Pharmacology of Pain Flashcards
describe the different time factors and what leads to pain
- Seconds to minutes – activation of nociceptive specific/wide dynamic range neurones proportional to the intestiny of the stimulus (hyperacute phase of pain)
- Minutes to days – sensitisation of terminals at the injury site and delayed central (e.g. spinal level) sensitisation
- Days to months – changes in the supply of trophic factors, sprouting of fibres and abnormal innervation, trans-synaptic degeneration, nervous system changes structurally according to the pain, the pain is underlined by the structural changes as well
what are the different types of pain
- Nociceptive (acute noxious mechanical, thermal, electrical stimuli)
- Inflammatory (semi-acute or chronic ischaemia, infection)
- Neuropathic (e.g. chronic maladaptive plasticity after traumatic injury)
what areas of the brain are key in pain modulation
- periaquaductal grey and raphe nuclei are key in painmodulaiton
Describe the dorsal horn local circuits which can lead to pain
- there are may targets at the spinal level at the first synapse with second order neurones
- c and A dela fibres release neurotransmitters
What are the pharmacological targets for the dorsal horn local pain circuits
Targets: COX-2, nitric oxide synthase (NOS), glutamate receptors (NMDA and non-NMDA), neurokinin1 (NK1) receptors, opioid receptors.
what pathway carries pain and temperature
Pain and temperature is carried in the anterolateral spinothalamic pathway
describe the pathway of the anterolateral spinothalamic pathway
Primary afferent makes a synaptic connection at segmental level.
There is then crossover by the second order neurones which project to the thalamus then to the somatosensory cortex.
stimulation of certain brain sites ….
inhibit pain
what brain sites inhibit pain
The most effective sites are PAG (periaqueductal gray) and the nucleus raphe magnus (NRM)
How does PAG and the nucleus raphe Magnus inhibit pain
Electrical stimulation of PAG or NRM inhibits spinal thalamic cells, (i.e. spinal neurons that project monosynaptically to the thalamus) in laminae I, II and V so that the noxious information from the nociceptors are modulated at the spinal cord level
Electrical stimulation of the PAG elicits release of endorphin while stimulation of the NRM causes release of serotonin (5-HT).
What can be produced in certain stressful situations
Analgesia
- This phenomenon is called stress induced analgesia (SIA). For example, soldiers wounded in battle or athletes injured in sports events sometimes report that they do not feel pain during the battle or game; however, they will experience the pain later after the battle or game has ended
What causes stress induced analgesia
- endogenous opacités are released in response to stress and therefore inhibit pain by activating the midbrain descending system
what are factors that influence pain perception
- Cognition – attention, distraction, control, hypervigilance, catastrophizing, re-appraisal
- Context – beliefs, expectations, placebo
- Genetics
- Injury – peripheral and central sensitization
- Mood – depression, anxiety, catastrophizing
- Chemical and structure – atrophy and opiodermergic/dopaminergic dysfunction
what are the three main classes of opioid receptors
Mu (μ1, μ2, μ3)
Delta (δ1, δ2)
Kappa (κ1, κ2, κ3)
where are the opioid receptors in the brain
- all three are widely distributed
What does the wide spread of opioid receptors in the brain explain
The widespread distribution of opioid receptors explains the broad spectrum of effects induced by opioid agonists.
What are the 3 major classes of endogenous opioid peptides that interact with the opaite receptors in the CNS
Proopriomelanocortin (POMC) - derived
Proenkephalin - derived
Prodynophin - derived
name a pro-nociceptive endogenous system
CCK
What type of receptors are opioid receptors
G protein receptors
How does morphine work
- binds to the G protein opioid receptors
- couples with GI
- this inhibits the production of cAMP
Does this by… - Activation of potassium conductance into cell, therefore decreasing excitability and hyper polarising the membrane
- Decreases calcium conductance into cell through calcium channels. This suppresses synaptic transmission by decreasing release of NTs.
what does methadone do
helps heroin addiction by allieviating symptoms of withdrawal, without giving the high.
what are the effects of the main opioid receptors
Central nervous system = Analgesia, respiratory depression, drowsiness/lethargy, euphoria/dysphoria, miosis, emesis.
Cardiovascular system = hypotension
GI = delayed gastric emptying, decreased biliary and pancreatic secretions, urinary urgency, itching
what is an opiate antagonist
- Naloxone is an opiate antagonist with a short half life
= short half life is important as you have to continuous infuse it every 20 minutes or so in order to reverse the effects of the opiate completely
What is the risk of tolerance and addition to opioids
- morphine requires careful dosing
- do not under dose morphine due to fear of tolerance
- dosage should be controlled by the patient
- effective analgesic dose varies from patient to patient as there is difference int he MU receptor opioid gene
- can switch opioids if they become tolerant to a particular drug
