pain Flashcards
How do we sense pain
Primary sensory neurons of the PNS . Soma make up a ganglion at the dorsal side of the spinal cord - Sensory neuron terminal in body tissues - synapse with spinal cord neuron which carries info to the brain. Brain interprets info as pain and sends appropriate response down descending pathway.
Are spinal cord reflexes examples of pain
No, muscular reflex not involving the brain
How could a population of DRG neurons be described
Heterogenous - diverse
How can the heterogenous population of DRG neurons be subtyped
- By size, histological difference
- The modality they respond to
Larger neurons tend to respond to non-noxious stimuli (touch - Abeta neurons are heavily myelinated)
Medium sized (A delta for immediate pain) and small sized (c neurons - unmyelinated for slow response to pain) neurons tend to respond to noxious stimuli and are involved in pain sensing (nociception)
What is the role of the receptors in nerve terminals
Gated by physical stimuli, mechanical, chemical stimuli
What type of receptor responds to changes in heat?
Trp receptors - Trpv1 responds to the component in chilli peppers giving the perception of heat.
Also channels that respond to cold - TrpM8 activated by menthol, giving mints the associated feeling of coolness.
What happens in the transduction phase
Changes stimuli into calcium release, depolarisation of the cell - activates V gated Na channels and an AP is fired/propagation and conducted along the neuron
What is sensitization
modulators released will sensitise the terminals by lowering the required threshold to trigger pain. Helps to take care of the region until the full healing process has finished
What is acute pain
Alerts the body to chemical, thermal or mechanical stimuli that has the potential to damage body tissue - has a protective role
What is chronic pain
Pain that accompanies chronic inflammatory diseases.
OR
Neuropathic pain results from damage to nerves. Nerve damage can be caused by trauma, diabetes, cancer treatment and herpetic infection
What are the 2 classes of treatment for pain relief currently
NSAIDs - inhibitors of COX enzymes which produce prostaglandins. Limitations to people with heart, renal conditions and diabetes. Side effects in the GI tract
Opioids - Receptors found in the CNS, PNS and GI. Short term side effects mental confusion, drowsiness, nausea and constipation. Tolerance and dependence become big problems
What is the problem with Opioid receptor in terms of their location
Found in the PNS, CNS and GI, optimum drug would only work in the PNS without the side effects.
Which conditions cause extreme pain
PE (Primary erythermalgia) - genetic mutation which is dominant, extremities feel and look inflamed
PEPD (Paroxysmal extreme pain disorder) - Pain when they masticate and when they defecate.
What condition causes no pain
CIP (complete insensitivity to pain) Autosomal recessive - much more likely to injure themselves significantly.
Why are voltage gated sodium channels a good target for pain relief
Essential for excitability of neurons (generation/propagation of APs) Major drug targets for local anaesthesia for cardiac arrhythmia and epilepsy
Why are inhibitors of sodium channels not used in general anesthesia
Due to spread of targets - off target detrimental effects.
What is the structure of voltage gated Na channels
One large alpha subunit - self contained ion channel and smaller beta subunits - modulate the voltage dependence of the channel and help traffick the receptor to the membrane.
How many Na VG channels do mammalian vertebrates have>
Ten cloned cDNAs - nine produced functional VG Na channels
What is the difference between the 9 Nav channels
Activation and inactivation properties differ between alpha subunits, expression pattern and level differ between alpha subunits, different neurons can fine tune their excitability
Which Nav channels are only expressed in the PNS
1.7, 1.8 and 1.9
