WEEK 4 - Pain & Analgesia, Opioids, and Anaesthesia & Anaesthetics

Question 1

What is pain?

Answer 1

“An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’.

Question 2

Briefly explain the Biopsychosocial model of pain…

(The factors influencing pain)

Answer 2

Biology:
Gender, physical illness, disability, genetic vulnerability, immune function, neurochemistry, stress reactivity, and medication effects.

Social Context:
Social supports, family background, cultural traditions, social / economic status, and education.

Psychology:
Attitudes / beliefs, learning / memory, personality, behaviours, emotions, coping skills, past trauma.

Question 3

What is the purpose of acute pain?

Answer 3

Acute pain is protective, warms of harmful stimulus, and provokes a movement away from the harmful stimulus.

Question 3

What are the different steps of pain processing?

Answer 3

1) Detection
2) Transmission
3) Perception
4) Descending Modulation

Question 4

Explain the process of Detection…

Answer 4

1) Detection:
Nocioceptors - sensory neurons that detect noxious stimuli.

Peripheral Sensitisation;
- increased responsiveness of nerves to pain.
- sensitising agents make it more liekly the action potentials will be generated.
- important to ensure early detection of a harmful stimulus.

Question 5

Explain the process of Transmission….

Answer 5

2) Transmission:
- Influx of Ca^2+ through voltage gates channels in presynaptic membrane.
- Release of vesicles containing glutamate (excitatory CNS neurotransmitter) and neuropeptides.
- Promotes action potentials in secondary relay neuron.

Central Sensitisation;
- Enhanced excitability of central synapses.
- Due to intense / sustained activation of central transmission leading to opening of NMDA channels. (Causes Ca2+ influx activating kinases leading to the phosphorylation of AMPA, NMDA, and gene regulatory proteins.)

Regulation of Transmission:
- Major inhibitory neurotransmitters are; Opioid peptides, Noradrenaline, GABA (inhibitory neurotransmitter), and Serotonin.
- Overal effects; inhibit activation of presynaptic Ca2+ channels, and decrease post synaptic membrane potential.

Question 6

Explain the process Central Perception…

Answer 6

3) Central Perception:
- Nocioception (detection of noxious stimulus is a neural process).
- Pain perception is a subjective experience; involves multiple areas of the brain, and influenced factors including biology, psychology, and social contexts.

Question 7

Describe the differences between Acute and Chronic pain….

Answer 7

Acute Pain:
- Rapid onset
- Protective
- Identifiable cause
- Limited duration
- Tends to get better

Chronic Pain:
- > 3 months duration
- No biological function
- Cause not always identifiable
- Unpredictable duration
- Doesn’t get better
- Emotional component

Question 8

What are the different pathological types of pain?

Answer 8

1) Clinical Nocioceptive pain:
- Damage to the tissues

2) Neuropathic pain:
- Damage to the nerves

3) Psychogenic Pain:
- Stress / Anxiety

Question 9

Explain Clinical Nociceptive Pain…

Answer 9

• Damage ti the tissues reported to the brain by the NS.
• Acute (e.g. cuts, burns, surgery, childbirth).
• Chronic (e.g. chronic inflammatory conditions such as rheumatoid arthritis).
• Contains Visceral and Somatic types.

Visceral (e.g. internal organs, poorly localised, dull, achy, associated with nausea, vomiting and sweating. Arises from distension, inflammation, ischaemia).
Somatic (e.g. superficial [skin] OR deep [muscles, joints, bones, and tendons]. Localised, sharp, and arises from cutting a finger or stretching a muscle etc.)

Question 10

Explain Psychogenic Pain….

Answer 10

• Caused by psychological factors.
• Usually occurs due to tissue / nerve damage, but increases and is prolonged because of stress, fear, anxiety, or depression.

Question 10

Explain Neuropathic Pain….

Answer 10

• Dysfunction / damage to the nerves spinal cord, or brain.
• Characterised by a burning, tingling, or stabbing sensation.
• Likely to be persistent (nerves have poor capacity to heal, injury leads to changes in sensitivity, and continued perception of injury).

Damage to nerve cells can induce…
- loss of function.
- spontaneous pain
- increased sensitivity
- combination of above.

Inflammation leads to altered gene expression:
- changes in Na+ channel expression.

Question 10

Explain Persistant Pain….

Answer 10

Sensitisation occurs; peripheral or central.

Can lead to:
- Hyperalgesia (increased pain from a stimulus that normally provokes pain).
- Allodynia (pain due to a stimulus that doesnt normally provoke pain (e.g. light)).

It is important to treat pain otherwise it can get worse!

Question 11

What is Analgesia?

Answer 11

• Absence of pain in response to stimulation which would normally be painful.
• Analgesics provide relief from pain.

Classes of drug with analgesic effects include:
- Paracetamol
- NSAIDs
- Opioid Agonists
- Anaesthetics

Adjuvant analgesics include:
- Anti-depressants
- Ant-coagulants
- NMSA receptor antagonists
- Clondine
- Medicinal cannabis

Question 12

What can you tell me about Paracetamol?

MOA? ADRs? Overdose?

Answer 12

Also called Acetaminophen (USA).

Analgesic properties:
- for mild / moderate pain.
- has antipyretic effect.

MOA is not fully understood however can assume:
- inhibition of central COX.
- activation of endocannibinoid system.
- spinal serotonergic pathways.
[seems to have central and peripheral effects]

ADRs:
- very few at normal dose.
- main issue is hepatotoxicity with overdose.

Overdose:
- Leads to formation of NAPQI - causing hepatotoxicity.