pain management

what effects do NSAIDs produce

• analgesic

• antipyretic

• anti-inflammatory effects

how do NSAIDs reduce pain

normally nociceptors only respond to strong or harmful stimuli.

hint: damaged cells lead to release of prostaglandins - prostaglandins lower the activation threshold of nociceptors so pain fibres fire more easily - peripheral sensitisation

they inhibit COX enzymes → reduce prostaglandin formation → reduce peripheral sensitisation and inflammation

Peripheral sensitisation - pain-sensing nerve endings (nociceptors) become more sensitive and more easily activated than normal.

how does aspirin work

irreversibily inhibits COX-1 enzymes and also inhibits COX-2 reducing thromboxane A2 synthesis and has anti-thrombotic effects

why can NSAIDs cause gastrointestinal ulceration

because prostaglandins normally protect GI mucosa

• lack of prostaglandins leads to irritation, bleeding and ulcer formation

• naproxen carries higher risk

main side effects of NSAIDs

• GI bleeding

• GI discomfort

• CNS effects (dizziness, insomnia)

• blood disorders

• fluid retention

• renal failure

what is paracetamol used for

• analgesia

• fever reduction - antipyretic

how does paracetamol work

• COX inhibition

• cannabinoid receptor activity

• activation of serotonergic descending pain pathways

• primarily acts in the brain to stop pain signals and reduce fever

why does paracetamol NOT reduce inflammation

it has little peripheral COX activity and mainly acts centrally

what are opioids

a class of drugs used to relieve pain, ranging from moderate to severe

examples of opioids

• morphine

• codeine

what are the 3 major endogenous opioids

(endogenous means opioids naturally occurring in the body)

• endorphins

• enkephalins

• dynorphins

how do opioids generally work at the synapse

they inhibit neurotransmitter release by activating inhibitory G-proteins → decrease cAMP → closing Ca2+ channels → reducing substance P

what are the 3 main opioid receptor types and how they are structured

μ (mu), δ (delta), κ (kappa); all are GPCRs with 7 transmembrane domains

why do different opioids produce different effects

they vary in receptor specificity (e.g., morphine = μ agonist; pentazocine = μ antagonist + δ/κ partial agonist)

how does receptor distribution influence opioid effects

• κ receptors → dorsal horn (spinal analgesia, dysphoria)

• μ receptors → spinal + supraspinal (euphoria, analgesia, respiratory depression)

what produces euphoric effect of opioids

activation of μ receptors in limbic system

why is respiratory depression a serious risk

μ receptor activation reduces sensitivity of brainstem respiratory centres to CO₂ — occurs even at therapeutic doses

what cause pinpoint pupils in opioid overdose

μ and κ receptor stimulation of the oculomotor nucleus → pupillary constriction

why do opioids cause constipation

they increase GI tone and decrease motility throughout tract

what symptoms occur during opioid withdrawal and why

symptoms resemble severe flu: dilated pupils, sweating, diarrhoea, nausea, insomnia — due to rebound overactivity of the nervous system after receptor downregulation

what makes neuropathic pain difficult to treat

its causes, symptoms and mechanisms are heterogenous (different) and lesions are unclear

what are the NICE first line treatments for neuropathic pain

amitriptyline, duloxetine, gabapentin, pregabalin; switch between them if not effective or not tolerated. Capsaicin for localised pain

how does pregabalin reduce neuropathic pain

binds to voltage-gated Ca2+ channels → decreases release of glutamate, norepinephrine, substance P, CGRP

how does gabapentin work

acts as NMDA antagonist and calcium channel blocker

why are TCAs (Tricyclic Antidepressants)

they inhibit serotonin and norepinephrine reuptake and block block Na⁺, Ca²⁺, K⁺ channels

• this enhances descending inhibition and reduce pain transmission

why do TCAs have so many side effects

they antagonise muscarinic receptors, H1 receptors, serotonin receptors, and alpha-1 adrenergic receptors

what is duloxetine used for and how does it work

it is a SNRI (serotonin-norepinephrine reuptake inhibitor) → boosts serotonin & norepinephrine to enhance descending pain inhibition

treats depression, anxiety and several types of chronic nerve and musculoskeletal pain

why can opioids be used in neuropathic pain but with caution

neuropathic pain sometimes responds to opioids but long term side effects limit use

what is capsaicin cream used for an how does it work

for localised neuropathic pain; activates TRPV1 receptors → depletes substance P → reduces pain signalling

what is trigeminal neuralgia

a chronic pain condition causing sudden, severe facial pain, often described as electric shocks or stabbing sensations

what is the first line treatment for trigeminal neuralgia and why

carbamazepine → stabilises inactivated sodium channels → reduces neural firing & attack frequency

why are opioids not used in neuropathic pain

Opioids are not used because it involves physical dependence - neuropathic pain is long-lasting pain so opioids are no use as they cannot be given for long time period