Lec 16 Pain Flashcards
What does it mean that there are discriminative and affective components of pain?
- discriminative = ability to perceive and localize
- affective = behaviors and emotions that affect mood and motivation
What is the discriminative pain pathway?
- Ad + C fibers from body branch up and down a few segments [lisshauer’s tract] and synapse in dorsal horn [lamina I/V], cross immediately after synapsing, ascend in spinothalamic tract
- Ad + C fibers from face come from CN V, go caudal through spinal trigeminal tract, synapse in spinal trigeminal nucleus, cross immediately after synapsing, ascend in trigeminothalamic tract
- all fibers join together and synapse in VP thalamic nuclei then go to S1
What is the affective path of pain perception?
- originates from ascending info from lamina I/V in dorsal horn or spinal nucleus of V
- travels through spinothalamic/trigeminothalamic tracts
- axon branches innervates a bunch of things along the way
periaqueductal grey [PAG]
rostroventral medulla [RVM]
thalamic VM and MD nuclei
ventromedial hypothlamaus {VMH]
amygdala
globus pallidus
What is contained in the rostroventral medulla [RVM]?
- parabrachial nucleus [pons]
- reticular formation
- raphe nuclei
Where do fibers that branch of off spinothalamic fibers into thalamic VM and MD nuclei project to? function?
- project to insula and cingulate cortex
- encode emotional components of pain that affect mood and motivation
What is the role of periaqueductal gray [PAG] and RVM [rostroventral medulla] in control of pain?
- receive collateral fibers off of spinothalamic tract that feedback into PAG and directly activate descending projections
- integrate “top-down” info from cortex [S1, cingulate, insula] and limbic systems [amygdala and VMH] with ascending spinothalamic info
Where do PAG axons project? And what is the path by which they eventually effect spinal cord interneurons?
descend and synapse onto
- norepinephrine neurons in locus ceruleus and
- serotonin neurons in dorsal raphe
- after synapse, send projections to spinal cord dorsal horn where release NE/5HT onto local inhibitory interneurons
- local interneurons release enkephalin [endogeneous opioid] to inhibit lamina I and V spinothalamic neurons –> thus decrease throughput of nociceptive transmission
What is function of enkephalin?
acts both pre and post synaptically
pre: pain/temp A-delta and C fibers –> inhibits NE release
post: spinothalamic ascending neurons –> causes hyperpolarization, diminishing ESPs
What structures are responsible for emotional content of pain?
limbic
- amygdala + insula
what 3 structures are responsible for motivational content of pain?
- globus pallidus
- cingulate
- S1
what structure is responsible for generating appropriate behaviors to threats?
ventromedial hypothalamus [VMH]
what happens in nociceptive pain syndrome?
- first pain mediated by A-d, 2nd pain by C
- gate theory: spinothalamic nerves receive convergent input from Ad/C and AB fibers, AB fibers can activate inhibitory interneuron which dampens throughput of pain info from Ad/C
= due to cross-talk
- no nervous system lesion or inflamation
- dampened feeling of pain from Ad/C due to inhibition by AB fibers that are close by
- referred pain from visceral site of lesion to a far away cutaneous site
- only pain in presence of stimulus [no pain with lack of stimulus or with light touch]
what happens in inflammatory pain syndrome?
- pain hypersensitivity due to peripheral inflammation involving detection of active inflammation by nociceptors and a sensitization of nociceptive systme
- spontaneosu and stimulus dependent pain
- evoked by low and high intensity stimuli
= protective –> aids in healing in tissue trauama or joint inflammation
mech: neurochemical mediators secreted by immune cells cause pain fibers to discharge APs aberrantly –> peripheral and central amplification of pain
What is allodynia?
normally non-painful stimuli become painful
What is hyperalgesia?
exaggerated response to normally painful stimulus
What is disfunctional pain?
s
What stimuli cause inflammatory pain?
tissue trauma, surgery, joint inflammation [rheum arthritis]
What stimuli cause nociceptive pain?
- abnormal mech forces, organ injury [angina, ischemic claudication]
What is dysfunctional pain?
maladaptive pain – neither protects nor upports healing/repair
- same components as inflammatory pain without evidence of inflammation or neuronal lesion
- spontaneous and stimulus dependent
- get sensory amplification
What are examples of stimulus that can cause dysfunctional pain?
fibromyalgia [body wide pain in joints/muscle, central amplification]
primary erythermalgia [peripheral amplification of pain, red/war/burning in hands and feet
What is neuropathic pain?
- maladaptive plasticity caused by lesion or disease alters nociceptive processing so that pain is felt in absence of stimulus and responses to innocuous/noxious stimuli are enhanced
- have hyperalgesia, allodynia, pain that outlasts stimulus
What are mechs that might cause neuropathic pain?
CNS: stroke, spinal cord injury, multiple sclerosis
PNS: nerve trauama, metabolic [diabetes], herpes zoster, AIDS
What is central sensitization? mech?
- synaptic signaling strength of pain pathways greatly exaggerated by several maladaptive mech
- causes pain to no longer be coupled so tightly to presence/intensity/duration of noxious peripheral stimuli
- produces pain hypersensitivity of normal inputs
What are 3 possible mechs leading to central sensitization
- increased membrane excitability in peripheral axons via upregulation of Na channels
- increased synaptic efficacy via upregulation of glutamate receptors at 2nd order neurons
- decreased inhibition in local interneuron networks, decreased inhibition by descending systems
What is phantom limb pain?
pain in body part that has been amputated
2 mech:
- arises from central sensitization
- cortical reorginization of S1 – axons from neighboring cortex sprout into region of cortex that previously received input form amputated limb, causes axon firing unpredictably –> pain
What are treatments for neuropathic pains?
- give antidepressants [MAO reuptake inhibitors, improve MAO descending inhibition path]
- give anticonvulsants [block ectopic discharge]
- block neurotransmitter release [ Ca channel anticonvulsants]
- opioids [enhance endogenous inhibitory analgesic system]
-
what does inflammatory pain respond to?
- often NSAIDs, other anti-inflammatory agents
What are pitfalls of opioids?
addiction
tolerance
overuse
cognitive impairment
