31 pairs, 4 segments

1. cervical: C1-C8

2. thoracic: T1-T12

3. lumbar: L1-5

4. sacral: S1-S5

(5. coccygeal: 1 unpaired nerve)

-spinal cord starts at foramen magnum > ends at L1 where it tapers into conus medullaris > after that is the cauda equina (horse's tail)

-cervical enlargement and lumbar enlargement: areas of lots of nerves coming in and out

at the top: dura mater attaches to the rim of foramen magnum

at the bottom: pia mater attaches to the coccyx/tail bone > filum terminale

at the sides: denticulate ligaments: pia mater attaches to the dura mater on the sides, 21 pairs of tooth like ligaments

-consists of axons, schwann cells and connective tissue surrounded by epi > peri > endoneurium

-epineurium is continuous with dura mater

spinal cord > rootlets > 6-8 rootlets merge into dorsal/ventral root > roots merge into spinal nerve > divides into dorsal/ventral ramus

found in the dorsal root ganglion (cell bodies of sensory neurons)

-technically pseudounipolar cells > cell body has 1 axon which becomes 2 axons (not really a dendrite)

motor to the muscles of the back and the skin

sensory of these regions also

-looks like a butterfly

-3 horns

1. posterior/dorsal

2. lateral

3. anterior/ventral

gray matter = cell bodies

white matter = myelinated axons

3 columns surrounding the gray matter

1. dorsal

2. ventral

3. lateral

anterior median fissure

posterior median sulcus

central canal: holds CSF to cushion the brain and provide nutrients

gray/white commissure fibers: axons that cross from one side of the spinal cord to another

1. sensory receptor detects a stimulus

2. sensory neuron conducts AP's through the nerve and dorsal root to the spinal cord

DORSAL = SENSORY

3. SITE OF DIVERGENCE: at the spinal cord the sensory neuron synapses with an interneuron which synapses with a motor neuron AND/OR sends a branch through an ascending tract to the brain

4. SITE OF CONVERGENCE: interneuron synapses with motor neuron AND/OR descending tract from the brain synapses with the motor neuron

5. motor neuron axon conducts AP's through the ventral root and spinal nerve to an effector organ (skeletal muscle)

VENTRAL = MOTOR

dorsal column is composed of 2 ascending tracts to the thalamus

1. fasciculus cuneatus: wedge shaped, more lateral

2. fasciculus gracilis: thin ribbon, more medial

information about

1. 2 point discrimination

2. proprioception

3. pressure

4. vibration

ascending tracts (spinothalamic, spinoreticular, spinomesencephalic tracts) with information about

1. pain

2. temperature

3. light touch

4. pressure

5. tickle

6. itch

corticospinal tracts (descending): motor cortex to the spinal cord

head movement

diaphragm movement

neck and shoulder movement

upper limb movement

thoracic (rib) movements in breathing

tone in postural back muscles

movement of vertebral column

dermatome = area of skin supplied with sensory innervation by a pair of spinal nerves

ALL EXCEPT C1

cervical nerves get injured because they are stretched or pulled or torn

-cervical/thoracic nerves damaged > look at dermatome and will see that area of skin is painful

anasthesia: loss of sensation because of the nerve compression

-caused by the herpes zoster virus > chicken pox virus

-neurogenic inflammation!

-the virus remains dormant in the dorsal root ganglion cells > reactivated by some factors (compromised immune system, stress, unknown)

-reactivated virus causes inflammation in the dorsal root ganglion nerve > causes inflammation/blisters/eruptions/itching at the skin innervated by that sensory nerve

-common nerves affected: back of the neck, head, sides of belly

pain after the herpes zoster infection has subsided

-the zoster virus damages the sensory nerve fibers > continual pain

-sometimes the fibers can heal, but sometimes it is permanent

general: somatic or visceral

somatic: touch, pressure, proprioception, temperature, pain

visceral: pressure, pain from internal organs

special: smell, taste, sight, hearing, balance

stimulus: compression, bending or stretching of cells

senses: touch, tickle, itch, vibration, pressure, proprioception, hearing, balance

stimulus: ligand-receptor interaction

senses: smell and taste

stimulus: light receptor interaction

sense: vision

stimulus: intense mechanical, chemical and thermal stimuli

sense: pain

free nerve endings

merkel's disc

hair follicle receptor

pacinian corpuscle

meissner corpuscle

ruffini's end organ

located in epidermis

pain

itch

tickle

temperature

joint movement

proprioception

located just underneath the surface of the skin

light touch

superficial pressure

located wrapped around hair follicles > can be attached to more than 1 follicle

light touch

responds to very slight bending of the hair

located deep int he dermis or hypodermis

structure: like an onion, wrapped around in the lamellae: layers of schwann cells that encapsulate the nerve fiber > need stronger stimulation to activate

deep cutaneous pressure

vibration

proprioception

located throughout the dermal papillae > bulbous 

2 point discrimination: sense of stereognosis > distance between 2 points that a person can detect as separate points of stimulation

located in the dermis, primarily fingers

continuous touch or pressure

responds to depression or stretch of skin

1. receptor density > meissner's densely located in the tongue and fingertips but diffusely located in the back and shoulder

2. receptive fields: inversely related to receptor density > lots of meissner's corpuscles in the finger > dendritic tree "listens" to a small area

3. strength of signal > amplitude of receptor potential/depolarization

4. receptor potential governs frequency of AP which is intensity of stimulus

slowly adapting receptors

ex. free nerve endings

generate AP's as long as a stimulus is applied and adapt very slowly > produces AP along the duration of a stimulus

rapidly adapting

ex. pacinian corpuscles, NOT PAIN FIBERS

adapt rapidly and are most sensitive to changes in stimuli > response happens quickly and then stops

-like wearing a watch > put the watch on and feel the stimulus but while you wear it you can't feel it anymore

NT release > leads to hypopolarization or hyperpolarization > can range anywhere from +30 to -100 mV > analog scale

AP depends on if the level of depolarizations reaches threshold > either goes on or off > digital scale

SUBTHRESHOLD: depolarization from stimulus does not meet the threshold

THRESHOLD: warm stimulus > few AP

SUBMAXIMAL > warmer stimulus > more AP generated

MAXIMAL > very hot stimulus > max AP generated

SUPRMAXIMAL > scalding hot stimulus > max AP generated still

changes in the amount of depolarization (analog) leading to changes in number of AP generated (digital) > 111111

primary: located in the dorsal root ganglia, synapse with interneurons

secondary: interneurons synapse with secondary neurons, cross to the contralateral side of the spinal cord through the anterior portion of the gray and white commissures and enter the spinothalamic tract  > ascend to thalamus

tertiary: secondary synapses with tertiary in the thalamus > project to somatic sensory cortex

sense: light touch, pressure, tickle, itch

1. merkel disc stimulated > generated AP to the primary neuron > dorsal horn

2. primary neurons synapses with interneuron > crosses to other side and synapses with secondary neuron (anterior spinothalamic tract)

3. anterior spinothalamic tract joins the lateral to become the anterolateral spinothalamic tract which synapses to a tertiary neuron in the thalamus

4. tertiary neuron > somatic sensory cortex

-primary neuron can send divergent signal to higher levels of the spinal cord

-multiple merkel disks converge into the same anterior spinothalamic tract > cannot discriminate light touch well

sense: pain, temperature 

1. free nerve ending stimulated and sends AP down the primary neuron into the dorsal root

2. primary neuron synapses with an interneuron and the interneuron synapses with a secondary neuron on the opposite side > CONTRALATERAL

3. secondary neuron (ascending lateral spinothalamic tract) travels to medulla, pons, midbrain

4. secondary synapses with a tertiary neuron at the thalamus > somatic sensory cortex

medial lemniscus: continuation of the dorsal column in the brainstem

senses: 2 point discrimination (meissner's corpuscle), proprioception (pacinian's corpuscles)

1. joint movement on left side > pacinian corpuscle fires AP's to primary neuron > dorsal horn

2. primary neuron ascends on SAME side (ipsilaterally) and reach the medulla oblongata

3. primary synapses with secondary neuron at the medulla and cross to the opposite side of the cord at the decussation of the pyramids

4. secondary neuron travels up to the thalamus and synapses with tertiary neuron

5. tertiary neuron > somatic sensory cortex

proprioception

balance

1. joint movement on L side > pacinian corpuscle fires AP's to primary neuron > dorsal horn

2. primary neuron ascends on SAME side (ipsilaterally) but can't reach the medulla

3. LOSE 2 POINT DISCRIMINATION/PROPRIOCEPTION ON THE SAME SIDE OF HEMISECTION BELOW THE HEMISECTION

1. R cortex sends descending corticospinal tracts down to the spinal cord

2. corticospinal tracts crosses at the decussation of the pyramids at the medulla

3. corticospinal tract cannot make it down to the left side

4. LOSE MOTOR FUNCTION ON THE SAME SIDE OF THE HEMISECTION, BELOW THE HEMISECTION

1. light touch on R side > merkel disc stimulated > generated AP to the primary neuron > dorsal horn

2. primary neurons synapses with interneuron > crosses to other side and synapses with secondary neuron (anterior spinothalamic tract)

3. anterior spinothalamic tract joins the lateral to become the anterolateral spinothalamic tract but cannot make it to the thalamus

-primary neuron can send divergent signal to higher ONLY HAVE IMPAIRMENT OF LIGHT TOUCH ON THE OPPOSITE SIDE OF THE HEMISECTION, BELOW THE HEMISECTION

-travel up the spinal cord via the lateral spinothalamic tract

-primary neuron is unmyelinated and very thin > slow to get to the thalamus

acute: of sudden onset and subsides quickly once cause is removed and healing is established

chronic: lasts greater than or equal to 6 mo and persists even after healing has apparently completed

causes: parkinson's, MS, stroke, CVD, angina, kidney disease, etc.

1. low back pain: MOST COMMON

2. arthritis

3. angina: radiating pain up the neck and left arm

4. headaches

A. tension: tension at the back of the head

B. cluster: searing pain around the eyes

C. migraine: unilateral

5. trigeminal neuralgia

6. central pain syndrome/causalgia

sensory: burning, pricking, stabbing, aching

affective (emotional): hurting, depression

autonomic: change in HR, BP and perspiration

motor: vocalization, withdrawal responses

survival value: alerts organisms of tissue injury

tissue damage causes release of K+, 5HT (serotonin), bradykinin (BK), histamine, prostaglandins (PG), substance P (SP)

-K+, 5HT, BK, histamine, SP ACTIVATE PAIN FIBERS (causes fibers to fire AP's)

-PG SENSITIZES PAIN FIBERS

BK causes PG release > leads to inflammation > makes the blood vessels leaky, release of WBCs

SP released from synaptic terminal which activates pain fiber > positive feedback mechanism > leads to hyperalgesia

SP stimulates histamine release from mast cells > causes vasodilation, edema and extravasation = neurogenic inflammation

histamine: sensation of itching

Adelta fibers: mediate sharp localized pain

1-6 micrometers

thinly unmyelinated

conduct AP's at 5-36 m/s

C fibers: mediate dull, poorly localized, diffuse pain

0.2-1 micrometers

unmyelinated

conduct AP's at 0.2-1m/s

mechano-nociceptors (Adelta and C)

thermo-nociceptors (Adelta and C)

polymodal nociceptors (C)

-located in the dorsal horn of the spinal cord in lamina I and lamina II

-lamina II = substantia gelatinosa

-cells are inhibitory interneurons

-involved in pain pathways

1. pain from HEART enters at T1 > primary neuron > interneuron > contralateral secondary neuron (lateral spinothalamic tract) > tertiary neuron at thalamus > somatic sensory cortex

2. pain from L ARM enters at T1 > primary neuron > interneuron > SYNAPSES WITH THE SAME CONTRALATERAL SECONDARY NEURON 

overtime the brain will not be able to distinguish between the 2 sources of pain stimuli

nociceptive primary afferents have 2 branches: 1 branch eventually synapses with the lateral spinothalamic tract, 2nd branch inhibits the inhibitory interneurons of the substantia gelatinosa > PAIN GOES THROUGH

1. PGAM and RN descending tracts

2. brain sends descending tracts > can inhibit the lateal spinothalamic tract itself

3. large diameter mechanoreceptors (light touch, light pressure) stimulated > sends signals up the anterior spinothalamic tract and collateral branch stimulates substantia gelatinosa > MASSAGE, ACUPUNCTURE

caused by:

electrical stimulation of substantia gelatinosa

electrical stimulation of supra spinal regions (PAGM, RN)

TENS: transcutaneous electrical nerve stimulation

gate control theory

pain on L side > primary neuron enters dorsal horn > synapses with interneuron > synapses with contralateral secondary neuron/lateral spinothalamic tract > synapses with tertiary neuron > thalamus > somatic sensory cortex

1. branch from lateral spinothalamic tract to the PGAM (periaqueductal gray matter), PGAM also receives descending tract from the thalamus and cortex

2. PGAM neurons descend to the RN (raphe nucleus) > descend via the dorsolateral funiculus to the dorsal horn

3. descending tract releases 5HT and norepi to activate substantia gelatinosa > CLOSED GATE

intractable and chronic pain below the level of an amputation 

1. damaged nerve and its regrowth leads to abnormal and painful discharge at the stump

2. regrowth changes the way nerves from amputated limb connect in the spinal cord

3. changes in brain because of loss of sensory input from amputated limb

4. changes in body map of the brain

NSAIDS: block COX enzymes at site of tissue injury > prevent prostaglandin release and inflammation

local anesthetics (caines): Na+ channel blockers > prevent AP conduction > no pain below affected nerve

opiates: stimulate the inhibitory interneurons in the

substantia gelatinosa by acting on endogenous opiate receptors, stimulates entire neuroaxis, causes euphoria

acetaminophen: don't know

-PNS, SNS and sometimes ENS

-control center in the periventricular zone of the hypothalamus > around the third ventricle

-operates over extended time and space

 motor: motor cortex sends corticospinal tract which crosses over at the decussation of the pyramids and reaches the cord and comes out the ventral root > effector muscle

sensory: fibers enter through dorsal root ganglion > synapses with ascending tract on opposite side > thalamus > somatic sensory cortex

1. autonomic nuclei in the hypothalamus = periventricular > send tract down the lateral columns > synapse with preganglionic neuron > exit out the ventral root

2. craniosacral division: preganglionic neurons located in brainstem (CN III, VII, IX, X) and lateral horn of the sacral region of the spinal cord (S2-S4) (pelvic nerves)

3. long preganglionic neurons synapse with terminal ganglia (type of autonomic ganglion) located directly on the effector organ

4. terminal ganglia allow for communication between ganglia to modulate response and integrate info

5. short postganglionic fiber innervates effector organ

ciliary muscle

tear and salivary glands

heart

bronchi

lungs

stomach

pancreas

intestines

rectum

ureter

bladder

1. autonomic nuclei in the hypothalamus = periventricular > send tract down the lateral columns (specifically the intermediolateral column)> synapse with preganglionic neuron > exit out the ventral root

2. thoracolumbar division: nerves from T1 to L2 > short preganglionic fibers reach the chain ganglia (type of autonomic ganglia) found on each side of the spinal cord

-DIVERGENCE: 1 preganglionic fiber can give rise to 20-30 postganglionic fibers

preganglionic fiber out the ventral root > white ramus communicans > chain ganglia

1. can stay at the same level/go up/down the chain ganglia synapse with postgangionic fiber and exit out the gray ramus communicans > spinal nerve

preganglionic fiber > out ventral root > white ramus communicans > to the chain ganglia 

1. stays at the same level/goes up > preganglionic fiber synapses with postganglionic fiber at the chain ganglia and exits as a sympathetic nerve

preganglionic fiber > out ventral root > white ramus communicans > to the chain ganglia 

1. DON'T SYNAPSE AT CHAIN GANGLIA > just pass through to collateral ganglia > synapse with postganglionic fiber at collateral ganglia > splanchic nerve > viscera

collateral ganglia = celiac, superior/inferior mesenteric

preganglionic fiber > out ventral root > white ramus communicans > to the chain ganglia

1. DON'T SYNAPSE with chain ganglia > pass through to collateral ganglia DON'T SYNAPSE WITH THESE EITHER

2.  preganglionic fiber reaches the adrenal gland and synapses with cells in the adrenal medulla > stimulated adrenal medulla cell releases norepi and epi

eye

tear

salivary gland

blood vessel in head and neck

sweat gland

pilorector muscles

heart

bronchi

lungs

diaphragm

liver

stomach

pancreas

intestines

rectum

ureter

bladder

modified postganglionic cells > ONLY CELL BODIES > short axons

secrete NT (epi and norepi) into blood

eyes (iris):

1. radial muscle contracts = mydriasis = pupil dilates > more light in eye

2. ciliary muscle relaxes = distant vision = lens goes from biconcave to flat > more light into eye

heart: sympathetic cardiac nerve

1. SA node accelerates

2. increased force of muscle contraction

blood vessels:

1. skin and viscera > constrict

2. skeletal and cardiac muscle cells > dilate

-need more blood in the important organs for fight or flight > increase in BP

bronchiolar smooth muscle

1. muscles relax > airways open > more O2 gets in

GI tract

1. smooth muscle relaxes > GI motility decreases

2. sphincters contract > close

genitourinary smooth muscle:

1. bladder muscle relaxes

2. sphincters contract

metabolic functions of the liver:

1. glycogenolysis: breakdown of glycogen to glucose

2. gluconeogenesis: synthesis of glucose from non carbohydrate sources

adrenal medulla

1. stimulated to release epi

sweat glands

1. increase release of sweat

eyes:

1. sphincter contracts, pupils constricts = miosis

2. ciliary muscle contracts = accomodation or near vision > more biconvex

heart

1. SA node decelerates

2. DECREASE ATRIAL FORCE OF CONTRACTION > VENTRICLES NOT AFFECTED

bronchiolar smooth muscle

1. contracts

GI tract

1. smooth muscle contracts

2. sphincters open

3. gastric secretions increase

genitourinary smooth muscle

1. smooth muscle contracts > bladder

2. sphincters open

glands

1. lacrimal > increased tear secretion

2. parotid, submandibular, sublingual > increased salivary secretion

metabolic function of liver

1. increases glycogen synthesis: pancreas releases insulin so glucose can be uptaked into the cell > linked to a polysacc and turned into glycogen = energy store

SAME PREGANGLIONIC FIBER

postganglionic fiber releases norepi which binds to adrenergic receptors on the effector

stimulation of the adrenal cortex: adrenergic receptors bind to norepi > causes release of epi (hormone) 

proteins or glycoproteins

macromolecular complexes that serve as recognition sites (receptors) for NT and hormones

receptors for norepi = adrenoceptors

receptors for ach = cholinoceptors

receptors at all autonomic ganglia are neuronal nicotinic ach receptors

neuromuscular: also have muscle nicotinic ach receptors

receptors at neuro-effector junctions: PNS = muscarinic cholinoceptors, SNS = adrenoceptors

-ligand gated ion channel

-5 protein subunits that traverse the membrane > with a pore in the middle for ion movement

-rapid ion flux across cell membrane > causes depolarization

-very fast response: open and close in milliseconds

-glutamate and GABA receptors are also ligand gated ion channels

2 alpha (alpha1, alpha2)

3 beta (beta1, beta2, beta3)

based on

1. receptor location

2. signal transduction cascade

3. agonists and antagonists

beta1 receptor in the heart: GPCR that activates adenylate cyclase/cAMP system > cAMP activates PKA > phosphorylation kinase cascade > phosphorylates Ca channels > change shape and allows more Ca influx

5 muscarinic (M1 to M5)

based on

1. receptor location

2. signal transduction cascade

3. agonists and antagonists

muscarinic receptor on heart > bound to Ach > decreased adenylate cyclase activity because of Gi (inhibitory G protein) > decreased cAMP > increased K flux in atria/SA/AV node > decrease slow inward Ca channels > decrease If flux > slower AV/SA rate bradycardia, decreased force of contraction of atria

-400-500 AA residues

-7 transmembrane regions > 3rd cytoplasmic loop interacts with G protein

-G protein trimer: Ggamma, Gbeta, Galpha

-Galpha bound to GDP or GTP

-response lasts seconds

Gs: growth stimulation

Gi: inhibitory

Gq: found in the eye

1. adenylate cyclase/cAMP

2. phospholipase C/IP3/diacylglycerol 

3. guanylate cyclase/cGMP

PNS: increase in BP > carotid baroreceptors sends info via the glossopharyngeal nerve to the medulla oblongata > stimulates vagus nerve > release ach on the heart to slow down heart rate (SA and AV node) and atrial contraction 

SNS: sudden decrease in BP > carotid baroreceptors send info via glossopharyngeal nerve to the medulla oblongata > postganglionic fiber synapses with the chain ganglia > comes out as the sympathetic cardiac nerve > release norepi onto beta1 adrenergic receptor >innervates pacemakers and muscles > increase rate (SA and AV node) and force of contraction of the atria and ventricle

atropine

result: modest tachycardia

clinical use: give atropine IV for sinus bradycardia (myocardial infarction)

adrenaline

result: positive chronotropic and inotropic effects

clinical use:

1. adrenaline IV following cardiac arrest

2. dobutamine (beta1 adrenergic receptor selective) IV for cardiogenic shock

propanolol (non-selective)

result: reduced effect of exercise/excitement on HR and CO

clinical use: propanolol or atenolol (beta1 adrenergic receptor selective) for angina pectoris, post MI, dysrhythmias