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 Segmental Organization 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