Flashcards in Nociception Deck (56):
The first synapse for vibratory neurons is ___________.
the caudal medulla
The first synapse for pain neurons is ____________.
the posteromarginal nucleus in the dorsal horn of the spinal cord
For the warm/cold receptors that are not painful, which are myelinated?
Alpha-delta (cool): lightly myelinated
C (warm): unmyelinated
Warm receptors increase their firing rate in response to ____________.
increases in temperature
Cool receptors increase their firing rate in response to ______________.
decreases in temperature
There are 10x as many __________ receptors as ________ receptors.
What is nociception?
Sense of pain
What molecule does the P2X receptor sense?
ATP – this is important because it acts as a sensor of cytolysis
Differentiate activators and sensitizers.
Activators bring a neuron to threshold and sensitizers make it easier for a neuron to get to threshold.
Some activators and sensitizers include _____________.
Activators: bradykinin, 5HT
Sensitizers: substance P, prostaglandins
Describe the triple response.
After an injury, you get (1) a red center and (2) an edematous wheal (from bradykinin released from tissue damage) as well as (3) a flare of pinkness around the edema due to C fibers releasing substance P.
Bradykinin is a _____________.
vasodilator and inducer of vascular permeability
What are flares around wounds?
Pink areas that radiate outward
What are the qualitative differences between first pain and second pain?
First: tolerable, well-localized
Second: horrible, not well-localized, aching/throbbing
__________ and __________ are products of sensitization.
Hyperalgesia and allodynia
NMDA receptors can functionally become AMPA receptors by __________.
phosphorylation (which is accomplished by neurokinase I)
What causes hyperalgesia after a surgery?
Phosphorylation of the NMDA receptors
What neurotransmitter activates the inhibitory interneuron?
Activation of inhibitory interneurons does what to the pre- and postsynaptic neurons?
Pre: blocks calcium channels (which thence makes the neuron release fewer vesicles!)
Post: opens potassium channels, which hyperpolarizes the membrane (making the neuron require more vesicle to become activated)
Stimulation of the ____________ leads to widespread analgesia.
Enkephalin is an ______________.
What is tabes dorsalis?
A condition of dorsal column degeneration (that is, degeneration of A-beta axons)
TENS stands for ___________.
transcutaneous electrical nerve stimulation
The main mechanism of systemic opiates is _______________.
activation of the periacqueductal gray area – there are "lots of" opiate receptors in the PAG – leading to widespread analgesia
What is the principle of giving opiates in the spine (either epidural or intrathecal [which is subarachnoid])?
The inhibitory interneurons are in the spine; thus, giving opiates here leads to activation of the inhibitory neurons while avoiding the systemic side effects.
The cannabinoid receptors have been shown to interact with two systems: ________________.
1) opiate system
2) immune system:
- decreasing proinflammatory cytokines
- increasing anti-inflammatory cytokines
Fascinatingly, the placebo effect has been shown to be blocked by _____________.
naloxone; this is taken as evidence that the placebo effect relies on endogenous opiates (i.e., the frontal cortex – most likely – has a connection to the periacqueductal gray matter)
Define neuropathic pain.
(n.) a state in which one experiences debilitating pain in the absence of external stimuli
There are two rare disorders that lead to extreme pain states. What are they and what causes the disorder?
Primary erythralgia (PE) and paroxysmal extreme pain disorder (PEPD)
Both are due to gain-of-function mutations in sodium channels, making them hyperactive.
True or false: a child who bites their lips or tongue to the point of mutilation likely has a condition caused by a gain-of-function mutation.
This is a classic sign of CID (congenital ionchannelopathy disorder) – a syndrome in which a loss-of-function mutation in pain-sensing sodium channels leads to decreased ability to sense pain.
What temperature ranges are encompassed by "cool" and "warm" receptors?
Cool: 10 - 37
Warm: 30 - 48
While warm and cool receptors are best at detecting changes in temperature, they can also ____________.
detect absolute temperature (with cool receptors firing more frequently at lower temperatures)
Cool receptors are found on ________ fibers, while warm receptors are found on _______ fibers.
We've previously learned that the spinothalamic tract synapses on the VPL in the thalamus. To what other sites does the anterolateral system synapse?
The reticular formation (which thence goes to the hypothalamus) in the brainstem and the mesencephalon (aka midbrain, aka periacqueductal gray matter)
The cingulate gyrus also activates in response to painful stimuli and is thought to play a role in the _________ response to pain.
emotional (because the cingulate gyrus is part of the limbic system)
Where do painful sensations in the face/head synapse?
In the spinal trigeminal nucleus
On which axons do hot (greater than 43 degrees C) stimuli travel?
A-delta (think of Dairy queen: Cool treats, Hot eats)
Noxiously cold stimuli travel on ________ fibers.
Intense pressure stimuli travel on _________ fibers.
What kind of fibers are polymodal fibers? What information do they transduce?
C fibers; mechanical and chemical pain (chemical pain includes moieties like capsaicin and acid)
VR-1 is activated by ______________.
heat and capsaicin
True or false: C fibers conduct faster than A-delta.
False (A-delta are myelinated and conduct faster)
What is the fiber basis of the first-localized-then-diffuse pain?
A-delta are finely localized and arrive first, then C fibers – which are diffusely spread – arrive later
The first fibers to be blocked by anoxia are _____________.
the more metabolically active A-beta and A-delta
Bradykinin is produced by cleavage of ___________.
What is the cellular basis of referred pain?
Visceral-organ-pain neurons synapse on the same dorsal-horn neurons as external pain, and thus internal pain manifests as diffuse, C-fiber-like pain from a limb or external feature.
The primary neurotransmitter used at the first synapse (in the dorsal horn) is __________, which activates these channels:
glutamate; AMPA and NMDA
What is the receptor mechanism of substance P?
It binds to the neurokinin 1 receptor and causes potassium channels to close, thus depolarizing the cell. This allows glutamate to activate NMDA channels.
Why does CNS substance P lead to long-term sensitization?
Because it is not efficiently removed from the extracellular environment
Inhibitory interneurons stem from ______ fibers.
What is the pathophysiology of tabes dorsalis?
Advanced syphilis leads to the destruction of A-beta fibers and consequent hyperalgesia
True or false: stimulation of top-down analgesia leads to action potentials in the nucleus raphe magnus in the medulla.
True! This is the pathway of the periacqueductal gray matter
Neurons from the nucleus raphe magnus are activated by ___________ and synapse on __________ that use enkephalin.
serotonin; inhibitory interneurons
Why are opiates sometimes given intrathecally?
Because they block transmission of pain signals in the spinal cord without systemic effects
What is the dominant theory behind the stress-induced analgesia phenomenon?
That the limbic system (cingulate gyrus) stimulates the PAG