Pharmacology of Pain 1

Question 1

Pain

Answer 1

• The coupling of an unpleasant stimulus and conscious perception and an emotional response

Question 2

Nociception

Answer 2

• Sensation of an unpleasant stimulus

Question 3

Nociceptors

Answer 3

• Free nerve endings distributed throughout the body which detect nociceptive stimuli

Question 4

peripheral nerves:

Sensory Afferent:

A-fiber

Answer 4

• Large myelinated nerves, rapid conduction
• ADelta - nociception
  
  • “First” Pain, well localized

Question 5

Peripheral Nerves

Sensory Afferent

C-fiber

Answer 5

• unmyelinated, slow conducting
  
  • “Second” pain
    
    • dull
    • aching
    • Poorly localized

Question 6

Neurotransmitters and receptors:

Stimulatory receptors:

Glutamate:

AMPA receptor

Answer 6

• Primary receptor for transmitting pain
• Receptors are located throughout the brain, not specific for pain
• Most common receptor in the brain

Question 7

Neurotransmitters and Receptors:

Stimulatory Receptor:

Glutamate:

NMDA receptor

Answer 7

• Normally quiescent, but subsequently activates enhancing pain stimulus and depresses activation threshold

Question 8

Neurotransmitters and Receptors:

Stimulatory Receptor:

Complementary pathways:

Answer 8

Prostaglandin E2

Neurokinin receptors - Sunstance P

Transient receptor potential vanilloid receptor

Spinal Supraspinal

Question 9

Neurotransmitters and Receptors:

Inhibitory Receptors:

Answer 9

• Opiate:
  
  • spinal and supraspinal
• GABA:
  
  • peripheral, spinal, and supraspinal
• Serotonin:
  
  • some inhibit pain transmission, some enhance pain transmission
  • Analgesia, spinal and supraspinal
• Alpha-2
  
  • binds presynaptically to decrease neurotransmitter release:
    
    • spinal and supraspinal

Question 10

Neurotransmitters and Receptors:

Sodium Channel Blocker

Answer 10

• Local Anesthetics
• Directly suppress / inhibits nerve depolarization
• Actually can stop pain transmission as opposed to modulating transmission
• Peripheral nerve blocks, spinal nerve blocks

Question 11

Sensitization

Answer 11

• Stimulus which is normally innocuous becomes a nociceptive stimulus
  
  • or a mildly painful stimulus results in moderate or severe pain
• Sunburn slap
• Chronic pain

Question 12

Sensitization:

Peripheral

Answer 12

• Reduction in nociceptor activation thresholds
• Decrease tissue pH, cytokines, bradykinin, serotonin, histamine, ATP, prostaglandins, leukotrienes

Question 13

Sensitization:

Central

Answer 13

• N-methyl-d-aspartate (NMDA) receptor activation
  
  • Increase in magnitude and response of stimulus
  • Reduction in activation threshold of nociceptors
• Decreased endogenous opiods
• Desensitization of opiate receptors
• Neurokinin receptor activation
• Others

Question 14

Opiate

Answer 14

compound derived from the opium plant

Question 15

Opiod

Answer 15

Endogenous peptide or synthetic compound interacting on opiate receptors

Question 16

Opiate Receptor Activation:

Answer 16

• Decrease voltage gated Ca++ currents
  
  • decrease inward flow
  • Decrease stimulatory NT release
• G-protein inhibition of Adenylyl cyclase
  
  • Decrease cAMP
  • Increase receptor linked K+ currents
    
    • Increase outward flow
    • Hyperpolarization
      
      • harder to depolarize and transmit the pain signal