Neuro3: Clinical Pain And Drug Management

Front 1

IASP definition of pain

Back 1

Unpleasant sensory and emotional experience that is associated with actual or potential tissue damage that is described in therms of such damage

NO tissue damage actually required

Front 2

Prevalence of pain

Back 2

60-80% medical complaints, 1/3 get chronic pain in life

Front 3

Classifications of Pain, IDEAL and MOST USED

Back 3

Anatomic - where is it coming from

Etiologic - IDEAL APPROACH - what is causing pain

Qualitative - Burning vs sharp

Temporal - MOST USED - acute vs chronic

Front 4

Acute Pain overview

Back 4

Short-acting, disease process or event specific pain that would resolve even if no treatment due to healing

Not a treatment problem

Front 5

Chronic Pain overview

Back 5

Pain that persists longer than supposed to or recurrent. Pain often without precisely defined etiology

Treatment problem

Front 6

False "diagnoses" of chronic pain

Back 6

Anything just naming pain (ie. headache, neck pain, etc) or just saying pain related (shingles-related, stroke related etc.)

Just descriptive and doesn't tell real etiology

Front 7

Treatment-related chronic pain classification, and medical response

Back 7

Nociceptive - identifiable ongoing tissue damage

Responds to traditional analgesics (anti-inflammatories and opioids)

Neuropathic - some injury to nervous system itself and still echoes

Responds to "adjuvant" analgesics to help with nerve pain

Mixed - BOTH from ex a traumatic injury affecting both

Front 8

Nociceptive Pain fibers, definition

Back 8

Associated with actual or potential tissue damage of non-neural structures with a DEFINABLE pathology (but symptoms may be out of proportion)

C and Alpha, delta nerve fibers activated by thermal, chemical and mechanical stimuli

Front 9

Signs/Symptoms of Tissue Damage/Inflammation

Back 9

Redness

Swelling

Pain (localized)

Warmth

May be "hidden" (deep in joint structure or viscera)

Front 10

Effects of nociceptive pain

Back 10

increased catecholamines - BP and HR
increased cortisol and other metabolic responses (stress response)
respiratory effects: hold breath at first then breath faster
autonomic effects: sweating
Physiologic effects: aversion and stress requirements for pain (it has to bother you otherwise not pain by definition)

Front 11

Neuropathic pain definition, timeframe, presentation

Back 11

Due to injury of neural structures anywhere along "pain pathway"

May be immediate or delayed. Bizarre or emotional appearance

Pain appears way out of the proportion to the pathology since no defined local pathology

Front 12

Reliable vs nonreliable effects of Neuropathic Pain

Back 12

Unreliable

May or may not have increased catecholamines

May or may not have decreased cortisol

Unreliable respiratory effects and autonomic effects

PHYSIOLOGIC EFFECTS ARE RELIEABLE - emotional distress and stress

Front 13

Clinical Manifestations of Neuropathic Pain

Back 13

Allodynia - innocuous stuff causing pain

Hyperalgesia - pain out of proportion

May have: autonomic dysfunction, trophic changes, motor impairment, sings of neural dysfunction

USUALLY series of peaks and valleys of pain, cyclic without patient control

Often LACKS signs of nociceptive pain etiologies: No redness, swelling, etc.

Spontaneous pain, often with profound psychological responses. Can have evidence of nerve damage

Front 14

Neuropathic pain types

Back 14

Compressive

Inflammatory

Deafferentation

Central injury

SNS related

Front 15

History clues suggestive for potential neuropathic pain

Back 15

Etiologic factors: DIABETES, alcohol, heavy metals, vitamin deficient, SHINGLES, hereditary factors, TRAUMA, CHEMOTHERAPY (via axonal propagation) - all can cause nerve injury

Spontaneous nature to the pain

Atypical stimuli relationship - not just if poke it hurts but without obvious cause

Activity-related onset (repetitive motion, disc herniation, carpal tunnel, etc)

Front 16

Evidence of nerve injury

Back 16

Physical exam shows neurologic deficit; hyperalgesia, allodynia; altered motor function or bulk

Altered functional testing - ex. abnormal micturition test

Imaging - MRI

Abnormal functional neurophysiologic studies (nerve conduction, EMG, sympathetic function (GSR))

Front 17

Brain studies for neuropathic pain

Back 17

Can use radiotracers when pain and pain free. Bloodflow often localizes to region of neuropathic pain

i.e pt with SCI and no feeling below hip but feels pain in foot, foot sensation area may light up

Front 18

Examples of Mixed type pain

Back 18

Not clearly nociceptive (post op, mechanical low back pain, sports injury, etc) but not clearly neuropathic (CRPS, trigeminal neuralgia, central post stroke pain, distal polyneuropathy from diabetes or HIV)

Include sickle cell, arthritis, postherpetic neuralgia and neuropathic low back bain

Try to find which it looks like most to treat

Front 19

Potential causes of neuropathic pain

Back 19

Very heterogeneous, same nerve damage can cause different phenotypes due to genotypes, sprouting, misconneciton, increased exchitability of what remains or disinhibition

May be related to supraspinal, segmental and glial influences (cytokines to change dorsal horn neurons leading to allodynia and hyperalgesia)

Front 20

Acute Pain Treatment goal, Pharmacology

Back 20

Assume nociceptive if acute, traditional analgesics and time are best along with resolution/treatment of etiology

Pharmacology - traditional analgecs including opiods, NSAIDs/COX 2 inh., Corticosteroids, adjuvants

Front 21

Chronic Pain treatment goal

Back 21

Move along a continuum of least to most invasive

Psychological/physical approaches to topical medications to oral medications to injections to interventional techniques

Front 22

Opiates vs Opioids, MOA, use

Back 22

Morphine, heroin, hydrocodone, oxycodone

Treat nociceptive pain

Alkaloids from natural compounds

Opiate - exogenous
Opioid - endogenous (enkephalins)

MOA: most are mu opioid receptor agonists and have identical efficacy

Isolated kappa agonists are mixed agonists and less efficacious

Front 23

Cyclo-oxygenase inhibitors MOA, types, specific vs nonspecific

Back 23

traditional analgesics, steroidal and nonsteroidal classes

Cox inhibitors are most common - inhibit prostaglandin synthesis (swelling, redness, inflammation)

Cox1 - constitutive, related to GI system, helps kidney blood flow

Cox2 - inducible from tissue damage

Nonspecific - ibuprofen, naproxen - limited b/c can get renal, GI, immune system failure

Specific COX2 in theory best

Front 24

Corticosteroids, types, use

Back 24

Steroids made in adrenal cortex

Types: Glucocorticoids, Mineralocorticoids

Each has specific receptor and physiological effects with crossover, mild interaction with gonadal hormones

Front 25

Glucocorticoids Role, MOA, formulations, comparative potencies

Back 25

Corticosterone, Cortisone, Cortisol

Role: control carb, fat and protein metabolism, ANTI-INFLAMMATORY (block phospholipid release)

MOA: bind glucocorticoid receptor - ligand activated TF present in most cells of body in cytoplasm. When glucocorticoid enters and binds heat-shock proteins released. BLOCKS NFkB or AP1 linked cytokine responses (inflammation cascade) and transcribes heat shock antiinflammatory genes

Formulations: oral, topical,

prenteral forms (anesthesia and pain)
Non-particulate (soluble) - dexamethasone, betamethasone, hydrocortisone, solu-medrol
Particulate (depot forms) - colloid lipid droplets (depoMedrol), colloid-crystals (celestone-betamethasone)

Potencies - Hydrocortisone and cortisone affect gluco and mineralo-corticoid receptors equally. Dexa and betamethasone selective for gluco

Front 26

Selectivity both glucocorticoid vs mineralocorticoid receptor

Back 26

Hydrocortisone, cortisone - equal to both

dexamethasone, beta methasone - selective for glucocorticoid receptors

Aldosterone is just mineralocorticoid

Front 27

Depot vs nondepot forms of glucocorticoid significance

Back 27

Depot forms have LONG half life - colloid lipid droplets (depoMedrol), colloid-crystals (celestone-betamethasone)

Front 28

Toxicities of glucocorticoids

Back 28

Teratogenic (1st trimester) so DONT" GIVE to people trying to get pregnant or may be pregnant

Cushing's Disease (hyperadrenalism) - when given too much leads to delayed wound healing, inh. of bone formation, glucose intolerance, fat increase, infection risk, CNS euphoria, depression, mania, muscle weakness and wasting from negative nitrogen balance (UP BUN)

Addison's Disease (hypoadrenalism) - may be caused by giving exogenous corticoids

Front 29

Common ADJUVANT neuropathic pain medication modalities

Back 29

Antidepressants, anticonvulsants, antiarrhythmics, antispastics, alpha adrenergic agents, topicals and other

GOAL is to lower peaks and keep far apart,

discovered serendipitously

Front 30

Antidepressants used for neuropathic pain

Back 30

NOT all effective for pain

Classic-tricyclic antidepressants
SSRIs - less effect
SNRIs - GOOD (duloxetine, minalcipran)


Help if pain from depression

Front 31

First line treatment for neuropathic pain

Back 31

Anticonvulsants - GABAPENTIN

Front 32

Neurontin and Lyrica MOA, use, why are they used, ASE

Back 32

Anticonvulsants

Lyrica = pregabalin and neurontin = gabapentin. Both treat NEUROPATHIC PAIN

Act on calcium channel

Clean drug, no protein binding, no enzyme induction, calcium channel effects (not GABA), renal excretion

Potency differencies and CNS penetration due to lipid solubility

Lyrica FDA for fibromyalgia

USE: almost any neuropathic pain from any cause.

ASE: somnolence, dizziness (fall risk), nystagmus, ataxia, tremors, fatigue,

Front 33

Anti-arrythmics MOA, use

Back 33

Mexilitine, Lamotrigine, Carbamazepine

Neuropathic pain agents

MOA: sodium channel blocking effects

Use: IV local anesthetics

Front 34

Antispastic agents and alpha 2 agents, use, MOA, ASE

Back 34

Tizanidine, Clonidine, Baclofen

USE: SPASMS PRESENT WITH PAIN

MOA: decrease muscle tone by working at a motor level or brainstem level. Decrease

ASE: CV (orthostatic hypotension), CNS (ataxia, sedation, memory), ANS, Hepatotoxicity, renal tox, GI tox, depression

Front 35

Tizanidine vs Clonodine, vs Baclofen

Back 35

All are antispasmatic agents for neuropathic pain

Tizandine (alpha 2 agonist) - sedation > hypotension

Clonidine (alpha 2 agonist) - sedation < hypotension

Baclofen (GABA-B agonist)

Front 36

Other treatment modalities (non drugs) for pain

Back 36

Injection therapy - blocks of steroids into specific areas

Counterstimulus therapies (TENS, SCS)

Psychological therapies

Physical therapies