Pain Pathway

Mu 1

- predominantly supra spinal analgesia -some spinal analgesia -DECREASED HR -EUPHORIA lower abuse potential urinary retention PURITUS

Mu 2

-SPINAL ANALGESIA only -RESP depression -PHYSICAL DEPENDENCE (addiction) -constipation Remi appears to lack delta and kappa agonist activity

Opioid Agonist-Antagonist

-can be used to reverse respiratory depression (either antagonists or partial agonists for mu receptor) effectively displacing opioid agonist from mu 2 receptor however some degree or spinal and supra spinal analgesia would be maintained because they stimulate kappa and delta receptors

Pathway for slow-chronic pain

C2-3-P-O (from star wars?) C fibers: unmyelinated nerve endings that transmit diffuse slow, second burning, aching, throbbing pain --The C fibers terminate primarily in: *Rexed's Lamina II (SUBSTANCIA GELATINOSA) *Rexed's Lamina III C fibers impulse to lamina V from II and III and then immediately cross over to the contralateral spinothalamic tract and ascend to the brain ** The major NT released from C fibers is Substance P, which binds to NK-1 (neurokinin 1) receptors on the post synaptic membrane

Clavicle

C4

Lipophilic Opioids

LIPID LOVING Easily pass through lipid bilayers Quick onset, duration short early onset analgesia Intrathecal: diffusion out of CSF is rapid d/t lipophilic properties, less rostral spread, more systemic absorption that leads to early resp depression/ late depression of ventilation does not occur Epidural: very minimal rostral spread within CSF, bathes the spinal cord but also increased systemic absorption due to easy lipid bilayer crossing

Hydrophillic Opioids

MORPHINE IS HYDROPHILIC *water loving/ do not cross lipid bilayer easily *slow onset, longer duration Intrathecal: less vascular--> diffuses out of subarachnoid space SLOWLY, onset slow, duration prolonged... LATE DEPRESSION OF RESPIRATION ONLY (early depression does not occur because uptake initially by systemic circulation is minimal) ROSTRAL (CEPHALAD, HEADWARD, NORTH) spread occurs and contributes to late depression of ventilation (6-12 hours later circulates to brainstem)--> much greater quantities of hydrophilic drugs spread rostral because they are more trapped that lipophilic drugs Epidural: onset slow, duration prolonged BUT epidural greater systemic uptake d/t increased vascularity can contribute to early resp depression (within 2 hours): although rare --still contributes to late vent depression because morphine absorbs within CSF--> rostral spread to brainstem

Competitive Opioid Antagonists

Naloxone (Narcan) Naltrexon (oipiod and alcohol addition; long action) Nalmefene all opioid receptor subtypes are blocked by the competitive antagonists SE Narcan: -reveral of analgesia -excitement/dysphoria -tachycardia -htn -cardiac dysrhythmia -pulmonary edema *increase in sympathetic nervous system activity

Dorsal Root Ganglion

The cell bodies of A delta and C afferent fibers are found in the dorsal root ganglion and pass through the tract of Lissauer (ascend or descend)

Substancia Gelatinosa

The first neurons in the slow chronic pain pathway (C fiber) synapses with the interneurons in the substancia gelatinosa (RL II, III) of the spinal cord and releases the excitatory transmitter substance P to these interneurons Enkephaline releasing interneurons also synapse in the substance P releasing terminal When enkephalin is release and binds to the mu 2 receptor on the pre synaptic C fiber neuron, the release of substance P is decreased and the amount of action potential to the brain is decreased, decreasing the perception of pain **In the same way neuraxial opioids bind at presynaptic mu 2 receptors and decrease the release of substance P in the substantial gelatinosa (spinal opioid analgesia is mediated primarily by mu 2 receptors)

Dorsolateral Funiculus

descending tract modulates pain

Supraspinal analgesia

occur when opioids act in the brain at sites including the limbic system, hypothalamus, and thalamus mediated by mu1, kappa, delta receptors (mu 1 = dominant) Its response to pain is altered

Spinal Analgesia

occurs when transmission of pain impulses through the substantial gelatinous (Rexed's lamina II) is supressed All pain receptors mediate spinal analgesia but mu 2 is the dominant receptor Fewer action potential are relayed to the brain when spinal analgesia occurs Results from action of opioids in the substancia gelatinous (after epidural or intrathecal administration) oe in the periventricular/periaqueductal gray (after IV administration) **Pts perception of pain diminished

Neuraxial opioids side effects

pruritus neonatal morbidity nausea sexual dysfunction urinary retention ocular dysfunction depression of ventilation GI dysfunction Sedation thermoregulatory dysfunction CNS sedation water retention

Homunculus

relative distribution of body parts in the somatosensory cortex Man named HAL hanging upside down from the longitudinal tissue: Head, arms, legs There is no representation of the genitalia on the homunculus because pain and temp from the genitalia are mediated by the autonomic system

Kappa

spinal and supra spinal analgesia DYSPHORIA (hallucinations) Sedation

Pathway for fast sharp pain

A delta: myelinated nerve endings, transmit well localized first pain or fast pain (sharp, stinging, prickling) After leaving the tract of Lissauer. the axons of the A delta fibers enter the dorsal horn and terminate in: *Rexed's Lamina I *Rexed's Lamina V *Second order neurons leaving lamina I and V cross to the CONTRALATERAL LATERAL SPINOTHALAMIC TRACT and ascend to the brain **The major neurotrasmitter release from A delta fibers is glutamate which binds to AMPA and NMDA

Anterolateral System

Ascending sensory spinal cord tract carrying pain and temperature is the lateral spinaothalamic tract which is a component of the Anterolateral System

Modulation of Pain by descending spinal cord tracts

Impulses arising in the periventricular/ periaquaductal gray matter of the brainstem are transmitted through the nucleus raphe magnus to the substancia gelatinosa by way of the descending dorsolateral funiculus Action potentials arriving at the substancia gelatinous activate enkephalin neurons which decreases the release of substance P, thereby reducing the number of pain impulses ascending in the later spinothalamic tract in addition, action potentials descending in the dorsolateral funiculus hyperpolarize cell bodies of the second neurons in the pain pathway, thereby also decreasing the number of action potentials in the ascending lateral spinalamic tract The descending dorsolateral tract modulates pain Intravenous opioids produce analgesia in part by initiating action potentials in the descending dorsolateral funiculus and work by decreasing nerve impulses passing through the substancia gelatinosa

Tibia

L4-L5

Perineum

S2-S5

Xiphoid

T 6

Umbilicus

T10

Nipples

T4