Pain

Question 1

difference between opiates and opioids

Answer 1

opiates: derivatives of poppy plants (heroin, morphine)
opioids: any drug that occupies opioid receptors (fentanyl, methadone)

Question 2

explain endogenous Mu opioid synthesis

Answer 2

Beta-endorphin comes from beta-lipotropin, which comes from POMC

Question 3

what are the most important opioid receptors for pain relief?

Answer 3

Mu receptors

-spread throughout CNS and gut and WBC

Question 4

explain the mechanism of endorphin activity in the CNS?

Answer 4

involved at inhibiting GABA (decrease) and thus disinhibiting dopamine (increase)
-receptors in descending pain circuit (amygdala, mesencephalic reticular formation, PAG, rostral ventral medulla)

Question 5

explain the mechanism of endorphin activity in the PNS?

Answer 5

primary afferent neurons, peripheral sensory nerve fibers, dorsal root ganglia
-inhibition of substance P and other tachykinin release

Question 6

what are the proposed mechanisms of endorphin release?

Answer 6

2 systems in place: central and peripheral

• peripheral: mediated by stress and ACTH co-release
• -corticotrophs in anterior pituitary synthesize ACTH and beta-endorphin in equimolar amounts
• central: innervation of hypothalamus, midbrain, and rostral medulla
• -cell bodies of opioidergic neurons in median eminence of hypothalamus

Question 7

what are endorphins co-released with? during what? what are release mediators?

Answer 7

ACTH during stress reactions from anterior pituitary

• RM: 5-HETE, LTA4, LTB4, and other lipoxygenase products; angiotensin II, 5-HT
• -evidence of beta-endorphins in T and B lymphocytes, monocytes, and MP during inflammatory reactions
• process involves activation of cAMP by beta-adrenoreceptor activation

Question 8

what is the AAAP (American Academy of Addiction Society) policy for opioids in chronic non-malignant pain?

Answer 8

Rx for more than 1 month should trigger more complex thinking

• full physical; is pain unusual
• high dose opiates generally not helpful
• hyperalgesia is reduced when off opiates, risk of misuse, death, sharing, selling
• ongoing risk assessments

Question 9

what do prostaglandins do for the stomach and what happens when COX-2 specific inhibitors are used?

Answer 9

PGEs protect the stomach lining from acid

-COX-2 specific inhibitors like celecoxib and low dose meloxicam cause less gastric irritation than other COX inhibitors

Question 10

what causes fever?

Answer 10

prostaglandin E2; signals hypothalamus to increase body’s thermal set point

Question 11

how do prostaglandins cause vasodilation?

Answer 11

reversible decrease in renal blood flow

Question 12

what is the only NSAID that causes irreversible inhibition of COX and what is it used for?

Answer 12

aspirin

-prevents coronary artery occlusion and colorectal cancer

Question 13

NSAIDs versus opioids

Answer 13

• neuropathic pain should be addressed via neural function: anticonvulsants, tricyclics
• NSAIDs address cause of inflammatory pain, such as post-tramatic, post-surgical
• opioids make patient less concerned about the pain

Question 14

how do all antiepileptic drugs function?

Answer 14

lowering a neuron’s ability to fire by hyperpolarization and disallowing depolarization

Question 15

what are anti-epileptic drugs used to treat other than epilepsy? why?

Answer 15

• bipolar disorder
• anxiety disorder
• substance withdrawal
• migraines
• fibromyalgia
• diabetic neuropathy

these all involve neuronal excessive firing rates as their final pathway

Question 16

what are the pain nerve fibers? how are they activated?

Answer 16

A-beta-fiber: non-noxious mechanical stimuli
A-delta-fiber: noxious mechanical stimuli
C-fiber: noxious heat and chemical stimuli

activated by injury and AP occur via Na+ and/or Ca++ channel activation, influx, and depolarization

Question 17

what are the “three pain bus stops”?

Answer 17

1. spinal reflex
2. thalamus/limbic semiconscious
3. cortex conscious

Question 18

how does neuropathic pain come about? steps?

Answer 18

when inflammatory pain goes awry

1. subthreshold pain response (no pain, only annoying) shows small Ca++ influx
2. full pain response (acute) shows significant Ca++ and Na+ influx
3. system goes awry, gets stuck, and circuits get glued together (central sensitization and excessive/chronic pain response that is segmental or supra-segmental)
   - neuropathic pain from Na+, Ca++ influx, and now glutamate release

Question 19

what does increased glutamate release represent?

Answer 19

long-term potentiation of pain

Question 20

how can you relieve painful excessive nociceptive activity?

Answer 20

central sensitization

• Ca++ channel blocker (gabapentin)
• Na+ channel blocker (carbamazepine)
• glutamate blocker (lamotrigine, actually Na CB)

Question 21

what are general side-effects of AEDs?

Answer 21

generally cause sedation, psychomotor/cognitive impairment, ataxia, tremor

Question 22

use and side effects of Carbamazepine?

Answer 22

for trigeminal neuralgia

-ASE: aplastic anemia (requires blood levels), p450 3A4 inducer causing drug interactions

Question 23

use and side effects of Lamotrigine?

Answer 23

no FDA approvals for pain, but used off-label as AED to block glutamate
-causes Stevens-Johnson syndrome rash

Question 24

use and side effects of Gabapentin?

Answer 24

for diabetic neuropathy

-ASE: weight gain, sedation

Question 25

use and side effects of pregabalin?

Answer 25

for diabetic neuropathy, fibromyalgia

-mild addiction, weight gain, sedation

Question 26

use and side effects of topiramate?

Answer 26

for migraines

-weight loss, acidosis, oligohydrosis, glaucoma

Question 27

what do antidepressants treat outside of depression?

Answer 27

• anxiety disorders
• fibromyalgia
• neuropathic pain
• vasomotor symptoms of menopause
• premenstrual disorders
• urinary incontenence

Question 28

what is the role of NE and antidepressants?

Answer 28

1. ascending NE projections, if strong, may remit depression, anxiety, and ADHD
   - descending NE projections, if weak, cause pain
2. antidepressant with NRI will strengthen ascending pathway and psychiatric symptoms may resolve
3. antidepressant with NRI will strengthen descending pathway (SRI has less role) and impinges upon GABA interneuron system that dampens ability of ascending pain fibers to fire and pain symptoms may resolve

Question 29

side effects of duloxetine and milnacipran?

Answer 29

SNRIs

• serotonin: headache, Gi distress, insomnia, fatigue, sexual, weight gain
• NE: nausea, dry mouth, HTN, appetite suppression

Question 30

side effects of amitryptiline?

Answer 30

TCA

• serotonin: headache, Gi distress, insomnia, fatigue, sexual, weight gain
• NE: nausea, dry mouth, HTN, appetite suppression
• anticholinergic: dry mouth, constipation, blurred vision

Question 31

reflexive VS conscious pain?

Answer 31

reflexive: occurs at level of spinal cord, maybe thalamus (unconscious)
(semi) conscious pain occurs at level of limbic system and cortex (amygdala)

Question 32

what is transference and countertransference?

Answer 32

transference: patients are assuming you won’t help or listen; they will be short and rude
countertransference: you will likely be stressed, irritated, short, and rude as these patients don’t follow medical rules