Term
|
Definition
| primary afferent nerves with peripheral terminals that can respond differentially to noxious stimuli |
|
|
Term
| fiber types that carry signal to ascending pain pathways |
|
Definition
small, myelinated A-delta fibers
unmyelinated C fibers
speed of transmission C < A-delta |
|
|
Term
|
Definition
carry "fast pain" signal
able to differentiate the type of stimulus and accurately localize it
ascend via the "neospinothalamic tract"
perceived as a specific pain
carry analytical pain info |
|
|
Term
|
Definition
carry "slow pain"
not perceived as a very specific pain; dull, burning, or aching that is less well localized
ascend via the "paleospinothalamic tract"
carry behavioral data |
|
|
Term
|
Definition
high threshold mechanoreceptors that only respond to high/deep pressure
mechanothermal receptors that respond to temperature |
|
|
Term
|
Definition
| polymodal fibers that respond to mechanical, thermal and chemical signals |
|
|
Term
|
Definition
pain transfer via free nerve endings
often in muscle and viscera |
|
|
Term
|
Definition
| specialized organ for reception/transmission of pain |
|
|
Term
|
Definition
can receive mechanical, thermal and chemical signals
tend to send their signal via C fibers |
|
|
Term
transient receptor potential vanilloid 1
TRPV1 |
|
Definition
ligand-gated ion channel
can be activated by heat, and by capsacin (active ingredient in hot chili peppers) |
|
|
Term
| Na 1.7 voltage-gated sodium channel |
|
Definition
specific isoform of sodium ion channel coded for by the SCN9A gene
gene mutations affecting activity of this channel can cause abnormalities in pain reception
excess activity: familial primary erythromelalgia
decreased activity: insensitivity to pain |
|
|
Term
| familial primary erythromelalgia |
|
Definition
hereditary condition caused by a mutation in SCN9A that causes over activation of the Na 1.7 channel
causes intermittent burning pain, redness, heat, and swelling of the distal limbs in response to warm stimuli or mild exercise |
|
|
Term
| propagation of nociceptive signals |
|
Definition
| activated nociceptors generate an electrical signal that propagates down axon to dorsal horn of the spinal cord (orthodromic - in the right direction) |
|
|
Term
|
Definition
central projections of nociceptive afferents (A-delta and C fibers) terminate at different layers in the dorsal horn of the spinal cord and release neurotransmitters
after synapsing in the dorsal horn, the signal ascends to the brain via the spinothalamic tract |
|
|
Term
| nociceptive neurotransmitters related to ascending fibers |
|
Definition
A-delta fibers release glutamate
C fibers release glutamate AND substance P |
|
|
Term
|
Definition
pathway of C fibers
make diffuse, polysynaptic connections in cord gray matter
projections to VPN of thalamus and reticular formation
diffuse projections to the cortex (parietal, frontal, limbic regions)
affective and motivational aspects of pain |
|
|
Term
|
Definition
goes more directly from dorsal horn to VPN of thalamus, which then projects to the primary sensory cortex
somatotopic organization
rapid, accurate localization and perception of pain |
|
|
Term
descending pain modulating pathways
PAG |
|
Definition
modulate the ascending nociceptive pathways
PAG: periaqueductal gray (around cerebral aqueduct in midbrain)
-sends serotonin projections through RVM (rostral ventromedial medulla/raphe nuclei)
-projects to DLPT, which releases NE
-some dopaminergic processes too (role in addictive behavior, related to hypothalamus) |
|
|
Term
descending pain modulating pathways
DLPT |
|
Definition
PAG-->dorsolateral pontine tegmentum
releases norepinephrine from dorsal horn |
|
|
Term
descending pain modulating pathway
hypothalamus |
|
Definition
origin: periventricular posterior hypothalmaus
releases dopamine in dorsal horn of spinal cord |
|
|
Term
| 3 pathways of descending modulation |
|
Definition
serotonin, norepinephrin, dopamine
operate through interneurons or directly synapse onto C and A-delta fibers |
|
|
Term
nociceptor sensitization
definition |
|
Definition
after repeated application of a noxious stimulus, both A-delta and C nociceptors become more sensitive resulting in allodynia and hyperalgesia
pathway becomes more traumatized the longer it is exposed to pain at periphery and central level |
|
|
Term
|
Definition
aka hyperesthesia
pain resulting from a stimulus that would normally be innocuous
a manifestation of sensitization |
|
|
Term
|
Definition
stimuli that would normally be perceived as mildly painful are perceived as more intensely painful
manifestation of sensitization |
|
|
Term
| causes of nociceptor sensitization |
|
Definition
neurogenic inflammation
ion channel upregulation
(both are mechanisms of sensitization at the peripheral level) |
|
|
Term
|
Definition
aside form normal othodromic transmission down the nociceptive fiber, the signal also propagate antidromically down other axonal branches of the same neuron releasing peptides (e.g. substance P) from the terminals of the branches
causes an inflammatory response which is a noxious stimulus, further stimulating original nociceptor |
|
|
Term
|
Definition
| sensitization caused by upregulation of ion channels in response to repeated stimulation of the cell |
|
|
Term
|
Definition
re-organization of synaptic connections that the nociceptors make in the spinal cord
another mechanism for getting allodynia and hyperalgesia |
|
|
Term
nociceptive neurotransmitters
(list) |
|
Definition
substance P
glutamate
serotonin
norepinephrine
dopamine
opiates
GABA
(all of above are potential targets for medications that treat pain) |
|
|
Term
nociceptive neurotransmitters
substance P |
|
Definition
C fibers
released peripherally (causing inflammation) and in dorsal horn |
|
|
Term
nociceptive neurotransmitters
glutamate |
|
Definition
A-delta and C fibers
released in dorsal horn |
|
|
Term
nociceptive neurotransmitters
serotonin |
|
Definition
| released in descending inhibitory pathways releases from RVM (rostral ventromedial medulla<--PAG) |
|
|
Term
nociceptive neurotransmitters
norepinephrine |
|
Definition
| released in descending inhibitory pathways from DLPT (dorsolateral pontine tegmentum<--PAG) |
|
|
Term
nociceptive neurotransmitters
dopamine |
|
Definition
descending input to dorsal horn from periventricular posterior hypothalamus
also input to PAG from reward systems (role in addictive behavior) |
|
|
Term
nociceptive neurotransmitters
opiates |
|
Definition
| act both centrally and peripherally |
|
|
Term
nociceptive neurotransmitters
GABA |
|
Definition
| released by inhibitory interneurons int he dorsal horn |
|
|
Term
|
Definition
stimulation of nociceptive neurons
pain system doing its job
pain resulting from a stimulus severe enough to cause tissue damage |
|
|
Term
|
Definition
pain resulting from dysfunction of nerves in the nociceptive pathway
pain system not working correctly
brain perceives as if pain signals are being sent |
|
|
Term
features of neuropathic pain
(7) |
|
Definition
1. occurs int he absence of detectable ongoing tissue damage
2. includes a component of dyesthesias (abnormal or unpleasant sensations), frequently burning or electric
3. includes a paroxysmal component - shooting or stabbing
4. associated with allodynia
5. results in pronounced summation and after-reaction with repetitive stimuli
6. has a delayed onset after a precipitating injury
7. is felt in a region of sensory deficit |
|
|
Term
| possible mechanisms of neuropathic pain |
|
Definition
sensitization mechanisms
inflammation due to degenerating nerve cells
disinhibition of neighboring nociceptors
central reorganization |
|
|
Term
mechanisms of neuropathic pain
sensitization |
|
Definition
| same neurogenic inflammation and ion channel upregualtion mechanisms continue to operate as long as the nociceptive neurons are still functioning to some degree |
|
|
Term
mechanisms of neuropathic pain
inflammation |
|
Definition
the nerve injury itself can induce inflammation
inflammation stimulates surviving nociceptors in the area resulting in standard nociceptive pain |
|
|
Term
mechanisms of neuropathic pain
disinhibition |
|
Definition
| if nociceptors chronically inhibit their neighbors at baseline, it damaged setting these neighbors are DISinhibited and convey a nociceptive message to central pain centers |
|
|
Term
mechanisms of neuropathic pain
central reorganization |
|
Definition
can occur at the level of the spinal cord (analgous to central re-organization) or in the brainstem and above
seems to be the most likely explanation for the severe pain that some patients develop after a purely central process such as a thalamic stroke |
|
|
Term
complex regional pain syndrome
(reflex sympathetic dystrophy) |
|
Definition
condition that develops after a traumatic injury (mild or severe)
typical features of neuropathic pain plus a variety of local autonomic abnormalities:
-edema, temperature change, skin discoloration, trophic changes, hyperhydrosis |
|
|
Term
| general principles of pain management |
|
Definition
titrate analgesics to severity of pain
use regularly scheduled dosing, not "as needed"
use adjuvant medications
GOAL: complete pain relief (chronic low-level pain may cause sensitization) |
|
|
Term
gradation of analgesics
(first choice-->with increasing pain) |
|
Definition
NSAIDs
low-potency opioid analgesics (codeine, oxycodone, hydrocodone)
adjuvant meds (TCAs, NSRIs, antiepileptics)
high-potency opioids (morphine, etc) |
|
|
