Pain and general drugs

Question 1

Difference between nociception and pain

Answer 1

NOCICEPTION = the neural processing of pain without the emotional effects/stimulus

PAIN= An unpleasant sensory and emotional experience resulting from potential or actual tissue damage

Question 2

Define convergence

Answer 2

A single sensory neurone within CNS can reveive inputs from many peripheral receptors

Question 3

Transduction mechanism in pain

Answer 3

• Deformation of membrane
• K+ and na+ channels open
• Receptor potential
• Ap propogated to CNS

Stronger stimulus; stronger receptor potetntial; greater number and frequency of APS

Question 4

C fibre characteristics

Answer 4

• unmyelinated fibres
• slow conduction velocity
• terminate in superficial lamina I-II of dorsal horn
• Responses sensitive to glutamate receptor

Question 5

Allodynia

Answer 5

Non-painful stimulus perceived as painful

Question 6

Hyperalgesia

Answer 6

Painful stimuli becomes more painful

Question 7

Which part of thalamus is pain relayed to

Answer 7

Ventral posterior nucleul

Question 8

Through which structures does the inhibitory pathway for pain run

Answer 8

PAG

NRM

SPinal cord

Question 9

Substance that blocks effect of morphine

Answer 9

Naloxene

Question 10

Normal neuronal transmission

Answer 10

• AP causes voltage gates ca2+ channels to open which bind to vesicles containing NT
• Vesicles migrate and fuse with membrane, releasing NT
• If enough NT binds post-synaptically and exceeds threshold; AP

Question 11

Neuronal transmission inhibition by opioid

Answer 11

1. Activated G_i; decreases cAMP via decreased AC; alters protein kinases, influences excitability
2. Opening/closing of ion channels
   
   • Closure of Ca channel: no Ca can enter, vesicles cant release NT
   • Increase K+ efflux: Lowers membrane potential; hyperpolarisation i.e. less excitable

Post-synaptic K channels can also be affected in same manner

Question 12

Effect of sustained morphine exposure

Answer 12

Tolerance

Uncoupling of G-protein; lowered effect

Dependence

Question 13

Importance of m-opioid receptor location within spinal cord

Answer 13

STT mainly synapses with C fibres in superifical lamina of dorsal horn, whilst AB fibres synapse more deeply. Since the opioid receptors also are superficially placed tactile pathways arent affected too much

Question 14

How do opioids effect descending inhibitory control of pain

Answer 14

Receptors also at PAG and NRM

Question 15

limitation of opioid treatment in neuropathic pain

Answer 15

In neuropathic pain both A/C fibres are involved. C drives hyperalgesia. A fibres produce pain state known as allodynia; pain from stimulus not normally painful

• Hard to treat with analgesics due to lack of opioid receptors on A-fibres, only treats hyperalgesia
  
  • Can use Pregab

Question 16

Characteristics of Dia-morphine

Answer 16

Higher lipophilicity - rapid brain penetration

Broken down to morphine in CNS

More potent and addicitve than morphine

Question 17

COX 1 vs COX 2

Answer 17

COX1

• Constitutive enzyme; always expressed in most tissues and platelets
• Involved in normal homeostasis
• Generally wan’t to keep unaltered in treatment

COX2

• Induced in activated inflammatory cells following tissue damage
• Enzyme responsible for production prostaglandins from arachadonic acid

Question 18

Which cells release PGD₂

Answer 18

Normally mast cells

In chronic inflammation also monocytes and macrophages can release PG2/TXA2

Question 19

PGE2, PGI2 and PGD2 effect on inflammation

Answer 19

Powerful vasodilators. Increased blood flow to site of inflammation and increased leakiness of vessels. Synergise with histamines to cause itch and bradykinin to cause pain

Question 20

Effect of Bradykinin in inflammation

Answer 20

• Synthesised de novo during damage
• Activated nociceptiors by B1 and B2 G-protein coupled receptors
• Increases PG production, reinforces PG response
  
  • PG enhance nociceptors response to BK, vicious circle

Question 21

Define antipyretic

Answer 21

Reduces fever

Body temp regulated by hypothalamus. NSAIDs reset the thermostat by blocking effect of PGs on hypothalamus

Question 22

Aspirin mode of action

Answer 22

Irreversible inhibition of COX1 and 2

Question 23

Anasthesia is an insensitivity to pain following suppression of:

Answer 23

• Afferent sensory reflex - Local/regional anesthesia
• Central neural processing - general anesthesia

Question 24

Local anaesthetic - mode of action

Answer 24

• Block na+ channels; AP not going to brain about pain
• Administered as a weak base or uncharged/lipid soluble molecule for cell entry
• Often given with vasoconstrictor e.g. adrenaline to enhance the duration of drug by causing partial ischaemia to area

Question 25

Spinal/regiona laneasthesis-procedure

Answer 25

• Local anaesthetic e.g. lidocaine given to numb area of injection
• Locate L4
• Rapid block of nerve roots below?

Question 26

examples of intravenoues General anaesthtics

Answer 26

• Barbiturates e.g. thiopental, methohexital
• Non-brabiturates: propofol, etomidate, midazolam, ketamine

Question 27

Examples of inhaled general anaesthetics

Answer 27

• Volatile liquids e.g. halothane
• Inorganic gases e.g. NO

Question 28

SEEEEEE last half of lecture on anaesthetics