NRSC/SP H 282
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Transcript of NRSC/SP H 282
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NRSC/SP H 282
October 9, 2006
PAIN
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Step on a thumbtack?
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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.
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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
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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)
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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
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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.”
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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).
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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.)
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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.
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Special sites• Cornea => nearly all forms of stimulation can
result in pain
• Teeth => similar to cornea in terms of temperature and pressure sensitivity
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Pathways for Pain vs. Tactile
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Spino-thalamic pathway
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Reminder of Segmental
Organization• The Spinal cord
– Sensory Organization of the spinal cord
• Divisions– Cervical (C)– Thoracic (T)– Lumbar (L)– Sacral (S)
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Dermatomes & Cortical Representation
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Comparison of touch/pressure and pain pathways
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MEASUREMENT OF PAIN
• RECORDING FROM SINGLE NEURONS, USUALLY IN ANESTHETIZED ANIMALS
• PSYCHOPHYSICAL PROCEDURES IN HUMAN VOLUNTEERS INVOLVING– SCALING OF SENSATION OR– CROSS MODALITY MATCHING
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EXAMPLE OF NEURON RESPONSE
• Studies of single neurons help to unravel the puzzle of nociceptor action
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Temperature
• Thermoreceptors– “Hot” and “cold” receptors– Varying sensitivities
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CONTROL OF PAIN
• GATE THEORY OF PAIN
• “LOCAL” ANESTHESIA
• NSAID, OPIODS
• CNS CONTROL OF PAIN
• ACUPUNCTURE - PLACEBO?
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GATE THEORY
Example: gentle pressure on a fresh injury may help reduce pain
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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!
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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).
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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
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DESCENDING CONTROL
• Midbrain structures may modulate or control dorsal horn transmission of ascending tracts
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ACUPUNCTURE
• Derived from India
• Practiced in China for 5000 years
• Used in veterinary medicine
• NIH consensus statement 1998