Pain, July 2001.ppt


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Pain, July 2001.ppt

  1. 1. PAIN <ul><li>The task of medicine is to preserve and restore health and to relieve suffering. </li></ul><ul><li>Pain is an unpleasent sensation </li></ul><ul><li>Pain is universally understood as a signal of disease. </li></ul><ul><li>It is the most common symptom that brings a patient to a physician's attention. </li></ul>
  2. 2. PAIN <ul><li>Pain is divided into acute & chronic </li></ul><ul><li>Acute pain last less than one month, after the injury that produces it is healed </li></ul><ul><li>Chronic pain last more than one month, after the injury that produce the pain is healed. </li></ul>
  3. 3. PAIN <ul><li>Pain represents a “massive worldwide” socio-economic impact </li></ul><ul><ul><li>Pain is the main reason for medical consultation </li></ul></ul><ul><ul><li>Chronic pain treatment implies in US: </li></ul></ul><ul><ul><ul><li>More than 2 million are incapacitated p/y </li></ul></ul></ul><ul><ul><ul><li>More than 100 million work days are lost p/y </li></ul></ul></ul><ul><ul><ul><li>The cost of medical, surgical, rehabilitation, especial devices is more than 70 billion dollars p/y. </li></ul></ul></ul><ul><ul><ul><li>Treatment of pain is one of the most remunerative business to drugs companies. </li></ul></ul></ul>
  4. 4. PAIN <ul><li>The function of the pain sensory system is to: </li></ul><ul><ul><li>Detect </li></ul></ul><ul><ul><li>Localize </li></ul></ul><ul><ul><li>Identify tissue-damaging processes. </li></ul></ul><ul><li>Important diagnostic clues used to evaluate the response to treatment are: </li></ul><ul><ul><li>Quality </li></ul></ul><ul><ul><li>Time course </li></ul></ul><ul><ul><li>Location of a patient's pain complaint </li></ul></ul><ul><ul><li>Location of tenderness </li></ul></ul>
  5. 5. PAIN <ul><li>THE PAIN SENSORY SYSTEM </li></ul><ul><li>Pain is often described in terms of: </li></ul><ul><ul><li>Physical stabbing, burning, twisting, tearing, squeezing </li></ul></ul><ul><li>Emotional reaction </li></ul><ul><ul><li>Terrifying, nauseating, sickening. </li></ul></ul><ul><ul><li>Pain has a duality characteristic </li></ul></ul><ul><ul><li>It is both a “sensation” and “emotion” </li></ul></ul><ul><ul><li>Acute pain is associated with behavioral arousal and a stress response with increased: </li></ul></ul><ul><ul><ul><li>Blood Pressure </li></ul></ul></ul><ul><ul><ul><li>Heart rate </li></ul></ul></ul><ul><ul><ul><li>Pupil diameter </li></ul></ul></ul><ul><ul><ul><li>Plasma cortisol levels </li></ul></ul></ul>
  6. 6. PAIN <ul><li>THE PAIN SENSORY SYSTEM </li></ul><ul><li>DEFINITIONS </li></ul><ul><li>Noxious stimuli is an internal or external stimuli that could elicit the activation of “pain receptors” , this could be: </li></ul><ul><ul><li>Chemical </li></ul></ul><ul><ul><li>Mechanical </li></ul></ul><ul><ul><li>Thermal </li></ul></ul><ul><ul><li>Polymodal </li></ul></ul><ul><li>Nociception is the perception of signals evoked by activation of nociceptors at the C.N.S. To provide information of tissue damage </li></ul>
  7. 7. PAIN <ul><li>THE PAIN SENSORY SYSTEM </li></ul><ul><li>DEFINITIONS </li></ul><ul><li>Fast pain: </li></ul><ul><li>Is a short well localized sensation that is well matched to the noxious stimuli. </li></ul><ul><li>Starts & stops abruptly when stimuli is applied or removed. </li></ul><ul><li>Is strictly associated to the skin (Prick, sharp pain) </li></ul><ul><li>Transsmitted by A-Delta fibers </li></ul>
  8. 8. PAIN <ul><li>THE PAIN SENSORY SYSTEM </li></ul><ul><li>DEFINITIONS </li></ul><ul><li>Slow pain: </li></ul><ul><li>Is a throbbing, burning or aching sensation, is poorly localized & less especifically related to the stimuli. </li></ul><ul><li>The onset has a long latency following the application of the stimuli. </li></ul><ul><li>The pain continues for hours or days after removal of the stimuli. </li></ul><ul><li>Is associated to cutaneous and deep tissues. </li></ul><ul><li>Is transsmitted by C fibers </li></ul>
  9. 9. PAIN <ul><li>THE PAIN SENSORY SYSTEM </li></ul><ul><li>DEFINITIONS </li></ul><ul><li>Nociceptors: </li></ul><ul><ul><li>Specialized sensory receptors that provide information about tissular damage </li></ul></ul><ul><ul><li>Are “free nerve endings”, localized at the skin, underlying tissue and visceras </li></ul></ul><ul><ul><li>Nociceptors are the least differentiated of the sensory receptors, there are two types: Thermal or Mechanical & polymodal </li></ul></ul>
  10. 10. PAIN <ul><li>THE PAIN SENSORY SYSTEM </li></ul><ul><li>DEFINITIONS </li></ul><ul><li>Nociceptors: </li></ul><ul><ul><li>There are two types: </li></ul></ul><ul><ul><ul><li>Thermal or mechanical, associated with fast, sharp pricking pain transmitted on small diameter, thinly myelinated A-Delta fibers) Release excitatory amino-acid-glutamate (Fast EPSP) </li></ul></ul></ul><ul><ul><ul><li>Polymodal nociceptors, activated by variety of high intensity mechanical & thermal stimuli, transmitted slowly on small unmyelinated C fibers, release excitatory aminoacid-glutamate and neuropeptides (Substance P = slow EPSP) </li></ul></ul></ul>
  11. 11. Substances & effects on nociceptors <ul><li>SUBSTANCES </li></ul><ul><ul><li>Potassium </li></ul></ul><ul><ul><li>Bradykinin </li></ul></ul><ul><ul><li>Substance P </li></ul></ul><ul><ul><li>Serotonin </li></ul></ul><ul><ul><li>Histamine </li></ul></ul><ul><ul><li>Prostaglandins </li></ul></ul><ul><ul><li>Leukotrienes </li></ul></ul><ul><li>EFFECTS </li></ul><ul><ul><li>Activation </li></ul></ul><ul><ul><li>Activation & sensitization </li></ul></ul><ul><ul><li>Sensitization </li></ul></ul><ul><ul><li>Activation </li></ul></ul><ul><ul><li>Activation </li></ul></ul><ul><ul><li>Sensitization </li></ul></ul><ul><ul><li>Sensitization </li></ul></ul>
  12. 12. Substances & effects on nociceptors <ul><li>SUBSTANCES </li></ul><ul><ul><li>Bradykinin </li></ul></ul><ul><ul><li>Substance P </li></ul></ul><ul><ul><li>Histamine </li></ul></ul><ul><li>EFFECTS </li></ul><ul><ul><li>Most potent pain produced agent </li></ul></ul><ul><ul><li>Vasodilator & Release Histamine </li></ul></ul><ul><ul><li>Activates polymodal nociceptors </li></ul></ul>
  13. 13. PAIN <ul><li>DEFINITIONS </li></ul><ul><li>Hyperalgesia: </li></ul><ul><ul><li>Is the lowering of the threshold level of the nociceptors, after noxius stimuli is applied and there is tissular damage. </li></ul></ul><ul><ul><li>There is increased sensation of pain with subsequent stimuli </li></ul></ul><ul><li>Is divided into: </li></ul><ul><ul><li>Primary: occurs at the site of tissue damage </li></ul></ul><ul><ul><li>Secondary: increased sensitivity at the surrounding undamaged tissue </li></ul></ul>
  14. 14. PAIN <ul><li>DEFINITIONS </li></ul><ul><li>Primary hyperalgesia mechanism </li></ul><ul><ul><li>Repetitive heating: reduces threshold of C & Alfa nociceptors </li></ul></ul><ul><ul><li>Repetitive mechanical stimuli: sensitize nearby nociceptors </li></ul></ul><ul><ul><li>Changes in synaptic efficacy of afferent fibers at spinal cord or C.N.S. </li></ul></ul>
  15. 15. PAIN <ul><li>DEFINITIONS </li></ul><ul><li>Secondary hyperalgesia mechanism </li></ul><ul><ul><li>Sensitization of nociceptors with diffuse collateral branches, one of which innervates the site of injury </li></ul></ul><ul><ul><li>Sensitization of central nociceptors as a result of sustained activation </li></ul></ul><ul><ul><li>Suggested CNS facilitation of incoming pain stimuli </li></ul></ul>
  16. 16. PAIN <ul><li>NOCICEPTOR-INDUCED INFLAMMATION </li></ul><ul><li>Released Substance P actions </li></ul><ul><ul><li>Potent vasodilation </li></ul></ul><ul><ul><li>Degranulation of mast cells </li></ul></ul><ul><ul><li>Chemotaxis to leukocytes </li></ul></ul><ul><ul><li>Increase production and release of inflammatory mediators </li></ul></ul><ul><ul><li>Induces neurogenic formation </li></ul></ul>
  17. 17. PAIN <ul><li>Pain ascending pathways. </li></ul><ul><ul><li>Nociceptor </li></ul></ul><ul><ul><li>Pain fibers: </li></ul></ul><ul><ul><ul><li>A-Delta fibers </li></ul></ul></ul><ul><ul><ul><li>C Fiber </li></ul></ul></ul><ul><ul><li>Spinal cord relays </li></ul></ul><ul><ul><ul><li>Lamina I & II (Substantia gelatinosa) </li></ul></ul></ul><ul><ul><ul><li>Synapsis to spinal neurons </li></ul></ul></ul><ul><ul><li>Spinal neurons receives convergence imputs from many primary afferents. Upper and lower spinal cord level (Important for “refered pain”) </li></ul></ul><ul><ul><li>Spinal neurons send axons to contralateral spinothalamic tract </li></ul></ul>
  18. 18. PAIN <ul><li>Pain ascending pathways. </li></ul><ul><ul><li>Spinal cord relays send axons to contralateral spinothalamic tract </li></ul></ul><ul><ul><li>Spinothalamic tract axons connect to Thalamic neurons </li></ul></ul><ul><ul><li>Thalamic neurons projet to somatosensory cortex and cingulate gyrus and frontal lobe (Emotional responses) </li></ul></ul>
  19. 19. Substances & effects at the spinal cord Inhibition Substantia gelatinosa Opioids Excitatory C fibers Substance P Excitatory A delta & C fibers Glutamate Effects on pain transmition Main location or source Substance
  20. 20. PAIN <ul><li>WHY THE DIFFERENT INDIVIDUAL RESPONSES TO THE SAME NOXIOUS STIMULI OR TISSULAR DAMAGE?? </li></ul><ul><li>Pain threshold is the same for everybody </li></ul><ul><li>The “Analgesia” system is involved in this individual response </li></ul><ul><li>It “modulates” (Increase or decrease) and sometimes suppress completely the transmition of the noxious stimuli </li></ul>
  21. 21. PAIN <ul><li>ANALGESIA SYSTEM </li></ul><ul><ul><li>SUPRASPINAL ANALGESIA SYSTEM </li></ul></ul><ul><ul><ul><li>Periaqueductal Gray matter Opioids </li></ul></ul></ul><ul><ul><ul><li>Raphe magnus nucleus Serotonin </li></ul></ul></ul><ul><ul><ul><li>Nucleus Paragiantocellularis Nor-epinephrine </li></ul></ul></ul><ul><ul><li>Send the Dorsolateral funiculus that end at the dorsal horn of the spinal cord </li></ul></ul>
  22. 22. PAIN <ul><li>SPINAL ANALGESIA SYSTEM </li></ul><ul><ul><li>Dorsolateral funiculus; </li></ul></ul><ul><ul><ul><li>Is a descending tract that end at the dorsal horn of the spinal cord inhibiting ascending spinothalamic projection neurons </li></ul></ul></ul><ul><ul><ul><li>Directly releases serotonin and nor-epinephrine </li></ul></ul></ul><ul><ul><ul><li>Indirectly through enkephalin interneurons in the dorsal horn </li></ul></ul></ul><ul><ul><ul><ul><li>Local opioids </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Gate control theory </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Wide Dinamic Range Neurons </li></ul></ul></ul></ul>
  23. 23. PAIN <ul><li>Special considerations on pain </li></ul><ul><li>Refered pain: </li></ul><ul><ul><li>Is the pain that arises from nociceptors in deep visceral structures, but is felt at sites on the body surface, sometimes remote areas </li></ul></ul><ul><ul><li>Examples: </li></ul></ul><ul><ul><ul><li>Myocardial infarction pain </li></ul></ul></ul><ul><ul><ul><li>Esophageal diseases </li></ul></ul></ul><ul><ul><ul><li>Gall bladder disease </li></ul></ul></ul><ul><ul><ul><li>Apendicitis </li></ul></ul></ul><ul><ul><ul><li>Gastric diseases </li></ul></ul></ul>
  24. 24. PAIN <ul><li>Special considerations on pain </li></ul><ul><li>Deafferentation pain (Nerve elongation) </li></ul><ul><li>Limb phantom pain (Amputation) </li></ul><ul><ul><li>Proposed mechanism: </li></ul></ul><ul><ul><ul><li>Loss of afferent input </li></ul></ul></ul><ul><ul><ul><ul><li>plus </li></ul></ul></ul></ul><ul><ul><ul><li>Hyperactivity of dorsal neurons </li></ul></ul></ul>
  25. 25. PAIN <ul><li>Special considerations on pain </li></ul><ul><li>Sympathetically maintained Pain </li></ul><ul><li>“ Causalgia” </li></ul><ul><li>Chronic pain after peripheral nerve injury, accompanied by swelling of the extremity, periarticular osteoporosis, and arthritic changes in the distal joints. </li></ul><ul><li>Pathophysiology is poorly understood </li></ul><ul><li>Rapid pain relief could be achived by blocking sympathetic nervous system </li></ul>
  26. 26. PAIN <ul><li>TREATMENT </li></ul><ul><li>Peripheral analgesics </li></ul><ul><ul><li>Acetaminophen </li></ul></ul><ul><ul><li>Aspirin </li></ul></ul><ul><ul><li>Non-steroidal Anti-inflammatory NSAIDs </li></ul></ul><ul><ul><ul><li>COX 2 selective drugs (Rofecobix, celecobix) </li></ul></ul></ul><ul><ul><ul><li>Ketorolac </li></ul></ul></ul>
  27. 27. PAIN <ul><li>TREATMENT </li></ul><ul><li>Central analgesics </li></ul><ul><ul><li>Opioids: </li></ul></ul><ul><ul><ul><li>Orally </li></ul></ul></ul><ul><ul><ul><li>Sublingual </li></ul></ul></ul><ul><ul><ul><li>Transdermal </li></ul></ul></ul><ul><ul><ul><li>Parenteral </li></ul></ul></ul><ul><ul><ul><li>Intra-spinal </li></ul></ul></ul><ul><ul><li>Chronic use of opioids </li></ul></ul><ul><ul><li>Patient controled analgesia (PCA) </li></ul></ul>
  28. 28. PAIN <ul><li>TREATMENT </li></ul><ul><li>Antidepresant drugs </li></ul><ul><ul><li>Tricyclic </li></ul></ul><ul><li>Anticonvulsant </li></ul><ul><ul><li>Fenitoin </li></ul></ul><ul><ul><li>Carbamazepine CBZ </li></ul></ul><ul><ul><li>Gabapeptin </li></ul></ul><ul><li>Antiarrhythmic </li></ul><ul><ul><li>Lidocaine </li></ul></ul><ul><ul><li>Mexiletine </li></ul></ul>