Pain/temp Flashcards
thermoneutral point
33 degrees C; similar firing rates of warm/cool receptors
temp range for cool receptors
10-37C
temp range for warm receptors
30-48C
temperature range for sensing skin temperature
10-48 C
2 classes of temp receptors
cool and warm receptors
Are there more cool receptors or warm receptors
Cool receptors; about 10x as many warm receptors
where are cell bodies of temperature receptors
DRG or trigeminal if in face
where are temp receptors located
in the skin on free nerve endings
What type of fibers are cool receptors associated with
Aδ
What type of fibers are warm receptors usually associated with
C fibers
where is first temperature synapse
in dorsal horn of spinal cord and the spinal trigeminal nucleus (for limbs/body, head/neck, respectively)
First order neurons
in periphery and synapse on second order neurons in dorsal horn of spinal cord
Where are the second order neurons going
Thalamus then to sensory cortex via spinothalamic tract; another tract – spinoreticular tract conveys info via reticular formation to hypothalamus (this info important for control of body temperature – an autonomic function)
spinoreticular tract
plays role in emotional response to pain
Tracts of anterolateral system
spinothalamic, spinoreticular, spinomesencephalic
Spinothalamic tract
conveys pain to thalamus.
- Projects to nuclei of ventrobasal thalamus (includes VPL, VPM)
- process info related to localization of pain/project to somatosensory cortex
spinoreticular tract
conveys pain inputs leading to forebrain arousal/elicits emotional and behavioral responses via connections to emotional circuits of brain
- terminates in medulla/poins
Spinomesencephalic tract
projects to midbrain periaqueductal gray region
- important for descending control of pain
other cortical regions activated in pain processing
cingulate gyrus: part of limbic system and contributes to emotional component of pain sensation
insular cortex: processes info related to autonomic component of pain
Where do axons from trigeminal nucleus enter
at level of pons– descend to caudal position before forming first synapse
site of first synapse of trigeminal ganglion axons
spinal trigeminal nucleus (in region from rostral spinal cord to caudal brain stem)
spinal trigeminal nucleus
receives inputs from head/neck via trigemina ganglion neurons
importance of pain
warn of probable injury; help avoid or minimize tissue damage
Thermal pain receptors
Thermal nociceptors; activated by extreme temperatures (43C)
fibers associated with nociceptors activated by extreme heat
Aδ
fibers associated with nociceptors activated by extreme cold
C
receptors for Intense pressure
mechanical nociceptors– associated with A (delta) fibers
Receptors activated by high-intensity mechanical, chemical or thermal stimuli
polymodal nociceptors
fibers associated with polynodal nociceptors
C fibers
Vanilloid receptor
VR
- VR-1 = capsaicin receptor
- strongly activated by capsaicin and weakly by acids; also activated by moderate heat (43C)
- expressed on polynodal nociceptors
- receptor part of ion channel complex
- receptor activated–> non-selective cation channel opens –> depolarization
Other nociceptors
- ion channels gated by ATP/acids
- ATP opens ionotropic P2X receptors
- Acid-sensing channels = ASICs (4 different ASIC genes expressed on C fiber nociceptors)
different kinds of pain
nocioceptive, inflammatory, neuropathic
Are A (delta) receptors myelinated
poor myelination but better than C
Path of 3 anterlateral system
Spinothalamic –> thaamus –> somatosensory cortex
Spinoreticular –> reticular formation –> hypothalamus & various thalamic nuclei(behavior/emotion)
Spinomesencephalic –> midbrain –> mesencephaon (descending modulatio of pain)
Anterolateral system sensations
pain/temperature
Anterolateral system primary sensory neuron
DRG(Aδ, C fibers)
Primary synapse of anterolateral system
Dorsal horn (spinal cord)
decussation location of anterolateral system
in spinal cord at same level of synapse in dorsal horn
Input vs ascending information of anterolateral system
contralateral
DCML sensations
touch/proprioception
Primary sensory neuron of DCML
DRG (trigeminal) - A beta
1st synapse of DCML
Nucleus fasiculus gracilis or cuneatus in medulla
Decussation location of DCML pathway
medulla
Input vs ascending information of DCML pathway
Ipsilateral to contralateral
when do cool receptors increase firing rate
when temperature decreases
when do warm receptors increase firing rate
when temperature increases
transient response
tells us about change in temperature per time
Sustained response
absolute temperature
Molecular receptor types
ASIC (acid), P2X (inflammation, purigenic receptor–ATP), VR-1 (capsaicin-chemical, temp)
type of fibers for pain
Aδ and C
hyperalgesia
increased sensitivity to pain
allodynia
nonnoxious stimulus now painful
Aδ vs C fibers
- both small diameter but C smallest
- Aδlightly myelinated vs C not
- both conduct more slowly than A-alpha and beta; Aδ more rapid than C so that information gets to CNS before info from C fibers
- receptive field associated with Aδ fibers slightly smaller, so Aδ fibers better localized – better spatial discrimination
pain sensed by Aδ fibers
first pain–localized tolerable pricking pain
Second pain
sensed by C fibers– burning, intolerbable, diffusely localized, “burning” pain
If pressure applied, in what order will you lose sensation
- those in high metabolic demand most vulnerable
- larger diameter will become nonconductive first
- lose Aalpha and Abeta (touch/vibration/joint position/joint movement; paralyzed)–>Aδ (prickling pain) –> C (burning pain)
Give electrical stimulation, which fibers activated first
Aalpha and Abeta (touch/vibration/joint position/joint movement)–>Aδ (prickling pain) –> C (burning pain)
give anesthetic, what is suppressed
C (burning pain)–>Aδ (prickling pain) –> block motor axons/touch afferents (paralysis)
what is released by damaged cells
K, ATP, Prostaglandins, acid
- mast cels recruited to tissue damage and release serotonin/other chemicals
What compounds are considered activators of nociceptors
Bradykinin, acid (H), K, 5HT
- Bradykinin from cleavage from inactive kininogen
Sensitizers
depolarize neuron a little but not to get full AP; makes it easier for next stimulus to reach AP
Examples of Sensitizers
- Prostaglandins, Substance P
- ATP, ACh, 5HT (single or together)
Primary hyperalgesia
sensitization of nociceptors (since it occurs in first site of pathway)
Triple response
as a result of injury – characterized by: reddening, wheal and flare
In triple response, what is responsible for the redness, edema/ wheal, and flare
Flare (pink)- Substance P
Redness and Wheal (edema) - Bradykinin
intrathecal
within subarachnoid or subdural space
Rexed’s lamina II
area in substantial gelatinosa of dorsal horn where C fibers terminate
Nociceptive afferents synapse
dorsal horn of spinal cord (limbs/trunk) or trigeminal spinal nucleus (head/neck)
Modality segregation
afferents comveying info of different sensory modalities reach CNS in organized manner and segregate to different regions of dorsal horn (laminae)
- Adelta fibers terminate in different laminae
referred pain
due to convergence of visceral and somatic pain inputs; some pain -activated dorsal horn neurons get input from both visceral and cutaneous afferents
- few dorsal horn neurons solely devoted to visceral pain processing
- Cells contacted by dorsal horn neuron won’t be able to distinguish between the 2 possible sites of pain
- Cutaneous typically dominates since it is most used/recognized
major excitatory NT released by primary nociceptive sensory neurons
glutamate
types of glutamate receptors
NMDA, AMPA; ionotropic and activated by glutamate but different time course
- AMPA = rapid synaptic response
- NMDA - generate slower excitatory potential and require simultaneous depolarization and glutamate before associated channels open
- glutamate can evoke both fast and slower excitatory responses from postynaptic dorsal horn neurons depending on whether or not cell is depolarized
which part of triple response requires axon vs not
Bradykinin actions requires axon, but substance P does not
o Stimulation dependent enhancement of post-synaptic response of pain-activated dorsal horn neurons (due to initial activation of AMPA receptors then NMDA)
“wind up”
Result of activation of NMDA receptors
- triggers series of biochemical cascades leading to long-lasting changes in excitability
- NMDA phosphorylated by Protein kinase C (PKC) and tyrosine kinases– removes need for depolarization to activate NMDA receptors
Intense stimulation of C fibers leads to
release of glutamate and substance P
- Substance P binds to NK1 receptor – closes K channels –> depolarization
- Sub P lead to enhancement/prolongation of actions of glutamate
removal of glutamate and substance P from synapse
Glutamate taken up by nerve terminals/glia. Substance P has to diffuse out and interacts with neighboring neurons –>depolarizing and leads to broad central sensitization
2 mechanisms for producing analgesia
1- gate control mechanism
2- involves descending influences from higher CNS levels
Gate control theory
- nociceptive inputs open and
- balance between nociceptive and non-nociceptive inputs
- non-nociceptive afferents shut a gate that leads to central transmission of noxious information
- Essential aspect of gate control theory = anatomical specificity– segments of spinal cord in which nociceptive and non-nociceptive afferent s terminate are inked to same region of body
Dorsal Horn Synapse mechanism of analgesia
selectively stimulate large diameter Abeta fibers that leads to inhibition of dorsal horn synapse/reduction of pain by exciting inhibitory interneurons that decrease efficacy fof nociceptive dorsal horn synapses
- alternative method for activating Abeta fibers involves stimulation of dorsal columns
Descending control mechanism of analgesia
stimulation of periaqueductal gray region (PAG) produces powerful analgesia– touch, pressure, and temperature sensations persist and only pain sensation attenuated
- procedure called “stimulation-produced analgesia”
where do PAG neurons project
nucleus raphe magnus in medulla
what NT do PAG neurons release
serotonin
how to PAG neurons project to spinal cord
via dorsal lateral funiculus
What does serotonin do in spinal cord
serotonin leads to inhibition of second-order neurons of dorsal horn by exciting an inhibitory interneuron
- Interneuron uses enkephalin as its transmitter (endogenous opiate)
- Presynaptic inhibition by blockign voltage-gated Ca current
- postsynaptic inhibition– opens K channels
what is located at receptor end of C and Adelta fibers?
free nerve endings
Substance P release requires what?
repetitive stimulation
does glutamate release require one stimulus or repetitive
one –
Activation of NMDA receptors
need depolarization and glutamate; once they have been phosphorylated by things in post-syn cell will last a while plus there are more NMDA receptors are put into membrane –> hypersensitivity
Dorsal lateral funiculus
tract carrying nerve exons from PAG to dorsal horn
Opioid receptors
- found throughout CNS/elsewhere
- G-protein coupled
- several subtypes– activation leads to inhibition of neuron on which they are found
- variety of mechanisms involved (inhibit presyn Ca, open K postsynaptically)
- PAG has a lot of receptors
Cannabinoids
- CB1 and CB2 receptors (presynaptic)
- immune system involved
- lead to decreased secretion of pro-inflammatory /increased secretion of antiinflamatory agents
- lead to inhibition of release of neurotransmitters
- maybe this system also involved in stress-induced analgesia
Neuropathic pain
persistent pain syndromes– increased responses to noxious stimuli or nonnoxious stimuli
Na channels
TTX sensitive and TTX resistant
Central Mechanisms
- Loss of C fibers or injury in spinal cord –> Abeta fibers grow into area that used to be only C fibers in substantia gelatinosa, so now non-noxious stimuli cause pain
Neuropathic pain involvement of immune cells and glia
peripheral injury provokes inflammatory reactions at lesions site, DRG, and spinal cord
