Sensory systems Flashcards
why do we need sensory systems?
Maintain homeostasis
Detect and react to changes in the environment
Protect the body from damaging stimuli
What receptors are involved in the sensory system of touch?
- Touch receptors
- Mechanoceptors (pressure) - activated by intense pressure on skin
- Thermoreceptors - activated by extreme temp (>45, <5°C)
-Nociceptors - pain - polymodal - activated by high intestity mechanical, chemical and thermal stimuli
What is the process of pain transmission?
Noxious stimulus
- Transduction (nociceptor endings)
- Transmission (Primary afferent fibres)
- Relay
- Integration and interpretation
- Modulation (Descending noradrenaline and serotoninergic inhibition fibres)
What are primary afferent neurons ?
A special class of neurons with their cell bodies in the dorsal root ganglia - the nociceptors
Have several markers, notably TRPV1 channels have been proposed
How does transmission of the first and second pain occur?
First - relative fast A-delta fibres mediated a sharp first pain - myelinated
Second - relatively slow C fibres mediate a delayed, longer lasting second pain - unmyelinated
What is the excitatory neurotransmitter?
Glutamate
Where do the nociceptors pathways synapse in the spinal cord?
Dorsal horn
How do nociceptive pathways project to the brain
Via spinothalamic tracts - descending inhibition and perception
How does everyone have different perceptions of pain?
- prior experiences
- attention/expectation
- Mood
- Neurochemical and structural changes
- Genetics
- Sensitisation (peripheral and central)
How can pain signals be interrupted ?
in the substantia gelitanosa of the spinal cord, which acts as a gate
What are common treatments for pain?
Analgesics
- NSAIDS
- Paracetamol
- Local anaesthetics including lidocaine
- Opioids including codeine
How do local anaesthetics block sodium channels?
- unionised LA enters the cell
- LA becomes ionised intracellularly
- LA blocks sodium channels
- Pain signals inhibited
What are the different opioid receptors?
Mu
Delta
Kappa
What are the mechanisms of the neurotransmitter release modulation in opioid receptors?
- Inhibit calcium channel function
- Neuronal hyperpolarisation via potassium channel activation
- Modulate release machinery
What is analgesia primary mediated by?
activation of Mu receptors
what was the first NSAID?
Aspirin (only one which irreversibly inhibits COX-1 through transfer of the acetyl group from aspiring to a serine residue in the COX-1 active site)
What do most NSAIDs act as?
nonselective, reversible inhibitors of the enzyme cyclooxygenase
What are COX enzymes officially known as?
Prostaglandin-endoperoxide synthase (PTGS) enzymes
What are prostaglandins?
small molecules that activate the immune system showing an initial inflammatory response
How does NSAIDs affect prostaglandins?
Blocks (inhibits) their synthesis from arachidonic acid by COX enzymes
What COX receptor does paracetamol bind to in the CNS?
COX-2
what is the chemical structure of aspirin?
One of the salicylates
what is the mechanism of action of aspirin?
- irreversibly inhibits COX-1
- this unique behaviour allows aspirin to inhibit platelet aggregation
What are examples of salicylates?
- Aspirin
- Difunisal
- Salsalate
- Choline magnesium trisalicylate
What is the chemical structure of NSAIDS?
Have propoionic acid derivatives
What are some examples of NSAIDs?
Ibuprofen
Naproxen
Ketoprofen
Flurbiprofen
What is the chemical structure of diclofenac and aceclofenac?
Has acetic acid (ethanoic acid) derivatives
What are examples of COX-2 inhibitors?
Coxibs
- celecoxib
-parecoxib
- etoricoxib
Which COX enzyme is u likely to be the reason for varying NSAID pharmacology?
COX-3
How do COX inhibitors overlay?
- structures fit in the same pocket
- hydrophobic regions tend to overlay well
- as do H-bond donors and acceptors
How do COX inhibitors overlay?
- structures fit in the same pocket
- hydrophobic regions tend to overlay well
- as do H-bond donors and acceptors
