Pain psychobiology/pharmacology Flashcards
passive, direct transmission system from peripheral receptors to the cortex
nociceptive pain
Examples of nociceptive pain
acute trauma, arthritis, and tumor invasion
Acute pain starts in
the periphery, is relayed to the spinal cord, and then passes up to the brain where it produces a negative reaction
Pain producing stimuli are detected by
specialized afferent neurons called nociceptors
free nerve endings that respond to a broad range of physical and chemical stimuli at intensities that can cause damage
nociceptors
Which pain fibers send the signal to the dorsal horn of the spinal cord by way of the dorsal root ganglion?
Aδ and C
Which pain fibers are myelinated axons that quickly send the first sharp signals of pain?
Aδ
Which unmyelinated pain fibers send a slower dull pain signal; major player in chronic pain?
C fibers
nociceptive afferent nerve fibbers synapse to neurons that cross to the contralateral side of the brain
Spinal cord dorsal horn
After crossing the dorsal horn, the ascending pain signal can be modified by
descending fibers or from simultaneous activity by non pain neurons
Dampen the pain Signal in the gate theory of pain
AB fibers
This type of pain allows the subject to become aware of the location of the pain and answer the question, where does it hurt? Signal travels up the spinothalamic tract, synapses in the lateral thalamus and proceeds to the somatosensory cortex
Sensory discriminative domain
Signals communicate the intensity of the sensation and answer the question, “how much does it hurt?”.
Affective-motivational domain
This explains the natural occurrence of depression, hyperfocus, and anxiety we see with patients in pain.
The affective-motivational domain end in the cerebral cortex
a term used to describe rare genetic conditions in which people lack the ability to sense pain.
Congenital Insensitivity to pain
No A-delta and C fibers
Frank Congenital Insensitivity to Pain
These people feel pain, but are not motivated to do anything about it. Normal peripheral nerves but have a central impairment of affective-motivational component
Congenital indifference to pain
This is an autosomal recessive disorder; inability to incorporate growth factor into nerve cells. Has no pain fibers.
Congenital Insensitivity to Pain with Anhidrosis
How is pain tolerance affected in those with schizophrenia?
Increased pain tolerance
Pain pathways are
Descending (top down control of pain)
kappa opioid receptor is thought to play a role in
pain and depressive symptoms
Activation of the kappa opioid receptor can provide some
analgesia
Antagonism of the kappa opioid receptor can provide
relief from some depressive symptoms associated with opioid withdrawal
The delta opioid receptor is thought to play a role
in modulating chronic pain and is activated by enkephalins
Antagonizing delta opioid receptors may play
an active role in pain relief
The Mu receptor’s activation is required for
most analgesics
The affinity that a medication has for the mu receptor correlates with
its potency as an analgesic
What binds with the mu receptor and acts as the quintessential antagonist for it, blocks activation, and can precipitate withdrawal
Naloxone
Which receptor is most closely associated with euphoria and abuse
mu
Evidence for long-term use of opioids for nonmalignant chronic pain is
almost nonexistent
Why is dose escalation a bad thing?
Tolerance to analgesic and euphoric effects develops quickly, which requires dose escalation. Tolerance for respiratory depression develops slower, which explains why dose escalation by well-meaning prescribers can precipitate an overdose
Long term use of opioids leading to increased sensitivity to painful stimuli is called
opioid hyperalgesia
This sensitivity is induced by morphine and is caused by an inflammatory response (cytokines) mediated by spinal microglia; possibly having acute pain transition into chronic pain.
Persistent pain sensitivity
Athletes, performing artists, soldiers wounded in battle some women in labor may have a stimulated opioid dependent pathway to inhibit pain or an endocannabinoid accumulation in the PAG. This is called.
Stress induced analgesia
This treatment causes a decrease awareness in pain perception brain areas associated with endogenous opioids. Increased activity involved with top down suppression of pain.
Placebos
Chronic neuropathic pain syndromes can be treated with psychiatric medications such as…
alpha-2-delta ligands and SNRIs
Pain that arises from damage to, or dysfunction of, any part of the peripheral or central nervous system
neuropathic pain
Pain that is caused by activation of nociceptive nerve fibers
Nociceptive pain
When plastic changes occur in the dorsal pain (such as phantom pain) it is called
segmental central sensitization
Hyperalgesia
exaggerated or prolonged response to any noxious input
When plastic changes occur in brain sites within the nociceptive pathway especially the thalamus and cortex (fibromyalgia, syndrome of chronic widespread pain, painful depression, anxiety disorders such as PTSD with pain)
Suprasegmental central sensitization (the brain learns from former pain and starts spontaneously activating its pain pathways)
SSRIs improve depression and
do not touch pain
SNRIs improve depression and
can treat neuropathy
Drugs that relieve pain without causing the loss of consciousness
Analgesics
A general term that is defined as any drug, natural or synthetic that has actions like those of morphine
Opioid agents
A term that applies only to compounds present in opoium
opiate
Drugs that act at opioid receptors can be
agonists, partial agonists, antagonists or, agonist/antagonists
Activate mu receptors and kappa receptors, produce analgesia euphoria, sedation, respiratory depression, physical dependence, constipation, and other effects…
pure opioid agonists
what are two examples of pure opioid agonists?
morphine and codeine
Higher dose-response curve, so same amount produces partial response. higher affinity for mu receptors than opioids, so will block them. Slower dissociation from mu receptors than opioids so styas around.
Partial agonist opioids
What is an example of a partial agonist opioid?
Buprenorphine (Subutex)
Blocks the post-syanptic receptors from binding with exogenous or endogenous agonist, thus preventing or reversing binding of the opioid agonist. Causes immediate reversal of respiratory and CNS depression of the opioid but also reerses any pain blocking.
Pure opioid antaginist
What are examples of pure opioid antagonists?
Naloxone and Methylnaltrexone (treats opioid induced constipation)
What are combination agents such as Buprenorphine/Naloxone (suboxone) used for?
medication assisted treatment (MAT) of opioid dependence
Morphine relieves pain by mimicking the actions of
endogenous opioid peptides, primarily at mu receptors
If morphine metabolites build up they cause
headaches
What is a population that morphine is contraindicated in?
compromised renal function or on dialysis
Adverse effects of morphine
respiratory depression, constipation, orthostatic hypotension, urinary retention and hesitancy, emesis, euphoria/dysphoria, sedation, neurotoxicity
What are the signs and symptoms of morphine withdrawal? how long does it last? how lethal is it?
yawning, rhinorrhea, sweating, violent sneezing, weakness, N/V/D, abdominal cramps, bone and muscle pain, muscle spasms, and kicking movements. 7-10 days without treatment. unpleasant but not lethal.
What is the classic triad of morphine toxicity?
coma, respiratory depression, pinpoint pupils
What is the relative potency of fentanyl?
100 times the potency of morphine
What is codeine’s action
10% converts to morphine in liver
What makes Buprenorphine such an effective choice in medication-assisted treatment for opioid dependence?
It is a mu-receptor partial agonist (main assistance in treating opioid dependence) but it also antagonizes kappa and delta subtypes which relieve some of the depressive symptoms associated with opioid withdrawal.
Define “use” in relationship to opioids
intake of substances that is consistent with health care needs and social norms
Define “abuse” in relationship to opioids
Intake of substances that is inconsistent with health care needs or social norms
Define “physical dependence” in relationship to opioids
State in which an abstinence syndrome will occur if the dependence producing drug is abruptly withdrawn. Not equated with addiction.
Define “addiction” in relationship to opioids
Behavior pattern characterized by continued use of a psychoactive substance despite physical, psychologic, or social harm.
What are the four pure opioid antagonists?
Naloxone (Narcan), Naltrexone (ReVia), Methylnaltrexone (Relistor), Alvimpoan (Entereg)
If Naloxone is given to an individual who is physically dependent on opioids it will…
precipitate an immediate withdrawal reaction
Naltrexone is contraindicated for patients with
acute hepatitis or liver failure
Alvimopan is especially useful for treating
the adverse effects of opioids on bowel function WITHOUT reducing the pain relieving effects of narcotics. Only available under a special program.
What does tramadol treat?
mild to severe pain (has a suicide risk). No respiratory depression, physical dependence or abuse.
What does Ziconotide (Prialt) treat?
pain management available only through intrathecal pump. Non-opioid.
What does Clonidine treat?
withdrawal symptoms. Not an opioid.
What does Dexmedetomidine (Precedex)?
Sedation or for overdose of amphetamines/cocaine. IV only.
Tramadol should not be combined with?
CNS depressants (cause fatal overdose)
What can happen if Tramadol is taken with an SSRI?
Tramadol also blocks the uptake of serotonin and can cause serotonin syndrome.
Adverse effects of Clonidine?
Cardiovascular: severe hypotension, rebound hypertension, and bradycardia
Ziconotide is an opioid antagonist at
voltage-sensitive calcium channels
This nonopioid centrally acting analgesic is typically used for intubation and mechanical ventilation or short-term surgical procedures
Dexmedetomidine
What are the three types of severe headaches?
migraine, cluster, tension
Cluster headaches the primary therapy is directed at…and the medications used are…
prophylaxis; glucocorticoids, verapamil, and lithium
Tension headaches are treated by
non-opioid analgesics and NSAIDS along with stress management
Migraine headaches are used both to prevent and abort migraines. What are two migraine specific drugs?
Sumatriptan, Ergotamine
What drugs are contraindicated when taking sumatriptan?
drugs that cause vasodilation
Adverse effects of sumatriptan include
chest symptoms, coronary vasospasm, teratogenesis, vertigo, malaise, fatigue, and tingling sensations…bad taste with intranasal form
Ergotamine can cause dependency and toxicity causes
Ergotism
What are the symptoms of ergotism?
painful seizures, spasms, diarrhea, paresthesias, itching, mania/psychosis, headaches, nausea, and vomiting. Dry gangrene.
