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NRSC/SP H 282

NRSC/SP H 282. October 9, 2006 PAIN. Step on a thumbtack?. Need for Pain. Short latency - warn the organism that it is in danger so it will alter the situation (e.g., withdraw limb, take flight, respond with defensive maneuver).

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NRSC/SP H 282

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  1. NRSC/SP H 282 October 9, 2006 PAIN

  2. Step on a thumbtack?

  3. Need for Pain • Short latency - warn the organism that it is in danger so it will alter the situation (e.g., withdraw limb, take flight, respond with defensive maneuver). • Long latency - immobilize the organism so that recovery from injury can occur.

  4. Pain Stimuli & Receptors • Stimuli are mechanical, chemical or thermal. • Receptors are called nociceptors (from Latin, nocere – to hurt). • Polymodal => respond to mechanical, chemical or thermal stimulation • High threshold mechanical nociceptors => respond primarily to intense mechanical stimulation

  5. Pain Stimuli & Receptors • Two general types of nociceptors are characterized by where they are found and the neurons associated with them. The neurons are usually small, and slow-conducting. • A fibers wrapped in Schwann cells and found in the skin • C fibers originating in fat layers of skin (polymodal) and in muscles and joints (sometimes called III, IV)

  6. Pain Mediators • Tissue injury causes release of chemicals • They sensitize or activate receptors • Neurons release substance P, which stimulates mast cells and blood vessels • Histamine released from mast cells and bradykinin released from blood vessels add to pain stimulus

  7. Substance P • Neurotransmitter that is released by a nociceptor axon and results in vasodilation (swelling of blood capillaries). • It causes mast cells to release histamine, which contributes to swelling and “inflammation.”

  8. Bradykinin • Bradykinin is a byproduct of the breakdown of material (kininogen) found in the extraceullar spaces. It can directly stimulate the pain receptors (i.e., causes neurons to depolarize).

  9. Histamine • Produced by mast cells, histamine can bind to nociceptor membranes and cause depolarization. • It also causes blood capillaries to become “leaky,” leading to swelling, inflammation at the site of injury. • (We use antihistamines to reduce pain and swelling or to counteract upper respiratory system leaks…runny noses.)

  10. Adequate stimuli for nocicepton • Cutaneous receptors detect stimuli from surrounding environment - cuts, burns, freezing; • Muscle receptors detect mechanical injury, spasm, cramping and ischemia; • Visceral stimuli include distension, ischemia, inflammation, spasm and traction.

  11. Special sites • Cornea => nearly all forms of stimulation can result in pain • Teeth => similar to cornea in terms of temperature and pressure sensitivity

  12. Pathways for Pain vs. Tactile

  13. Spino-thalamic pathway

  14. Reminder of SegmentalOrganization • The Spinal cord • Sensory Organization of the spinal cord • Divisions • Cervical (C) • Thoracic (T) • Lumbar (L) • Sacral (S)

  15. Dermatomes & Cortical Representation

  16. Comparison of touch/pressure and pain pathways

  17. MEASUREMENT OF PAIN • RECORDING FROM SINGLE NEURONS, USUALLY IN ANESTHETIZED ANIMALS • PSYCHOPHYSICAL PROCEDURES IN HUMAN VOLUNTEERS INVOLVING • SCALING OF SENSATION OR • CROSS MODALITY MATCHING

  18. EXAMPLE OF NEURON RESPONSE • Studies of single neurons help to unravel the puzzle of nociceptor action

  19. Temperature • Thermoreceptors • “Hot” and “cold” receptors • Varying sensitivities

  20. CONTROL OF PAIN • GATE THEORY OF PAIN • “LOCAL” ANESTHESIA • NSAID, OPIODS • CNS CONTROL OF PAIN • ACUPUNCTURE - PLACEBO?

  21. GATE THEORY Example: gentle pressure on a fresh injury may help reduce pain

  22. LOCAL ANESTHESIA • LIDOCAINE - SYNTHETIC VERSION OF COCAINE • TOPICAL - APPLIED TO MEMBRANES • INFILTRATION - INJECTED NEAR NEURONS • INFUSED INTO CEREBROSPINAL FLUID - SPINAL (cf pg 95 in your text) • MECHANISM – BLOCKS SODIUM CHANNELS IN NEURONS. NO SODIUM, NO ACTION POTENTIAL!

  23. Capsaicin (Chilies) and Pain • Capsaicin generates its heat in the mouth by causing the release of substance P from nociceptors in the mouth. • In large quantities, it depletes substance P from nerve terminals and can bring relief from pain (e.g., with shingles).

  24. NSAIDs/OPIOIDs/Endorphins • Nonsteriodal anti-inflammatory drugs • e.g., salicylates, inhibit the creation of the enzymes needed to create prostaglandin (chemical mediator for pain) • Opiods • e.g., morphine, oxycodone, codeine – mechanisms poorly understood • Endorphins • naturally manufactured by brain, they may block peripheral transmitters or hyperpolarize neurons

  25. DESCENDING CONTROL • Midbrain structures may modulate or control dorsal horn transmission of ascending tracts

  26. ACUPUNCTURE • Derived from India • Practiced in China for 5000 years • Used in veterinary medicine • NIH consensus statement 1998

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