Pain Flashcards
What is pain?
an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
What are the two components of pain?
sensory-discriminative
affective-motivational
What is the sensory-discriminative aspect of pain?
the noxious stimulations location, intensity, and quality
What is the affective-motivational aspect of pain?
the unpleasant feeling, the fear and anxiety, and the autonomic activation that accompany expoure to a noxious stimulation
*behavioural
What are the brain areas associated with sensory components of pain?
primary somatosensory cortex
secondary somatosensory cortex
posterior insula
What are the brain areas associated with affective components of pain?
dorsal anterior cingulate cortex
anterior insula
How can hypnosis affect pain?
might alleviate pain by decreasing the activity of brain areas involved in the experience of suffering (affective)
What occurred to sensory brain areas when hypnotic suggestion was used?
the activity of the somatosensory cortext did not change with or without hypnotic suggestions
What occurred to affective brain areas when hypnotic suggestion was used?
the anterior cingulate cortex was much less active when subjects were told pain would be minimally unpleasant
What is asymbolia?
patients with lesions in the anterior cingulate or insular cortex percive noxious stimuli as painful and can distinguish sharp from dull pain and identity location and intensity aspects
but they fail to display the appropriate emotional response (not bothered or suffering from it)
Why might patients giggle in response to pain?
they can still sense the pain (danger) but the pain is no longer aversive (false alarm)
What is social pain?
the unpleasant experience that is associated with actual or potential damage to ones sense of social connection or social value (owing to social rejection, exclusion, negative evaluation, or loss)
What brainr egions are activated during soical rejection?
affective pain regions (dorsal anterior cingulate cortex and anterior insula)
as well as self reported distress was high in states of social rejection
What is the affect of tylenol on social rejection?
people taking tylenol before experiencing social rejection reported less distress than those taking a placebo
as well as less activation in affective pain regions of the brain
What is nociception?
the sensory processes of encoding and processing noxious stimuli, depends on specifically dedicated receptors and pathways distinct from the sensory processing of ordinary mechanical stimulation
What is a nociceptor?
the unspecialized free nerve cell endings that responds to stimuli that produce tissue damage or pose the threat of damage and initiates the sensation of pain
What are free nerve endings?
an axon that terminated in the skin without any specialized cell associated with it and that detects pain and/or changes in temperature
What is a receptor cell?
a specialized cell that responds to particular energy or subatnce in the internal or external environment and converts energy into a change in the electrical potential across its membrane
What are labeled lines?
the concept that each nerve input to the brain reports only a particular type off information
What is sensory transduction?
the process in which a receptor cell converts the energy in a stimulus into a chnag in the electrical potential across its membrane
What is a receptor potential?
also called generator potential
a local change in the resting potential of a receptor cell thate mediates between the impact of stimuli and the initiation of APs
What speed do pain fibers conduct at?
relatively slow speeds
due to light or no myelination on the axons
with light myelination slightly faster than without
*creates smaller diameter
What is the speed of AP a function of?
each fibers cross sectional diameter
What does the first and second pain being carried by two different primary afferent fibres create?
two differnt pain sensations
first (faster) - sharp short pain
second (slower) - dull long pain
How is noxious stimuli transduced?
into electrical acitivity at the peripheral terminals of unmyleinated C-fibre and thinly mylinated A-fibre nociceptors by specific receptors or ion cahnnels sensitive to heat, mechanical stimuli, protons, and cold
- then conducted to the spinal cord, central pathway, and cortex where pain sensation is experienced
How are TPR pathway channels opened?
Bradykinin binds to G protein coupled receptors on the surface of primary afferent neurons to activate phospholipase C, leading to the hydrolysis of PIP2 and production of IP3 -> release of Ca2+ from intracellular stores
activation of protein kinase C regulates TPR channel activity, TRPV1 channel is sensitized leading to channel opening and Ca2+ influx
What do the free nerve endings with TRPM8, TRPV1, and TPRM3 response to?
TRPM8 - temperatures below normal body temp
TRPV1 - moderate heat and capsaicin found in chili peppers
TRPM3 - high temperatures
What speed do the free nerve endings with TRPM8, TRPV1, and TPRM3 transmit at?
TRPM8 TRPV1 - along slow unmyelinated C fibres
TRPM3 - along fast large myelinated A fibres
How do the nerve cells with TRPM8, TRPV1, and TPRM3 vary with threshold?
TRPM3 - low
TRPV1 - high
TRPM8 - medium
*create a different response to stimuli
What is coding?
the rules by which APs in a sesnory system reflect a physical stimulus
What is range fractionation?
a hypothesis of stimulus intesnity perception stating that a wide range of intensity values can be encoded by a group of cells, each of which is a specialist for a particular range of stimulus intensities
What is the TRPV1 receptor?
a receptor that binds capsaicin to transmit the burning sensation from chili peppers and normally detects increases in temperature
What is the TRPM3 receptor?
a receptor found in some nerve endings that opens its channel in response to rising temperature
What is the TRPM8 receptor?
a sensory receptor found in some free nerve endings that opens an ion channel in response to a mild temperature drop or exposure to menthol
What is the affect of peripheral sensitization?
The area of mechanical hyperalgesia is larger than the flare
the mechanical threshold for pain is significantly decreased post injury
What are potential mediatiors fo peripheral sensitizaition?
Mast cells releasing mediators (histamine, bradykinin)
macrophages releasing cytokines (bradykinin)
What is the effect of the mediators on peripheral sesitization?
may act direcly to alter the sensitvity of peripheral nociceptors or indirectly via coupling to one or more peripheral membrane bound receptors
binding lignads to receptors can initial a cascade of events that includes activation of second messenger systems and alteration of gene regulation
Explain the mechanism of peripheral sensitization
with inflammation, components of the inflammatory soup (bradykinin or prostoglandins) bind to G protein coupled receptors and indue activation of protein kinases A and C in nociceptor peripheral terminals, which then phoshorylate ion channels and receptors
results in the threshold of activation of the transducer receptor is reduced, and the excitability of peripheral terminal membrane increases, producing a state of heightened sensitivity
What is allodynia?
pain caused by a normally non-painful stimulus
What is hyperalgesia?
a heightened experience of pain caused by a noxious stimulus
What is hypoalgesia?
a decreased perception of pain caused by a noxious stimulus
What are the efferent actions of nociceptors?
a noxious stimuli will also lead to an AP that propagates efferently to peripheral branches
they lead to release neuropeptides that can stimulated epidermal and immune cells, or lead to vasodilation, plasma extravasation, and smooth muscle contraction
What is the role of CGRP in neurogenic inflammation?
produces dilation of peripheral blood vessels
resultant edema causes additional liberation of bradykinin
What is the role of substance P in neurogenic inflammation?
acts on mast cells to evoke degranulation and the release of histamine which direclty excites neurotransmitters
it alos produced plasma extravasation
What are the four stages in neurotrophins as pain mediators?
- peripheral exposure to NGF - binds to primary nociceptive terminals
- retrograde transpot of signalling endosomes - increase excitability
- increased transcription of BDNF - enhanced expression of BDNF
- central reslease of BDNF - released from sensoru terminals and spinal cord
What is the role of pain specifc sodium channels?
NaV1.7 channel
transform generator potentials from the pain signaling pathway into AP in the adjacent pacemaker zone
transmitted slong the afferent sensory fibers
Explain how a grasshopper mouse does not feel pain from the bark scorpion venom
The bark scorpion toxin activates Na1.7 channels in grasshopper and lab mice
in grasshopper mice the toxin protently inhibits the NaV1.8 channel in the same sensory neurons tipping the balance to inhibit AP firing in nociceptors
What fibers do neurons in lamina I of the dorsal horn receive input from?
direct - myelinated A nociceptor fibers
direct & indirect - unmylinated C nociceptor fibres via interneurons on lamina II
What fibers do neurons in lamina V of the dorsal horn receive input from?
low threshold input from large diameter myelinated fibers A of mechanoreceptors
from nociceptive afferent fibers A and C
Where does lamina V neurons send dentrites to?
lamina IV where they are contacted by the terminals of AB primary afferents
Where do dendrites in lamina III go to?
arising from cells in lamina V are contacted by the axon terminals of lamina II interneurons
What is the neural basis of referred pain?
convergence of visceral and somatic afferent fibers
nociceptive afferent fibers from the viscera and fibers from specific areas of the skin converge on the same projection neurons in the dorsal horn. The brain has no way of knowing the actual site of the noxious stimulus and mistakenly associates a signal from a visceral organ with an area of skin
What are the two classes of synapitc vessesl on the terminal of a C fibre on a dendrite and what do they contain?
small electron-lucent vesicles contain glutamate
large dense-cored vesicles hold neuropeptides
Where are glutamade and the peptide substance P scattered?
in the axoplasm of a sensory terminal in lamina II of the dorsal horn
Where is substance P in the highest concentration?
in lamina I
How does pain ascend the spinothalamic system to reach the brain?
sensation of pain travels from its origin to the brain via the spinothalamic system crossing the midline in the spinal cord before ascending to the thalamus
What is the anterolateral system (spinothalamic system)?
a somatosensory system that carries most of the pain and temperature information from the body to the brain
What is the anterolateral pathway (spinothalamic)?
primary afferent axons terminate in dorsal horn -> SECONDARY AXONS CROSS MIDLINE -> ascend contralateral anteriolatereal column to thalamus
*pain and temperature
What is the dorsal column pathway?
primary afferent axons enter spinal cord -> ascend the ipsilateral dorsal columns -> synapse in medulla -> SECONDARY AXONS CROSS MIDLINE -> ascend to contralateral thalams
*mechanosensory
What is a hemicord lesion (brown-sequard syndrome)?
a lesion restricted to the left half of the spinal cord results in dissociated sensory loss and mechanosensory deficits on the left half of the body, wiht pain and temperature defecits on the right
What are the descending pathways?
sertonergic pathway
noradrenergic system
What is the function of the descending pathways in the spinal cord?
inhibit nociceptive projection neurons through direct connections as well as through interneurson in the superficial layers of the dorsal horn
both pathways recive input from neruons in the periaquaductal grey region
What do local enkephalin containing interneurons exert?
both pre and post synapic inhibitory actions at synapses
What do serotonergic and noradernergic neurons in the brainstem activate and suppress?
activate the local interneurons and suppress the activity of the spinothalamic projection neurons
What is naloxone?
a potent antagonist of opiates that is often administered to people who ahve taken drug overdoses
it blocks receptors for endogenous opiods
What is analgesia?
absence of or reduction in pain
What are opiates?
a class of compound that exert an effect like that of opium, including reduced pain sensitivity
What are endorphins, enkephalins, and dynorphins?
three kinfs of endogenous opioids, substances that reduce pain perception
What are endogenous opioids?
a class of peptides produced in various regions of the brain that bind to opiod receptors and act like opiates
What is an opioid receptor?
a receptor that responds to endogenous and/or exogenous opioids
What is periaquaductal gray?
the neuronal body - rich region of the midbrain surrounding the cerebral aqueduct that connects the third and fourth ventricles
involved in pain perception
What are the two ways of regulation of nociceptor dingals at dorsal synapse?
- activation of nociceptor leads to the release of glutamate and neuropeptides from the primary sensory motor neuron, producing an excitatory postsynapic potential in the projection neuron
- opiates decrease the duraction of the postsynaptic potential, probably by reducing Ca2+ influx and thus decreasing the release of transmitter from the primary sensory teminals
- opiates hyperpolarize the dorsal horn neurons by activating a K+ conductance and this decrease the amplitude of the postsynaptic potential in the dorsal horn neuron
Where are the opioid receptors in the body?
brain
brainstem
spinal cord
peripheral neurons
intestine
What are peripherally restricted opioids?
molecules that don’t cross the blood brain barrier
How does a new opiod target disease specific conformations?
by selectively activating opiod receptors where acific conditions prevail (tissues affected by inflammation or injury)
*does not affect health tissue
What is the placebo effect?
a physiological response following the administration of a pharmacologically inert “remedy”
- external and internal environment
