Neuropathic Pain Flashcards
Neuropathic
Pain caused by a lesion or a disease of the somatosensory
system
● Peripheral - e.g., painful diabetic neuropathy, post-herpetic
neuralgia, carpal tunnel syndrome, trigeminal neuralgia
● Central - e.g., post-stroke, multiple sclerosis, spinal cord
injury
● Mixed - e.g., amyloidosis, vitamin deficiencies, chemical toxins
Pain may be a manifestation of nerve injury, but there are
few predictors to indicate which patients will develop this
complication
neuropathy may not always be painful
Neuropathic Pain
describe
Pain may be spontaneous or stimulus evoked
Often described as burning, tingling, sharp, or stabbing
Paresthesia/dysesthesia, allodynia, hyperalgesia are
common
No single sign or physical finding is diagnostic
● ~ 50% of patients with musculoskeletal pain use words that
are commonly associated with neuropathic pain to describe
Non-pharmacologic Treatment
● Psychological (e.g., CBT)
● Physiotherapy
● Exercise
● Stress management
● Education
Chronic Neuropathic Pain
Management
gabapentinoids / TCA/SNRI
then tramadol / opioids
cannabinoids
4th line agents (topical lidcoane, methadone, lamotrigine)
No NSAIDS, acetaminphen
Dont typically respond
Unless for mixed pain
Painful Diabetic Neuropathy
Damage of the nerves and blood vessels in arms or legs
Often present with gradual onset of paresthesias and
pain in legs and feet
Allodynia and burning pain are common and often worse
at night
Examination will often show graded distal sensory loss
Good glycemic control can prevent appearance and
worsening
1st Line
→ Gabapentinoids, SNRIs, TCAs
● Are one of these options preferred?
Evidence
Duloxetine and pregabalin appear similarly effective for
diabetic peripheral NeP for ≥ 50% pain reduction (open label RCT)
with similar rates of patients experiencing any AE
Pregabalin and amitriptyline appear similarly effective for
≥ 50% pain reduction in patients with diabetic NeP, but
pregabalin associated with fewer AE (crossover RCT without ITT)
● NNH 3 for amitriptyline
Duloxetine and amitriptyline appear similarly effective for
≥ 50% pain reduction in patients with diabetic NeP, but
duloxetine appears better tolerated
What about combinations of 1st line therapy?
Combination of TCA or SNRI with gabapentinoid might
reduce diabetic NeP more than either alone in patients
who respond to monotherapy, but might not in patients
who do not respond to monotherapy
Amitriptyline most common AE drowsiness
Switch to duloxetine if no effect of pregab
If partial effect from pregab add on duloxetine
2nd Line
tramadol, other opioids (most studied: morphine, oxycodone)
May consider during acute exacerbations or when other
options ineffective
Shown to have a modest effect in peripheral NeP
less beneficial the more cnetral the pain is
Challenges with long-term use (AEs, misuse, etc)
if opioids do show benefit, it is a 30% improvement, not 50%
some list it as 3rd or 4th line
trials with combination thearpy
Started on either ami, pregab or dulox
1st 6 wks, if pain score 3 or less
If not there, would add 2nd agent
No diff in intiial agent used
2nd agent led to further decrease in pain
Not much diff between the combinations either
All similar in reducing pain
3rd Line
→ Cannabinoids
Chronic neuropathic pain conditions are where
cannabinoids have shown the most promise
Evidence to suggest a modest effect on neuropathic pain
dosing trial is similar to chronic pain
pdt with THC and CBC may be more beneficial than nabilone
4th Line Agents
SSRIs (citalopram, paroxetine, escitalopram)
● Show limited effect on NeP
Topicals (lidocaine, capsaicin) → will come back to these
Methadone
● May be useful
● Challenges with use
Postherpetic Neuralgia
Long lasting complication of reactivation of Varicella
Zoster Virus
● Postherpetic neuralgia = pain persisting > 3
months beyond rash duration
● Occurs in 10-50% of patients who experience this
Pain may rarely occur months to years after
resolution of acute herpes zoster episode and can be
associated with a precipitating factor (e.g., surgery)
Herpes Zoster (Shingles
● Risk factors for activation:
○ Age > 50 years (risk ↑ with age due to ↓ immune control of VZV)
○ Decreased immunologic competence
● Presents as severe or stabbing pain and dysesthesia
followed by a blistering skin eruption
○ Rash typically resolves in 2-4 weeks
● Pain can persist > 4 weeks after healing
● Main pain-related goals of treatment of herpes zoster:
○ Relieve acute pain
○ Prevent postherpetic neuralgia
● Treatment involves a 7 day course of antivirals and
24 analgesics for management of acute pain
Herpes Zoster (Shingles)
Acute pain treatment
● Mild
○ APAP
○ NSAIDs
● Moderate - Severe
○ Tramadol
○ Strong opioids
○ Topical lidocaine (NOT topical capsaicin here)
Capsaicin causes buring and acute pain can feel like brunign too
○ Consider adjuvant with gabapentinoid or TCA
Cannot just start out w gabapentinoid or TCA
- Taks a while for it to start working
This is acute pain
○ Prednisone (if severe)
25 ■ (60 mg/d x 7, then 30 mg/d x 7, then 15 mg x 7)
May improve qol, does not speed up recovery or decrease incidence of postherpetic neuralgia
Risk factors for postherpetic neuralgia:
● Increasing age
● More severe acute pain
● Larger rash surface area
● Ophthalmic involvement
● Severe prodromal pain
Symptoms typically have unilateral and dermatomal
distribution and may be intermittent or constant
● Pain may be described as aching, burning, itchy, sharp
● Allodynia, hyperalgesia may be present
Pain can last for years and cause substantial suffering
and reduction in QOL
● For patients with severe pain 3 months after rash
onset, average duration of PHN is ~ 12 months
Pain can be discontinuous, with pain-free intervals of
varying durations
Postherpetic Neuralgia
Treatment
● First line:
○ Gabapentinoids
○ TCAs
● Second line:
○ Topical lidocaine 5% (cream or patch)
■ May be considered 1st line in older adults if concerns
about CNS effects with 1st line agents
○ Opioids
Oioids for adjuct, probably not themselves
○ Topical capsaicin 0.075%
Topical Analgesics
Lidocaine 5% cream → apply to painful area TID-QID prn
● No significant AEs when used appropriately
○ If excessive use, use on broken skin, or using an occlusive
covering, systemic AEs may develop
(e.g., bradycardia, hypotension)
● Evidence: most evidence of effectiveness is in postherpetic
neuralgia. More mixed for other NeP conditions
Capsaicin 0.075% cream → apply to painful area TID
● AE: local burning (initially), stinging, erythema, topical burn (rare)
● Evidence: for ≥ 6 weeks might reduce chronic NeP, but poorly
29 tolerated
Trigeminal Neuralgia
● Condition that causes sudden, severe, sharp, unilateral,
electric shock-like pain in lower face and jaw
● Pain can last for a variable amount of time and frequency,
and between attacks, patients are usually pain-free
● Prevalence estimated at 0.03-0.3%
● Women more likely affected; most cases in ≥ 40 years old
● There are several potential causes including (but not limited to)
neurovascular compression, MS plaques, tumors,
deformity, or may be idiopathic
● Therapy may be pharmacological or surgical
Trigeminal Neuralgia
Drug of choice:
Carbamazepine (or oxcarbazepine)
Antiepileptic drugs beneficial
Alternatives or add-ons:
● Gabapentin
● Lamotrigine
● Baclofen (with carbamazepine)
● Phenytoin
Limited evidence for non-anticonvulsants
At 4 wks, further dose increases are no likely to be due to autoinduction
More likely for disease control
Carbamazepine → Initial: 100 mg CR po BID
Usual: 200 mg - 400 mg CR po BID
● AEs include:
○ Somnolence, drowsiness, dizziness
○ Tremor, ataxia
○ Hepatotoxicity
○ Nausea/vomiting (take with food)
○ Rash, Stevens-Johnson syndrome
○ Blood dyscrasias (dose-related)
● DIs: Induces CYP 1A2, 2B6, 2C8, 2C9, 3A4. Substrate of 3A4
final notes
● HIV neuropathies, radiculopathies, and cancer
chemotherapy-induced neuropathic pain are generally
less responsive to therapy
● Combining two or more different agents may improve
analgesic efficacy and, in some situations, reduce
overall adverse effects
● Insufficient evidence to recommend any single specific
drug combination for neuropathic pain
● Adequate trials generally at least 4 weeks
● Start low and go slow
● Ensure the patient understands the goals of therapy
● Prescribe artificial saliva mouth spray with TCAs and a
bowel regimen with TCAs or opioids
● It may be possible to reduce or gradually withdraw
medication after pain is controlled and a period of relief
(1-3 months)
