What it Takes to be a Pain Pain Pathways and the Neurophysiology of pain Dennis S. Pacl, MD, FACP, FAChPM Austin Palliative Care/ Hospice Austin A Definition of Pain complex constellation of unpleasant sensory, emotional and cognitive experiences provoked by real or perceived tissue damage and manifested by certain autonomic, psychological, and behavioral reactions Bonica s Management of Pain. 3rd ed. Philadelphia, Pennsylvania, USA: Lippincott Williams and Wilkins; 2003:73. CNS - Spinal Cord Spinal Layers Spinal grey matter is divided into 10 layers Substantia Gelatinosa Composed of a layer of cell bodies running up and down the dorsal horns of the spinal cord Receive input from A and C-fibers Activity in SG inhibits pain transmission http://upload.wikimedia.org/wikipedia/commons/thumb/c/c0/medulla_spinalis_-_substantia_grisea_- _English.svg/2000px-Medulla_spinalis_-_Substantia_grisea_-_English.svg.png 1
https://stahlonline.cambridge.org/essential_4th_chapter.jsf?page=chapter10_summary.htm&name=chapter%2010&title=summary http://thebrain.mcgill.ca/flash/d/d_03/d_03_cl/d_03_cl_dou/d_03_cl_dou.html Action Potentials https://bealbio.wikispaces.com/on+line+a nd+upload+period3+nervous+system 2
Nociceptor Types Skin Nociceptors - Skin nociceptors may be divided into four categories based on function. High threshold mechanonociceptors Thermal nociceptors Chemical nociceptors, which respond only to chemical substances (Figure 6.2). Polymodal nociceptors Silent Nociceptors Allan I. Basbaum; Thomas M. Jessell; The Perception of Pain - http://www.ib.cnea.gov.ar/~redneu/2013/books/principles%20of%20neural%20science%20- %20Kandel/gateway.ut.ovid.com/gw2/ovidweb.cgisidnjhkoalgmeho00dbookimagebookdb_7c_2fc~30.htm 3
Sensory Nerve Receptors Receptor Actions May initiate ion flow after binding their ligand (ionotropic) May convert extracellular stimuli to intracellular responses by G-protein driven second messenger systems (metabotropic) or by Trk mechanisms that induce a succession of protein phosphorylations. Many ligands have both ionotropic and metabotropic receptors Ion Channels Four main types of voltage-gated ion channels and transporters Sodium, potassium, chloride, and calcium channels allow ions to flow down their electrochemical gradients when they are open Transporters actively pump ions against their gradient. The Na, K, and Cl channels induce changes in membrane potential when they are activated electrically, mechanically, or chemically. The altered membrane voltage then affects other voltagesensitive (voltage-gated) molecules. http://www.rnceus.com/ages/nociceptive.htm 4
Factors Modulating Nociceptors Neurotrophs 5
Theories of Pain Specificity Theory (Descartes 17 th C) Pain is hardwired: Specific modality, like vision or hearing, with its own central and peripheral apparatus and projects to a pain center Pattern Theory (Frey and Goldscheider, 1894) Pain is produced by intense stimulation of nonspecific receptors since there are no specific fibers and no specific endings Stimulus intensity and central summation are the critical determinants of pain In the trenches Dr Henry Beecher (1959) Severely wounded soldiers on the beach at Anzio during World War II, only one out of five soldiers required morphine When Dr. Beecher returned to his practice after the war, he noticed that trauma patients with similar wounds were more likely to require morphine (one out of three) Dr. Beecher concluded that there was no direct relationship between the severity of the wound and the intensity of pain. The meaning attached to the injuries in the two groups explained the different levels of pain. Unifying the Theories Physiologic evidence on spinal mechanisms, together with the evidence demonstrating central control over afferent input, led to a new theory of pain mechanisms that is consistent with the concepts of physiologic specialization (specificity) AND those of central summation and input control (pattern) 6
Gate-Control Theory (1960 s) Ronald Melzack and Patrick Wall A Gate Control System modulates sensory input from the skin before it evokes pain perception and response Described physiological mechanism by which psychological factors can affect the experience of pain Neural gate can open and close thereby modulating pain Gate Control Involves 3 Systems Skin stimulation evokes nerve impulses that are transmitted to three spinal cord systems Cells of the Substantia Gelatinosa The Dorsal Column fibers projecting toward the brain, which act as the trigger for central control Central Transmission Cells (projection neurons) in the Dorsal Horn Opening and Closing the Gate When the gate is open pain signals excite dorsal horn transmission cells When the gate is closed signals from small diameter pain fibres do not excite the dorsal horn transmission neurons. 7
Three Factors Involved in Opening and Closing the Gate The amount of activity in the pain fibers. The amount of activity in other peripheral fibers. Messages that descend from the brain. Conditions that Open the Gate Physical conditions Extent of injury Inappropriate activity level Emotional conditions Anxiety or worry Tension Depression Mental Conditions Focusing on pain Boredom 8
Conditions That Close the Gate Physical conditions Medications Counter stimulation (e.g., TENS, heat, massage) Emotional conditions Positive emotions Relaxation, Rest Mental conditions Intense concentration or distraction Involvement and interest in life activities Gated Pain Theory 9
Pain control schema 10
Medical Treatments for Pain Skin Stimulation Massage Great as an adjunct TENS Mixed results Acupuncture Effective for a number of types of pain Reduces the need for meds Psychosocial Interventions to Improve Coping w/pain Hypnosis Biofeedback Relaxation Training Behavior Modification Cognitive Therapy/CBT Multimodal Approaches The Centre for Integrative Medicine University of Toronto 11
This is Your Brain on Placebo Brain regions with greater release of endogenous opioids during placebo administration in subjects with high levels of resilience, straightforwardness and altruism and low levels of angry hostility. Photo Credit: Marta Pecina/University of Michigan Is it important for you to know that opioids work beyond the mu receptor? Opioid Receptor Proinflammatory Cytokines Opioids Activate Glia Neuron Glia 1,2 Glial glutamate transporter NMDA receptor activity Dopamine release Dorsal horn-> nociceptive firing-> PAIN VTA-NAc-> dopamine -> REWARD Analgesia Proinflammatory Neuroplasticity Cytokines Pain & Reward Increased reward Hyperalgesia (M3G) References Perception of Pain http://www.ib.cnea.gov.ar/~redneu/2013/books/prin ciples%20of%20neural%20science%20- %20Kandel/gateway.ut.ovid.com/gw2/ovidweb.cgisidnj hkoalgmeho00dbookimagebookdb_7c_2fc~30.htm Pain and the Neuromatrix (Wall) http://www.jdentaled.org/content/65/12/1378.full.pdf Activated Glia and Pain http://www.anzca.edu.au/fpm/events/fpmevents/activated-glia-as-culprits-in-opposing-opioidanalgesia-driving-tolerance.html 12