Nociceptive Pain

PH3113 Unit 3

What fibres are involved in nociception?

A delta fibres and C fibres

What type of pain do A delta fibres transmit?

Sharp, fast pain that triggers protective reflexes

What type of pain do C fibres transmit?

Slow throbbing pain that promotes rest and healing

What are the three stages of pain processing?

Nociception

Pain gating

Pain perception

Where does pain gating occur?

Dorsal horn of spinal cord

What is pain perception?

Conscious awareness of pain in the brain

What brain regions are involved in pain perception?

Thalamus, limbic system, cortex

What are the roles of prostaglandins in pain?

Sensitise nociceptors and decrease the firing threshold

Do prostaglandins directly cause pain?

No

Which chemicals stimulate nociceptors?

Bradykinin, histamine and serotonin

What metabolite of paracetamol blocks sodium channels?

AM404

What do opioids do at spinal cord level?

reduce transmission of nociceptive signals

Which opioid receptors are involved in pain modulation?

Mu, delta and kappa receptors

Which opioid receptor is most clinically important?

Mu

Which opioids target Mu receptors?

Morphine, fentanyl, heroin and codeine

What are the effects of Mu receptor activation?

Analgesia, euphoria, respiratory depression, constipation, miosis and dependence

Which opioid receptor is associated with dysphoria and sedation?

Kappa

What type of receptors are opioid receptors?

GPCRs

How do opioid receptors reduce pain transmission?

reducing neurotransmitter release and hyperpolarising neurones

What is the most dangerous side effect of opioids?

respiratory depression

Give examples of full Mu agonists.

morphine, codeine, diamorphine, pethidine, methadone

Give examples of partial mu agonists

Buprenorphine, pentazocine, meptazinol

What are the advantages of partial agonists?

Lower respiratory depression

Give examples of opioid antagonists

Naloxone and Naltrexone

What are the two major metabolites of morphine? Which is analgesically active and which contributes to neurotoxicity?

M3G (neurotoxicity) and M6G (analgesic)

What enzyme converts codeine to morphine?

CYP2D6

Why is heroin more potent than morphine?

lipophilic and crosses the BB rapidly

Tramadol, as an opioid, what additional mechanism does it have?

serotonin and noradrenaline reuptake inhibition

Why must opioids be used cautiously in head injury?

Can mask neurological symptoms

What symptoms occur with opioid withdrawal?

Anxiety, restlessness and hypervigilance

What is opioid hyperalgesia?

Increased pain sensitivity caused by opioid therapy

What is allodynia?

Non painful stimuli being perceived as painful