Pain Flashcards
Pain is accompanied by:
Erythema
Oedema
Hyperalgesia
(redness of the skin)
(swelling of the skin due to excess extracellular water)
(hypersensitivity of surrounding area)
Example: cut skin
activates the…
which activates the…
the fibers terminate in the…
Bundles of fibers going from the spinal cord to the…
The area that the fibers reach in the CNS is the….
Central grey – a descending pathway, from the brain to the…
From the central grey info goes to the spinal cord to…
Two types of sensory fibers go to the…
There is two different pathways that go from the spinal cord to the….
Reflects the two different types of…
One pathway is related to…
Other pathway is related to…
nociceptors sensory fibers in the skin spinal cord CNS thalamus (relay station for sensory info)
important structure in the hindbrain spinal cord (inhibitory system) temper the pain info (inhibit the pain)
spinal cord
thalamus, and two different pathways from the thalamus to the cortex
pain experienced.
acute/sharp pain
dull/diffused pain (difficult to localize)
Nociception
Heat stimulus over finger, record the outgoing info from the sensory fibers.
At low temperatures thermoreceptors become active, which…
At 43 degrees and above, the fibers are maximally active (painful heat applied)…
mediate first sensory response to warmth.
another group of fibers (nociceptors) start to fire.
Pain is mediated via…
Pain fibers do not have specialized receptors, but have…
free-ending nerves.
free nerve endings.
Transient Receptor Potential (TRP) ion channel family:
4 examples…
Located on…
TRPs More than... Great... Activated by... TRPV1 (?), TRPA1 (?)... TRPV1 activated by... - Agonist at... - PAM at... TRPA1 activated by...
menthol, capsaicin, thiosulfonates, isothiocyanate
the sensory fibers.
30 different ones diversity GPCRs heat, cold H+ pH < 6 pH 6.5- 7.0 oxidative stress
Nociception – the relationship between B2 and TRPV1
Bradykinin (neuropeptide) is released from damaged cells –selectively influences pain fibers, through B1 (chronic pain) and B2 receptors (acute pain)
Bradykinin binds to B2 receptor (metabotropic receptor)
DAG phosphorylates the TRPV1 receptor keeping it sensitive > prolonged activation of the TRPV1 channel.
Tissue damage opens TRPV1 channel via production of H+, activates B2 receptor by production of bradykinin and bradykinin b2 receptor through PLC/PKC phosphorylates the TRPV1, keeping the channel open for longer, synthesis the channel.
B2 receptor activation keeps TRPV1 sensitive
DAG activated PKC which phosphorylates TRPV1
Bradykinin phosphorylates TRPV1 enhancing its function
Bradykinin activates arachidonic acid/prostaglandins
Prostaglandines further phosphorylate (sensitize) TRPV1
TRPs: TRPV1 related to... Activated by... Involved in... TRPA1: related to... Activated by... Involved in...
heat/nociception
capsaicin, H+, ATP
arthritis, migraine, cancer pain, irritable bowel syndrome
cold/nociception
wasabi, oxidative stress products
arthritis, diabetes, colitis, pancreatitis
Fibers that send nociceptive information to the brain are the smallest peripheral fibers…
Pain is mediated via…
The diameter of the axons is directly related to the…
C- fibers are the….
delta fibers and c-fibers
delta fibers and c-fibers
speed with which action potentials travel across the axons.
smallest, slowest and un-myelinated
First pain > delta fibres (increase in pain sensitivity) > short period of pain
Overtime
Second pain > c fibres (decrease in pain sensitivity) > longer period of pain
Activate delta fibers with a…
Rapid increase in pain sensitivity, mediated by…
noxious stimulus
the delta fibers
Two kinds of pain:
(1) Sharp pain
(2) Dull pain
Fast, Well localized, Non emotional, Through fast Aδ fibers
Neospinothalamic pathway
Slow, Diffuse, Strong emotional, Through slow C fibers
Paleospinothalamic
The neospinothalamic pathway (sharp pain) terminates in the somatosensory cortex
The Aδ fibers terminate in the…
and from there, via the neospinothalamic pathway..
The C-fibers terminate in deeper layers of the…
Via the paleospinothalamic pathway, information is…
superficial layers of the spinal cord
innervate specific thalamic nuclei and terminate in the somatosensory cortex.
spinal cord.
transferred to other parts of the thalamus and ultimately to limbic structures such as the anterior cingulate cortex.
The descending pain pathway
Descending pathway can regulate the…
Central gray area in the midbrain involved in the…
intensity of the pain
descending pathway
The descending pathway activates enkephalin interneurons in the spinal cord that reduce…
Descending pathway activated – serotonin is released, activates the…
Enkephalin is released, inhibits the release of…
the release of SP
enkephalin interneurons
SP, as a result, less info from the skin damage is passed onto the spinothalamic cells, therefore less info goes into the CNS.
Non-Narcotic Analgesics:
Examples…
aspirin, ibuprofen and paracetamol (NSAIDs)
Non narcotic analgesics block…
There are two (three) forms of cox
Traditional NSAIDs block…
cox2 involved in the…
Side effects:
Kidney failure…
Stomach ulcers and bleeding…
Newer NSAIDs more selective for…
Paracetamol: acts via... no effect... can lead to... does not... may directly interact with...
cyclo-oxegenase (cox)
(cox1 and cox2)
both forms of cox
regulation of pain
(cox1 inhibition in the kidney)
(cox1 inhibition in the stomach)
Cox1 is located in the kidney and the stomach, which explains why most NSAIDs can lead to kidney failure and stomach ulcers.
cox2 (less side effects)
different mechanisms on the stomach or the kidney. liver toxicity, which limits its use. ....inhibit cox activity (tough it does reduce cox in the brain). TRPs
