Pain and Analgesia Flashcards
How does the brain naturally suppress perception of pain?
- descending pathways
- Periventricular nuclei (PVN) nerves in hypothalamus signals to periaqueductal grey nerves (PAG) of the mesencephalon and upper pons
- PAG nerves signal to Raphe magnus nucleus (RMN) of the pons via enkephalin release
- RMN nerves signal to inhibitory interneurons in dorsal horn of spinal cord via serotonin release
- Inhibitory neurones release enkephalin or GABA
What is the effect of GABA?
- GABA activates Cl- channels on DHN (ascending pain fibre) - Cl- moves into cell - hyperpol. - reduced DHN firing
What is the effect of enkephalin?
Activates opioid receptors expressed by A delta and C fibres and dorsal horn neurones (pre and post synaptic)
- Reduced transmission of nociception by 2 actions
PRE - inhibit opening of Ca2+ channels - reduced Ca2+ entry and less transmitter release
POST - inhibit DHN depolarisation by opening K+ channels - K+ moves out - DHN hyperpolarised
When is natural analgesia encouraged to occur?
- relaxation techniques to increase enkephalin and serotonin release centrally
- Transcutaneous electrical nerve stimulation (TENS) - stimulate peripheral inhibitory pathways by releasing enkephalins
- Application of pressure - rubbing injury - inhibitory interneurons can be activated A beta fibres (mechanoreceptors) + relaxing brain
- Heat treatments
- Ice pack
How do hot and cold treatments encourage natural analgesia?
- Heat - soothing stiff joints and lower back pain - increase BF and relax muscles
- Cold - reduce inflammation (reduce BF) and reduce nociceptor activation
What are the three way that pharmacological analgesia works?
- reduced nociceptor activation
- reduced activation of ascending DHNs
- activating descending inhibitory pathways
What are the main analgesic treatments?
Opioids, NSAIDs, local anaesthetics, anti-depressants
How do opioids work?
- Act in same way as enkephalin (inhibit Ca2+ channels pre-synaptically, open K+ channels post-synaptically, reduce signal firing)
- Stimulate RMNs to activate interneurons
What is the main problem with opioids?
Huge potential for addiction (physical and psychological dependence)
In what situations are opioids used?
Surgical pain, child birth or pain that doesn’t respond to any other drugs
What are the side effects of opioids?
- Euphoria and sense of well-being
- Constipation (opioid receptors in gut oppose parasympathetic activation of contraction)
- Nausea + vomiting (stimulation of chemoreceptors in medulla)
- Resp depression - reduction in sensitivity of respiratory centre to CO2
- Withdrawal symptoms include nausea, muscle aches, diarrhoea, trouble sleeping, low mood
How do NSAIDs reduce pain?
Inflammation - release of prostaglandins - hyperalgesia
- NSAIDs inhibit COX 1 + 2 - inhibit PG production to reduce hyperalgesia
What are the side effects of NSAIDs?
- Peptic ulcers + GI bleeding
- Na and H20 retention, hypertension, hemodynamic acute kidney injury
- Stroke, MI
How do local anaesthetics reduce pain?
Induce absence of sensation in specific part of body
- surgical and dental procedures
Block initiation and propagation of AP by pain fibres
- LA enter cell, is ionised and binds to Na+ channels closing inactivation gate - no new APs
How might bacteria effect the efficacy of LAs?
Bacteria produce acidic by-products
- more ionised LA outside cell, LA cannot enter cell via channel pore, reduced effectiveness
