informing reaches brain - Descending is thought to inhibit chronic nociception - Process is mediated by the brain, unlike Gate Control Theory clinically • differentiate b/w presentation of each tract • know what each tract does neuroplasticity hetero: more than one thing synapsing homo: one specific thing coming in synapsing to change the state of neurological system know which laminae belong w/ what fibers and from which tract paleo/archi - 2 archi - 4 dorsal horn - true processing of info DRG - unipolar Synchronous Session Two Faculty Name PT, PhD Jeffrey Foucrier PT, DPT Orthopedic Clinical Specialist modulation- AP changed Activity: Pairing – Ordered Neurons 1. First 1. Transduction 2. Second 2. Conduction 3. Third 3. Transmission 4. Fourth 4. Modulation info leading to higher brain & perception :( thermal, chemical, mechanical noxious Activity: True/False – Dorsal Horn interneurons activated around DH then sent to jxn • Neurons in the Dorsal Horn can modulate sensory input? True / False • Interneurons of the Dorsal Horn are nerves are restricted to communication between sensory nerves and the central nervous system only. different tracts True / False • The Dorsal Horn contains both first and second ordered neurons. True / False (& interneurons) Activity: Discussion – Laminae Lamina 1 • • • • • Lamina 2 • • • marginal zone a delta & c fibers first pain, crude touch & temp (nociceptive stand point) mainly mechanical & temp Neospino Primarily • • substantia gelatinosa c fibers noxious stimulus: thermal, mechanical, and chemical Slower pain Archi and Paleo NOT UWU how is your art always on omg point Activity: Table – Primary Nociceptive Pathways Brain Structure(s) Medulla and Pons and their associated synapsing structures. Primary Contributor(s) – Multiple Choice Outcome - Discussion visceral emotional autonomic Paleo / Archi / Neo modulation: inhibition/facilitation PAG and Tectum and there associated synapsing structures. Thalamus and Primary Somatosensory Cortex visceral, emotional and autonomic Paleo / Archi / Neo acute/first pain Paleo / Archi / Neo crude touch temp Activity: Role-Play – Descending Inhibition gate control - something interrupts the pathway to make it not as painful? Yes, thats essentially gate control but there was a end section that was a bit confusing descending inhibition - Descending inhibition is Alexis’s drawing. Go Alexis! Teach Dr Stern lol i didnt see this til now How might you explain this process to Dr. Stern? Discussion: Descending Inhibition vs. Gate Control sorry y’all i was so confused lol he lost me here… - nadia Activity: Discussion – Visceral Nociception Why is visceral nociception experienced as a diffuse and non-descript sensation of pain? 1. <Enter Text> Breaking it down… • <Enter Text> Activity: Group Discussion – Pain Science in Practice 1. What is the take-away from our required Week 2 reading? 2. Why is the information we have been covering this far into the course important from a clinical perspective?