Lecture 7- Pain analgesia Flashcards
Describe the descending pathway of natural analgesia
Periventricular nuclei (hypothalamus) > signal to periaqueductal gray of mesencephalon/ upper pons PAG nerves signal to Raphe magnus nucleus of pons via enkephalin release> RMN nerves signal to inhibitory interneurons in dorsal horn of SC via serotonin release
What effect does enkephalin have on descending pathways?
Enkephalin activates opioid receptors expressed by Ad and C fibres/DHN
Reduced transmission of nociception by 2 actions
Also inhibit DHN depolarisation by opening K+ channels, causing K+ to move out and DHN hyperpolarisation
Also act presynaptically inhibiting Ca2+ channels opening- less transmitter release
What techniques are used in natural analgesia?
Application of pressure? Transcutaneous Electrical Nerve Stimulation- stimulating peripheral inhibitory pathways by releasing enkephalins
Rubbing- inhibitory interneuron activation by AB fibres (mechanosensors)
Hot and cold activation of analgesia
Heat treatments- soothing stiff joints/lower back pain, increasing blood flow and relaxing muscles
Cold- reduce inflammation (reduced BF) and nociceptor activation
(nociceptors/ AB nerves may also be thermosensors)
Opioids- mode of action
Same ways as enkephalin- reduce nociceptor activation
Also inhibit DHN depolarisation by opening K+ channels, causing K+ to move out and DHN hyperpolarisation
Also act presynaptically inhibiting Ca2+ channels opening- less transmitter release
Side effects of opioids
Dependence- physical/psychological
Euphoria/ sense of wellbeing, helpful in terminal pain
Constipation- O.Rs in gut oppose PS activation of contractions
Nausea/vomiting- stimulation of chemoreceptors in medulla
Resp. depression- reduction in sensitivity to CO2 of Resp. centre
Withdrawal symptoms from opioids
Nausea Muscle aches diarrhoea trouble sleeping low mood
NSAIDS- mode of action
Inflammation- increased prostaglandins > hyperalgesia (central/peripheral sensitisation of nociceptor)
NSAIDs inhibit COX (COX-1/2) E.g aspirin/ ibuprofen
Inhibit PG production- lessen hyperalgesia
Different types of NSAIDS and their type of pain inhibition
Non-selective- diclofenac, ibuprofen, naproxen (Peripheral inhibition of pain)
COX-1 selective- low dose aspirin (Peripheral inhibition of pain)
COX-2 selective- Celecoxib, rofecoxib (peripheral inhbition of pain)
COX-3 selective- Paracetamol- central inhibition of pain
Side effects of COX inhibition in different systems
GI- COX-1 inhibition can cause peptic ulcers/ GI bleeding
Kidney- COX inhibition can cause Na/H2o retention, hypertension, hemodynamic acute kidney injury
COX-2> COX-1 inhibition- Stroke, MI
Low dose aspirin irreversibly inhibits platelet COX-1
Local anaesthetics
Block inititation and propagation of action potential by pain fibres
LA enters cell, ionised and binds to Na+ channels closing inactivation gate: no new AP’s can be transmitted
If LA already ionised its entry restricted to via pore of channel
How might bacteria, that produce acidic byproducts, affect LA efficacy?
More ionised LA outside, block reliant on LA entering cell via channel pore
Reduced effectiveness
Why might LAs be given in conjuction with VCs, eg adrenaline?
Confine spread to other tissues and reduce blood loss
Side effects of local anaesthetics
Common- nausea, dizziness, bruising, redness, itching/swelling at injection site
Less common- drowsiness, mental/mood changes, ringing in ears, vision changes, tremors, numbness, head/backache
Na+ channels are throughout body and so LA can spread
Lidocaine
Antidepressants as analgesics
Increase serotonin levels in synaptic cleft- increases activation of descending analgesic pathways, leading to dereased nociceptive signals to DHN
Also helps break cycle of pscyhological/physical effects of pain
Helpful in management of chroinc/neuropathic pain
