Opioids and Pain

Question 1

Nociception

Answer 1

The physiological processes in response to a noxious stimulus
Very immediate
Activates particular sensory nerve

Question 2

Allodynia

Answer 2

Pain in response to a normally innocuous stimulus

Question 3

Hyperalgesia

Answer 3

Enhanced pain to a normally painful stimulus

Question 4

Nociceptive Pain

Answer 4

Direct activation of nociceptors by noxious stimuli

Ex: touching something hot

Question 5

Inflammatory Pain

Answer 5

Activation by inflammatory mediators

Ex: rheumatoid arthritis

Question 6

Neuropathic Pain

Answer 6

Pain arising from nerve damage
Ex: Postherpetic neuralgia
Patient looks normal, but damage to nervous system causes extreme pain

Question 7

Opiate

Answer 7

Drug derived from opium

Question 8

Opioid

Answer 8

Agents with opiate-like actions
- synthetic drugs
- proteins that mimic opiate actions
(endorphins)

Question 9

Narcotic

Answer 9

2 Definitions

1. Sleep inducing (Pharmacological)
2. Drugs producing dependence (Legal)

Question 10

During acute inflammation…

Answer 10

Upregulation of opioid receptors

Opioid analgesia very effective

Question 11

During chronic inflammation…

Answer 11

Downregulation of opioid receptors

Opioid analgesia less effective

Question 12

Negative Side Effects of Opioids

Answer 12

Severe constipation, somnolescence, cardiorespiratory depression
Tolerance
Dependence (Addiction)

Question 13

Physical Dependence

Answer 13

Drug withdrawal produces physical abstinence syndrome:
Mild: lacrimation, sweating, yawning
Severe: anorexia, cramps, nausea, vomiting, restlessness, irritability, tremor, HR/BP changes, chills, spasms, PAIN

Question 14

Psychological Dependence

Answer 14

Compulsive drug seeking behaviour
Occurs with drugs with mood enhancing properties
Activates dopaminergic circuits (endogenous reward systems)

Question 15

Treatment of Dependence

Answer 15

Cessation of drug intake
Naltrexone (μ-antagonist)
Methadone (μ-agonist – good oral availability (no more injections), selective, long-lasting/slow withdrawal

Question 16

Peripherally restricted opioids

Answer 16

Can target pain at the source
Reduce sensitization of nociceptors
Do not pass the blood brain barrier therefore less likely to cause addiction issues, centrally-mediated side-effects (e.g. respiratory depression)

Question 17

How to improve opioid receptor levels

Answer 17

Inhibit β-arrestin activity = reduced receptor internalization
Inhibit receptor degradation (protease inhibitors)
Promote receptor recycling

Question 18

4 Opioid receptor subtypes and their function

Answer 18

Mu, kappa delta (inhibit neuronal depolarization)

NOP (neuronal depolarization

Question 19

2 Ways to reduce pain transmission

Answer 19

1. On presynaptic nerve terminal: opioid binds, reduces release of excitatory NTs and reduce Ca input which feeds back into inhibition of release
2. On postsynaptic nerve terminal: increase K permeability (hyperpolarization)