NRSC/SP H 282

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 gt respond to mechanical, chemical or
  thermal stimulation
• High threshold mechanical nociceptors gt 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 leaksrunny 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 gt nearly all forms of stimulation can
  result in pain
• Teeth gt 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