CNS 3 (Pain + Headache + Anxiety+ Depression)

SEQ Action Potential

1. Resting Potential -70

2. depolarizing stimulus reach threshold -55

3. Na2+ channels open (rapidly depolorize until peak +30)

4. Once at peak K+ channels open and K+ and Na+ channels close

5. Hyperpolarization below threshold

6. Refractory period

7. K+ channels close

8. Back to resting (powered by ATP)

SEQ Neurotransmitter release starting with an action potential

1. action potential depolarizes axon terminal

2. Ca2+ channels open Ca2+ comes INTO presynaptic cell

3. Vesicles full of neurotransmitters leave with he help of Calcium and SNAP

4. neurotransmitters bind to receptors on post synaptic and can be excitatory and allow another action potential OR be inhibitory (GABA)

Sensory process that provides signals that trigger pain when in the presence of a NOXIOUS stimulus

nociceptors

Noicereceptors are located in the _______ on _______ nerve endings that innervate the skin

What are the three types?

periphery FREE
1. mechanical 2. chemical 3. thermal

Grey matter consists of

sensory and motor nuclei

1st Order Sensory Neurons: cell bodies in the DORSAL _______ ___________ (stimuli—>spine —> medulla)

2nd Order Sensory Neurons: synapse within the DORSAL ______ and release ____________ (medulla —> thalamus)

3rd Order Sensory Neuron: immediately ____________(cross) and ascend through the _______ _________ and brain stem to the __________

THEN projects to the somatosensory cortex in the __________ LOBE

ROOT ganglia

HORN release glutamate

decussate through spinal chord and brain stem TO THALAMUS

parietal

_________ is afferent and goes up the brain through the spinal cord and brain stem

_________ is efferent and goes down from the brain to the muscle

sensory

motor

what are the two pathways to pain?

spinothalamic and trigerminothalamic

in the Spinothalamic pathway, pain fibers decussate at the level of input to the _________ ________

in the Trigerminthalamic pathway pain fivers of the face and head decussate in the ____________

• spinal chord

• medulla

Dorsal Column System (TOUCH NOT NOCICEPTION):

First-order neuron enters at the dorsal _______ and ascends to the ________ in the dorsal columns

Synapses on the _________ order neuron on the same side in the medulla

_________ order neuron decussates in the ________ ______ (_________)

• ROOT medulla

• second

• third brain stem (medulla)

what is the difference between nociception and touch? which system in specific to touch and which is specific to noiciception?

nociception level of injury goes up to spinal chord then brain stem (medulla)

touch : goes straight up to medulla (brain stem)

Touch fibers decussate in the ______________

Pain fibers decussate at _______________________ to the ___________________

• touch = medulla

• pain = level of input to spinal chord

Ipsilateral and contralateral are types of

Disassociated Sensory Loss

which dissociated sensory loss deals with

DECREASED TOUCH sensation

NORMAL PAIN sensation

how is one able to still feel pain?

ipsilateral

site of injury (loss of sensation) is on the same side where pain is felt

which dissociated sensory loss deals with

DECREASED PAIN sensation

NORMAL TOUCH sensation

Contralateral

ipsilateral is when the responsive reaction is on the same/opposite side of the injury

SAME

feeling of pain at a site separate from where an injury

ex. pain in left shoulder is sign of heart attack

Referred Pain

REFFERED PAIN EXAMPLES:

internal organ injury vs body pain

1. liver —>

2. lung cancer —>

3. kidney stones —>

1. shoulder blades

2. shoulder pain

3. lower back, abdomen, sides

referred pain is due to the brain improperly processing pain input from an _________ organ as _______pain

internal

body

brain freeze is an example of _________

how?

reffered pain

brain detect cold as pain

stimulation of nociceptor triggers

action potentials

what happens when the nociceptor triggers action potentials but the Sodium (Na2+) channels are mutated

which sodium channel is specific to nociceptor action?

loss of pain OR extreme pain

• Nav1.7

abnormal loss of function of nociceptors lead to

CONGENITAL insensitivity to pain (feel no pain bc/ Na+ blocked not allowing postsynaptic neuron to depolarize)

abnormal gain of function of nociceptors lead to

POROXYSMAL EXTREME pain

hypersensitivity more FREQUENT action potential not stronger (bc/ all or none response)

pain from physical damage

• goes away as injury heals

• responsive to opiates

nociceptive pain

Nueoropathic Pain:

• pain caused by neurologic ________ or __________

• pain is chronic with/without a specific stimulus or injury

• _________ limb pain and chronic ________ ______ pain

• damage or dysfunction (normal translate to pain)

• WITHOUT

• phantom lower back

are neuropathic and nociceptive pain exclusive?

NO you can have both at the same time

what are the two pain symptoms of of neuropathic pain and what are they caused by?

1. Allodynia: no injury but the brain senses pain

2. Hyperalgia: heightened perception of pain and increased persistence

are the following caused by alllodynia or hyperalgia?

• sharp, shooting, searing, or stabbing pain

• tingling sensations

• numbness

• extreme sensitivity to touch

• insensitivity to heat or cold

• muscle weakness

• worse pain at night

hyperalgesia

increased perception and persistence of pain

DIABETIC PERIPHERAL NEUROPATHY:

• primarily affects the ______ and _______, sometimes also hands and arms

• often begins with __________, weakness, burning, and ____________

• pain can be worse at ________

• blisters, sores, falls, mental health (depression)

• leading cause of ___________ in people with diabetes

• feet and legs

• numbness, tingling

• night

• AMPUTATION

what can increase your risk of experiencing diabetic neuropathy?

• smoking

• drinking

• hypertension

• obesity

• high cholesterol

• kidney disease

What are the three mechanisms of diabetic peripheral neuropathy?

1. microvascular changes

2. hyperexcitability of sensory neurons

3. inflammation

how do microvascular changes lead to diabetic peripheral pathology ?

damage to blood vessels

essential nutrients in blood don’t reach neurons

increased expression of voltage-gated ______ at terminals of nociceptive pain fibers

and

decreased expression of _________ ____________ channels in axons

lead to diabetic peripheral nueropathy

Na2+

shaker potassium

pro-inflammatory ________ in spinal chord enhance excitability within the ____________horn

microglia

DORSAL

Diabetic Neuropathy Treatment:

1. Lidocaine (topical anesthetic): antagonist/agonist of voltage-gated sodium channels

2. _________ reuptake of Norepinephrine in the spinal cord

3. Gabapentin: inhibits synaptic voltage-gated __________ channel by disrupting the regulatory function of a channel subunit

1. ANTAGONIST so pain action potential cannot go through

2. BLOCK (NE stay longer)

3. CALCIUM (prevent calcium from triggering neurotransmitter release that causes pain— glutamate )

1. lumbar spinal chord (input decussates)

2. cervial spinal chord (input decussates)

3. caudal medulla

4. _____________ tract

5. ventral posterior lateral nucleus of the thalamus

the following describes which sensory pathway?

SPINOTHALAMIC

1. claudal medulla

2. ponds

3. ventral posterior medial nucleus of the thalamus

which sensory pathway does this describe?

injury in what areas would lead to the pathway?

TRIGEMINOTHALAMIC

head, face, teeth

what is the difference between secondary and primary headaches?

primary - pain caused by headache

secondary - pain in another area causes headache

• migraine

• tension headache (HATBAND)

• hypnic headache (nighttime headache)

• cluster headache (short-lived one-sided; stuffy nose, tearing, enlarged pupils, droopy eyelids)

• inflammation of pain-sensitive areas in and out of the neck and head

are the following PRIMARY or SECONDARY headaches?

PRIMARY

pain caused by HEADACHE

• brain tumors

• aneurysms

• meningitis

• neck or head injuries

are ________ headaches

what does that mean

what is the actual headache like?

SECONDARY

headache as a sign of underlying conditions

start SUDDENLY very painful

Migraines:

• primary or secondary headache?

• long-term or episodic?

• Allodynia or Hyperalgia

• involves a network of multiple _______, _______, and ________ regions of the brain

• primary

• episodic

• allodynia (pain when not pain)

• cortical, subcortical, brainstem

what is the difference between migraines with aura vs without aura?

with aura: visual symptoms, hallucinations, phono and phototopia

do migraines with or without aura cause

• sensitivity to light (photophobia)

• sensitivity to sound (phonophobia)

• unilateral pain (affect only one side)

WITHOUT aura

do migraines with or without aura cause

• hallucinations

• scotoma (blind spot)

• motor/speech deficit

• flashing lights

WITH aura

SEQ migrane phases

1. premonitory (prodromal)

2. aura

3. headache

4. postdromal

Migrane Phases:

1. Prodronal: food cravings, _______ changes, uncontrolled ___________, fluid __________or increased ____________

2. Aura: flashing or bright lights that look like ________ _______, sensation of being touched or grabbed

3. Headache: starts ________ and builds in intensity

4. Postdromal: ___________ or ___________following a migraine. can take up to a _____ for people to feel healthy again

1. mood, yawning, retention, urination

2. heat waves

3. exhaustion confusion day

Migraines:

• are women or men more affected by migranes?

• when are migraines most frequent?

• patients are typically __________—______ between attacks

• women

• morning, before period, stressful week

• symptom-free!

Migranes have multifactoral polygenic inheretance meaning many mutated genes lead to a single phenotype

Mutations to what genes lead to the hypersensitivity experienced in migraines?

How does each normally function?

CACN1A —>Ca2+ channel

ATP1A2—> Na2+/K+ gradient

SCN1A—> action potential

Are CACNA1A mutations exclusive to familial hemiplegic migraines?

are there single mutations to CACNA1A or are there multiple?

post-synaptic

NO it can also be non-familial as well

multiple mutations of CACNA1A

mutations of ________ can lead to overactive or underactive Ca2+ channels

what role does Ca2+ channels play in neurotransmission?

CACNA1A

allow neurotransmitters to leave presynaptic and bind to postsynaptic receptors which can depolarize (Na2+) or repolarize (Cl-) depending on the neurotransmitter and rececptor

Migraines are caused by activation of nerves within the wall of the _______ _______ vessels traveling inside the __________

dilation/constriction of these blood vessels causes pain

• brain blood

• meninges (protective layer)

DILATION OF MENINGES BLOOD VESSELS IS BRAIN CAUSES PAIN

• the activation of the ________________ _________ (TGVS) causes the blood vessels of the meninges to dilate

• peripheral axons from the ______________ ____________innervate (supply nerves to) the meninges and intracranial blood vessels

• Activation of these fibers leads to the release of neuropeptides, including the ___________________ (CGRP)

• This neuropeptide will then bind to both __________ _________ and _________ ________ fibers

• TriGeminoVascular System

• trigeminal ganglion

• Calcitonin Gene Related Peptide (CGRP)

• blood vessels and nociceptor pain

Define the GENERAL mechanism of migranes

Trigerminalvascular system—>

CGRP —>

Blood Vesssel (DILATE) + Noiceptor Pain fiber

Preventative pharmaceutical treatments against migraines including erenumab

inhibit the ___________ binding site in the ________ receptor to prevent the ligand from binding to the receptor

overall preventing ____________

CGRP

vasodilation of the meninges

Acute treatment:

Ergot Derivatives: a- adrenergic and serotonin agonist/antagonist?

Triptan: seretonin ____________

Lasmidtan (Reyvow): ________ receptor agonist

Ubrogepant (Ulbrelvy): ________ receptor ANTAGONIST, inhibits vasodilation as well as transmission of pain signal

• AGONIST bc/ they both result in vasoconstriction

• Agonists

• Seretonin

• CGRP

Acute Treatments Continued:

Nonprescription ______________

Combination __________ and __________ (vasoconstriction)

Prescription ____________

Nausea relief (SETRON)

Narcotics

analgesics

analgesics caffein

NSAIDS

Behavioral state neurons:

• reticular formation of the _______ _________

• __________________

• _______ system (emotions)

• brain stem

• hypothalamus

• limbic

The modulators of Sensory and Cognitive Processes:

• ______/________ cycles

• attention

• arousal

• modulation of _______ tone

• ability to ________

• sleep/wake

• muscle tone

• focus

4 diffuse modulatory systems originate in the ______ _______of the brain stem

Project ___________ to large areas of the brain

reticular formation

axons

What are the 4 diffuse modulatory systems of the Behavioral State Nuerons

1. Noradrenergic (norepinephrine)

2. Serotonergic

3. Dopaminergic

4. Cholinergic

Major Depressive Disorder:

• how long do they last?

• what is anhedonia?

• comorbidities: is it often associated with other disorders?

• can genetics impact your risk?

• daily for 2 weeks or longer

• less sensitive to pleasure

• yes. ex. a person with cancer will most likely experience a major depressive disorder

• yes BUT no DNA marker to make a diagnosis

Major Depressive Disorder:

• level of __________ is less important than how it acts in the synapse (will it bind to post-synaptic receptors)

• _______ is a type of ____________

• seretonin

• seretonin = MONOAMINE

Major Depressive Disorder: ___________ depletion hypothesis

• MDD deals with decreased signaling within monoamine (________________, _______________, ______________)

• Proposed when 20% of people taking _______ for _________ became depressed

• Supported by observed side effects of ____________ __________ inhibitors (imipramine, ) to relieve defensive

• lower levels of serotonin ______ in CHS of people with MDD

• diets low in _________ can cause symptoms to return

• many drugs that treat ______ act to increase _________ and/or availability

• monoamine

• 5HT, Norepinephrine, and Dopamine

• reserpine for hypertension

• monoamine oxidase

• metabolites

• tryptophan

• MDD serotonin

what are some other systems besides increasing serotonin that help treat MDD: __________ systems + ________+ ________ ______-

glutamatergic

cortisol

HPA axis

what is used to treat Major Depressive Disorder:

• Monoamine Oxidase Inhibitors

• Reuptake Inhibitors

• Ketamines

Reuptake Inhibitors prevent monoamines from going back into the presynaptic neurons and keep them at the synapse

________ prevent the reuptake of 5HT

________prevent the reuptake of dopamine

___________prevent the uptake of Norepinephrine

__________ prevent the reuptake of 5HT and NE

___________ prevent reuptake of Norepinephrine and Dopamine

5HT= SSRIs

Dopamine = DAT

NE = NET

5HT and NE = SNRIs

NE and DA = NDRIs

Ketamines are NMDA receptor antagonist/agonist

Avuelity: combination bupropion (Wellbutrin) and _____________________

antagonist

dextromethorphan (DM)

do you have a panic disorder if you have panic attacks?

no, the panic attacks must be RECCURING to be considered to have panic disorder

a period of extreme fear or discomfort that develops and reaches a peak within 10 minutes

panic attack

a relatively continuous state of excessive uncontrollable and pointless worry and apprehension; constant state of feeling overwhelmed, accompanied by fear and worry

• is it apart of a bigger disorder?

• how long does it occur?

generalized anxiety disorder

• NO

• 6 months

Mechanism of Anxiety Disorders:

• are there genetic risks involved?

• abnormal activity of _____ in the locus __________ (BRAINSTEM NUCLEUS BLUE SPOT)

• inappropriate activation/inactivation of flight or fight response

• yes

• NE in locus coeruleus

• activation

Sympathetic Nervous System

neurotransmitter =

receptor types =

• Norepinephrine

• a and b adrenergic

Parasympathetic Nervous System:

nuerotransmitter:

receptors:

Ach

nicotinic and muscarinic

Anxiety Disorder Treatments:

• Benzodiazapenes: GABA receptor antagonist/agonist (xanax, valium)

• B blockers: competitive antagonists for _________ and __________ on adrenergic beta receptors of the sympathetic nervous system (propanol)

• Anti-Anxiety: selective _________ receptor agonist (buspirone)

• Antidepressants such as ________ Inhibitors such as _________ and ___________

• GABA agonist

• norepinephrine and epinephrine

• serotonin

• reuptake (SSRIs + SNRI) — seretonin and norepinephrine reuptake inhibitors