Neuropathic Pain Flashcards
PDN
Painful diabetic neuropathy
• Prevalence.
– 10-20% of diabetics.
• 40-50% in pt w/ diabetic peripheral neuropathy (DPN).
• > In type II than type I??
• If neuropathy presenting symptom, ~50% dx with IGT or DM.
– Sumner et. al. Neurology 2003;60:108–11.
• UPDATE with Vit B12 deficiency as a cause.
Skim Patho (not holding us accountable in depth):
• Damage to peripheral nerves.
– hyperexcitability.
– Spontaneous impulses within axon & dorsal root ganglion of these peripheral nerves.
• Abnormal electrical connections.
• Coupling of sympathetic and afferent neurons and abnormal release of substance P from A fibers.
• Persistent nerve stimulation activates N- methyl d-aspartate (NMDA) receptors located postsynaptically in the dorsal horn
PHN definition and patho
Post-herpetic neuralgia
Reactivation of Varicella-Zoster virus
– Shingles.
• Incidence ~30%, up to 50% in those living to 85. • All ages - 1.2 - 4.8 cases/1000 persons/year.
– >60 years - 7.2 - 11.8 cases/1000/year.
• Distribution along dermatomes.
• Often causes PHN d/t sensory nerve damage.
– Reduced neurite densities
LBP
Low back pain
5th most common office visit reason.
– ~25% of adults – 1 day of LBP in past 3 months
– Most resolve in 1 month
• 1/3 moderate pain at 1 year
• 1 in 5 report substantial limitations
– $26.3 billion in 1998
• Acute vs. Chronic, +/- neuropathic
• Lumbosacral radiculopathy.
– Most common.
– Medication mismanagement.
NSAIDs and Smooth Muscle Relaxants should be used for acute LBP along with nonpharm
For chronic LBP: “…pharmacologic treatment with nonsteroidal anti-inflammatory drugs as first-line therapy, or tramadol or duloxetine as second-line therapy. Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweich the risks for individual patients and after a discussion of known risks and realistic benefits with patients.”
Mechanisms of nociceptive pain
- Stimulation
- Transmission
- Perception
- Modulation (body’s own way of shutting down pain pathway)
Modulation
Endogenous analgesic mechanisms
– Endogenous opiate system (enkephlins, dynorphins, beta-endorphins) mu, delta, and kappa receptors
– NMDA receptors decrease effects of opioids
NE & 5-HT neurons appear to provide:
– major descending modulation
– inhibition for transmission of nociceptive information to the rostral levels of the CNS
Neuropathy & Neuropathic Pain Definition/Description
Neuropathy: “A disturbance of function or pathological change in a nerve”
-happens because of nerve damage
• Neuropathic pain – “Pain caused by a lesion or disease of the somatosensory nervous system.”
• Neuropathic pain is a clinical description (and not a diagnosis) which requires a demonstrable lesion or a disease that satisfies established neurological diagnostic criteria.
Nervous System Damage
• Increased nerve cell firing
• Decreased inhibition of neuronal activity in central structures and/or
• Intact circuitry at the central level but a gain in response (sensitization) such that normal sensory input is amplified and sustained
Presentation / Assessment of Neuropathic Pain
• Spontaneous transmission
– Continuous
• Burning, throbbing, aching, shooting
– Intermittent (episodic, paroxysmal)
• Shooting, stabbing, or electric shock-like
• Hyperalgesia
– Increased pain from a stimulus that normally provokes pain.
• Allodynia
– Pain due to a stimulus that does not normally provoke pain.
Tricyclic Antidepressants (TCAs)
• Secondary (nortriptyline, desipramine)
• Tertiary (amitriptyline, imipramine)
Advantages
– Most data (oldest agents)
– Once daily dosing
– Concomitant insomnia, depression.
Disadvantages
– Delayed onset
– Anti-ach = Anticholinergic, BEERS criteria to avoid in older adults
- Cardiotoxic
Dosing
– 25mg hs, max 150mg/day.
– Trial – at least 6-8 weeks, 2 weeks @ max
Serotonin/Norepinephrine Reuptake Inhibitor
Duloxetine & Venlafaxine
Advantages
– Duloxetine FDA approved in PDN, fibromyalgia, and LBP
– Concomitant depression
– Side effect profile
Disadvantages
– Risk of serotonin syndrome +/- interacting meds
– Duloxetine contraindicated in
• Hepatic impairment
• Severe/end stage renal disease (<30ml/min)
Dosing
– Duloxetine – 30mg 1X/day, max 60mg 2X/day
– Venlafaxine – 37.5 1-2X/day, max 225mg/day
Milnacipran
Savella
FDA approved for only fibromyalgia
Doesn’t eliminate pain; response varies by pt (37% of subjects report ~50% reduction in pain)
MOA
– SNRI – 3:1 NE:5HT
– NMDA receptor binding
– Lacks histaminic and muscarinic activity
Advantages
– Well tolerated, can improve fatigue and decreased energy from fibromyalgia
Disadvantages
– Twice daily dosing
– HTN (because increase activity of NE)
Dosing
– Start 12.5 daily, titrate over 1 week to 50mg b.i.d.
– Max 100mg b.i.d.
alpha2-delta ligands (Gabapentinoids) MOA, adv., disadv.
Gabapentin
MOA: Modulates hyperexcited neurons
– binds to presynaptic neurons at the alpha2- delta (α 2-δ) subunit of voltage-gated calcium channels
– Drug binding reduces calcium influx into presynaptic terminals
– Decreased calcium influx reduces excessive release of excitatory neurotransmitters
Advantages
– Low incidence on DIs and ADRs
– FDA approved PHN
Disadvantages
– Mild CNS depression, significant in toxicity.
– Renal insufficiency.
• CrCl >= 60 ml/min: No dose adjustment needed.
• CrCl > 30—59 ml/min: Total dose range 400—1400 mg/day PO in 2 evenly divided doses.
• CrCl > 15—29 ml/min: Total dose range 200—700 mg/day PO given in one daily dose.
• CrCl = 15 ml/min: Total dose range 100—300 mg/day PO given in one daily dose as 100, 125, 150, 200, or 300 mg.
• CrCl < 15 ml/min: Reduce daily dose in proportion to CrCl (e.g., CrCl = 7.5 ml/min should receive one-half the dose that patients with CrCl of 15 ml/min receive).
alpha2-delta ligands (Gabapentinoids) Products and Dosing (skim this card)
Gabapentin Oral capsule, tablet and solution
• 300mg 3X/day start.
– Lower in renal impairment – 100mg 2-3X/day.
– Titrate every 3 days if tolerated.
– Max 3600mg/day.
– Variable onset of effect.
Gabapentin Oral tablet, extended release (GRALISE 300mg Tablet)
• Once daily, evening meal
• Titrate to 1800mg/day
Gabapentin enacarbil Oral tablet, extended release (Horizant 600mg)
• Twice daily X3 days, then 2 tabs twice daily
• Max 1200mg/day
Pregabalin
Advantages.
– Low incidence on DIs and ADRs.
– Concomitant anxiety.
– FDA indicated in PDN, PHN & fibromyalgia
Disadvantages.
– DEA schedule V – dependency, euphoria.
– Mild CNS depression, significant in toxicity.
– Renal insufficiency.
Dosing.
– 150mg/day start. (Divided doses either 2x or 3x/day).
• Lower in renal impairment
• Titrate every 3-7 days by 150mg/day if tolerated.
• Max 600mg/day.
Tramadol
Good for mixed nociceptive and neuropathic pain
Pro’s
– Severe pain
• Weak agonist
• O-desmethyl metabolite - mu agonist
– Less respiratory depression
– Neuropathic pain
• inhibits the reuptake of norepinephrine and serotonin in the CNS
Con’s
– Drug interactions
• carbamazepine, quinidine, TCA, and SSRI’s
• Serotonin syndrome
– SE
• dizziness, GI, constipation
• Seizure risks
– Abuse potential (Less?)
Dosing:
• IR–50mgq4hprn
• ER – Naïve: 100mg daily
– 300mg max/day
Can be used PRN
