PAIN AND OPIOIDS Flashcards

(25 cards)

1
Q

What is pain?

A
  • Induced in response to tissue damage
  • Due to mechanical or chemical stimulation
  • Muscoskeletal/ rheumatic pain and neuropathic pain are the most common form
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2
Q

Physiological pain

A

Protects from danger by giving warning about tissue damage

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3
Q

Inflammatory pain

A

Tissue damage releases pain mediators which cause inflammation and temporary hypersensitivity
- Also cause allodynia and hyperalgesia

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4
Q

Neuropathic pain

A

Somatosensory nervous system lesions which cause permanent hypersensitivity and pain doesn’t subside
- Also cause allodynia and hyperalgesia

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5
Q

Allodynia and hyperalgesia

A

Non noxious stimuli which evokes pain and wouldn’t normally do this is allodynia

Hyperalgesia is a noxious stimula which evokes pain

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6
Q

Pain pathway

A
  • Bipolar neutrons has two projections - one in superficial layer and one in peripheral
  • Activates peripheral nociceptors
  • Cell body found in dorsal root ganglia
  • Substance P and Glutamate activate Neuron and transmit pain information
  • information from both spinal cord reaches the sensory cortex via the thalamus
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7
Q

Synaptic endings

A

Packed with pain receptors as well as histamine and serotonin receptors
ATP also acts as a neurotransmitter for purinergic receptors - P2X3
- Tissue damage causes cell death and the release of its content which consists of a lot of ATP

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8
Q

Bipolar neurons

A
  • Carry pain information from periphery to dorsal horn

- Three different neurons carry this information: C-fibre, Abeta-fibre and Adelta-fibre

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9
Q

C fibre

A
  • Unmyelinated
  • Carry stimulation from skin, deeper tissue and muscle
  • Are thermoceptors, mechanoceptors and nociceptors
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10
Q

A beta fibres

A

Myelinated and carry information of low intensity stimuli - for example during allodynia
- Are mechanoceptors

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11
Q

A delta fibres

A
  • Myelinated
  • Allow transmisson of sharp sensations and acute pain
  • Mechanoceptors and nociceptors
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12
Q

Gate control theory

A

Substantia gelatinosa packed with small inhibitory neurons

  • Extend from SG to synapse
  • Activated by pain stimulation in spinal cord
  • Takes place in order for pain to subside
  • A beta fibres activate SG
  • GABA and opioids are inhibitory neurotransmitters
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13
Q

Descending pathways

A
  • Inhibit transmission of pain information
  • Neuron from dorsal horn acts on neurons in raphe nucleus of brain which get activated by 5-HT
  • Enkephalin neurons run to dorsal horn and block pain transmission
  • PAG area of brain contains opioid receptors which activate neurons in raphe nucleus activating descending inhibitory neurons
  • NAergic neurons from locus coeruleus directly to dorsal horn release noradrenaline which blocks pain
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14
Q

Activation of bipolar neurons

A
  • Packed with nociceptors
  • Binding of glutamate or substance P opens Na+ channel
  • Contains sodium and potassium channels in order to depolarise the neuron
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15
Q

Neuropathic pain

A

Caused by lesion of somatosensory nervous system I.e. diabetes, stroke, MS, aging, major surgery/trauma

  • Hyperexcitability of bipolar neuron causes release of substance P and glutamate which activate receptors
  • Na+ and Ca2+ influx causes depolarisation
  • Hyperexcitation causes endocytotoxicity causing cell death and further lesions
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16
Q

Plasticity/hyperpolarisation

A
  1. ) Activation - NMDA receptor sensitised
  2. ) Modulation - phosphorylation of NMDA receptor due to constant glutamate release and continuous receptor activation
  3. ) Modification - Gene expression altered and release of NT increases or decreases. Altered sensory nerve phenotype causing change from C fibre to A fibre
17
Q

Pharmacotherapy for neuropathic pain

A
  1. ) TCA’s (tricyclic antidepressants) e.g amitryptiline which inhibits NA reuptake
  2. ) Anti-epileptic e.g Carbamazepine which acts on voltage-gated Ca2+ channel reducing excitibilaty of sensory neuron
  3. ) Anti-epileptic e.g. Gabapentin and Pregabalin which binds to alpha 2 delta subunit of L-type voltage- gated ca2+ channel reducing Ca2+ influx and reducing excessive neurotransmitter release
18
Q

What is an opioid by definition?

A

Endogenous or synthetic substance which has morphine-like effects and is antagonised by naloxone
- These effects are analgesia, respiratory depression, euphoria and sedation

19
Q

Opioid receptor function

A
  • GPCR 7 transmembrane proteins
  • Coupled to Gi
  • Inhibits adenylyl cylase
  • Reduces cAMP and PKA
  • K+ channels open causing hyperpolarisation and reduces neuronal excitability
  • Reduces opening of calcium voltage gated channels reducing calcium influx and reducing release of neurotransmitter
  • Found in pain regions such as PAG and thalamus as well as dorsal horn
20
Q

Dorsal horn opioid receptors

A
  • Found pre synaptically which inhibit release of substance P and glutamate
  • Found post synaptically causing hyperpolarisation of neuron
  • Activates descending inhibitory neurons as there are opioid receptors in PAG
21
Q

Pharmacological effects of opioids

A
  • Analgesia mainly by mulle
  • Given in high doses can cause respiratory depression as the neuron which detects CO2 in the brain is blocked
  • Causes constipation by reduced gastric motility
  • Causes euphoria and sedation
  • kappa causes dyspepsia
  • Causes nausea and vomiting and CTZ is packed with opioid receptors
22
Q

Tolerance of opioids

A

Meaning same repeated dose begins to have low pharmacological activity

  • Opioid binds to receptor and opens K+ channel causing hyperpolarisation causing analgesia
  • G-receptor kinase phosphorylates receptor causing desensitisation
  • Activated arrestin
  • Causes tolerance
  • Opioids do not down regulate receptors except methadone
23
Q

Synthetic opioids

A
  • Diamorphine - analgesia for tissue injury and tumour growth
  • Pethidine - Used in labour as it doesn’t reduce uterine contractions
  • Fentanyl is lipophilic so rapid onset but shorter duration than morphine
  • codeine helps with mild pain
  • Tramadol is an opioid agonist and a weak NA reuptake inhibitor
24
Q

Euphoric effects of opioids

A
  • Part of Mesolimbic pathway where neuron projects from ventral tregmental area to nucleus accumbens
  • GABA interneurons in VTA
  • Normally, GABA interneurons release GABA which bind to receptor and inhibit release of Dopamine at nucleus accumbens
  • When opioid is present it binds to receptor on GABA interneurons inhibiting release of GABA and as a result stimulates release of dopamine which causes euphoria
  • Opioid disinhibition effect
25
Mechanism of opioid dependence
- Opioid receptors get desensitised - Increases adenylyl cylase activity - Increase Na release which causes withdrawal symptoms