Pain Pathway and Opioids Flashcards
What fibers are responsible for the transmission of “first pain” or “fast pain”?
A-delta; free (naked) nerve endings, myelinated, diameter 1-4, well-localized discriminative sensation (sharp, stinging, pricking), duration of pain coincides with during of painful stimulus
What fibers are responsible for “second pain” or “slow pain”?
C fibers; free (naked) nerve endings, unmyelinated, diameter 0.4-1.2, diffuse and persistent burning, aching, throbbing–> duration of pain exceeds duration of stimulus
What are the fibers involved in peripheral pain stimulus and the path to the spinal cord?
fast and slow pathways are activated in the periphery when free nerve endings of a-delta and c fiber are stimulated (DAMAGED); cell bodies of a-delta and c fiber afferents are located in the dorsal root ganglion–> A-delta and c fibers enter the dorsal cord, divide and ascend OR descend 1-3 segments in the tract of Lissauer
After leaving the tract of Lissauer, what is the transmission pathway for fast-sharp pain?
after leaving the tract of Lissauer, the axons of the a-delta fibers enter the dorsal horn and terminate in Rexed’s lamina I and lamina V–> second order neurons leaving lamina I or lamina V cross the contralateral spinothalamic tract and ascend to the brain
After leaving the tract of Lissauer, what is the transmission pathway for slow-chronic pain?
The C-fibers terminate primarily in lamina II and also lamina III–> interneurons transmit C-fiber impulses to lamina V from lamina II and III–> neurons leaving lamina V cross immediately to the contralateral lateral spinothalamic tract and ascend to the brain
What lamina is referred to as the substantia gelatinosa?
definitely lamina II, however some sources say it is II and III
What is the major neurotransmitter released from A-Delta fibers and where does it bind?
glutamate, which binds to AMPA receptors on the postsynaptic membrane
What is the major neurotransmitter released from C fibers and where does it bind?
substance P, which binds to the NK-1 receptors on the postsynaptic membrane
What is a descending tract that modulates pain?
dorsolateral fasciculus
What sensations are blocked in the lateral columns by epidural or spinal anesthesia?
bilateral loss of PAIN and TEMP
All sensory input except smell passes through the _____.
thalamus
What dermatome is around the level of the clavicle?
C4
What dermatome is around the level of the nipples?
T4
What dermatome is around the level of the umbilicus?
T10
What dermatome is around the level of the tibia?
L4-L5
What dermatome is around the level of the perineum?
S2-S5
What dermatome is around the level of the Xiphoid?
T6
Of the cervical nerves, which is motor only?
C1
Opioids stimulate the same receptors that are stimulated by the body’s own ________ and _________.
endorphins and enkephalins
How does neuraxial anesthesia work… in short?
after an opioid is injected into the intrathecal or epidural space, it diffuses into the substantia gelatinosa (rexed’s lamina II) and united with opioid receptors on the nerve terminal of the primary pain afferent; the release of substance P is reduced, and hence the transmission of impulses through the substantia gelatinosa is inhibited
What receptors mediate spinal analgesia? Which is primary?
Mu 1, Mu 2, kappa, delta….. primarily by Mu-2
Is morphine hydrophilic or phobic?
hydrophilic… slowly diffuses out CSF
Is fentanyl hydrophilic or hydrophobic?
hydrophobic…because it is lipophilic; diffusion out of CSF is rapid
What neurons get activated when action potentials arrive at the substantia gelatinosa?
enkephalins
What effect does the release of enkephalins have?
decreases the release of substance P…. thereby reducing the number of pain impulses ascending in the lateral spinothalamic tract
Most of the currently used opioid agonists are highly specific for ______ receptors.
Mu
While spinal analgesia is mediated by all opioid receptors, it is primarily mediated by _____ receptors.
Mu-2
Supraspinal analgesia is mediated by ALL receptors EXCEPT _______ receptors.
Mu-2
Supraspinal analgesia is mediated PRIMARILY by ______ receptors.
Mu-1
What are 3 of the primary side effects of Mu-1 receptors?
bradycardia, euphoria, pruritus
What are 3 of the primary side effects of Mu-2 receptors?
respiratory depression, addiction, and constipation
What are 2 of the primary side effects of kappa receptors?
sedation and dysphoria (hallucinations)
What receptors are responsible for the mediation of miosis and nausea/vomiting?
They have not yet been identified; BARASH
Remifentanil is a ______ (duration?) acting opioid, is metabolized by ______________________; it is a potent _____ receptors agonist and appears to lack ________ and _______ receptor agonist activity.
ultra short acting; non-specific plasma esterases; potent mu receptor agonist; appears to lack delta and kappa activity
What drug has received attention because of its role in the treatment of opioid and alcohol addiction?
long acting oral Naltrexone (Trexate)
Competitive opioid antagonists such as Naloxone (Narcan), Naltrexone (Trexate) and Nalmefene block _____ opioid receptors subtypes.
ALL
What are some common side effects of Naloxone (Narcan)?
reversal of analgesia, excitement/dysphoria, tachycardia, HTN, cardiac dysrhythmias, pulmonary edema; The side effects are a reflection of an increase in sympathetic nervous system activity–> sudden perception of pain
How do opioid agonist/antagonists work? What is the benefit of using them?
They are either antagonists or partial agonists for mu receptors (but they are not strongly activated so respiratory depression is unlikely) and kappa and delta receptors.
They maintain analgesia WITHOUT producing severe respiratory depression because they have little agonist effect on mu receptors; they mediate their clinical effects via kappa and delta receptors.
What are some commonly used opioid agonist/antagonist medications used?
Butorphanol (Stadol), Nalbuphine (Nubain), Nalorphine (Nalline), Dezocine (Dalgan), Buprenorphine (Buprenex), Pentazocine (Talwin)
Can an opioid agonist/antagonist be used to reverse opioid induced respiratory depression?
YES; they competitively inhibit mu receptors causing displacement of opioid agonist from mu-2 receptors.
What is the advantage of using an opioid agonist/antagonist to reverse respiratory depression?
because some degree of spinal analgesia and supraspinal analgesia would be maintained because opioid agonist/antagonist stimulate kappa and delta receptors
