Neuropathic Pain Management¶

VERSION: 1.1 CREATED: February 8, 2026 REVISED: February 8, 2026 STATUS: Draft - Revised per checker/rebuilder pipeline

DIAGNOSIS: Neuropathic Pain

ICD-10: G89.29 (Other chronic pain), G89.4 (Chronic pain syndrome), G89.0 (Central pain syndrome), G60.9 (Hereditary and idiopathic neuropathy, unspecified), G62.9 (Polyneuropathy, unspecified), M79.2 (Neuralgia and neuritis, unspecified), B02.22 (Postherpetic trigeminal neuralgia), B02.29 (Other postherpetic nervous system involvement), G50.0 (Trigeminal neuralgia), E11.42 (Type 2 diabetes with diabetic polyneuropathy), G63 (Polyneuropathy in diseases classified elsewhere)

CPT CODES: 85025 (CBC), 80048 (BMP), 80076 (Hepatic function panel), 82947 (Glucose), 83036 (HbA1c), 93000 (ECG), 80195 (Phenytoin level), 80156 (Carbamazepine level), 95907-95913 (Nerve conduction studies, 1-13+ studies), 95886 (Needle EMG, complete), 99213-99215 (Office visit), 99281-99285 (ED visit), 64450 (Peripheral nerve block), 64555 (Peripheral nerve stimulator implant), 63650 (Spinal cord stimulator trial), 63685 (Spinal cord stimulator permanent implant), 62350 (Intrathecal drug delivery implant), 64633-64636 (Radiofrequency ablation), 96365 (IV infusion, initial hour — lidocaine/ketamine), 96374 (IV push), 96372 (Therapeutic injection), 20553 (Trigger point injection), 36000 (IV access for infusion)

SYNONYMS: neuropathic pain, nerve pain, neurogenic pain, neuralgia, painful neuropathy, diabetic neuropathic pain, painful diabetic neuropathy, post-herpetic neuralgia, PHN, central pain syndrome, thalamic pain, post-stroke pain, central post-stroke pain, spinal cord injury pain, SCI pain, chemotherapy-induced neuropathic pain, CIPN, painful polyneuropathy, allodynia, hyperalgesia, dysesthesia, trigeminal neuralgia, MS-related pain, neuropathic pain syndrome, chronic neuropathic pain

SCOPE: Treatment-focused plan for neuropathic pain management in adults. Covers peripheral neuropathic pain (diabetic, post-herpetic, traumatic, chemotherapy-induced) and central neuropathic pain (post-stroke, spinal cord injury, MS-related). Includes pain screening tools (DN4, LANSS), step therapy per AAN/EFNS/NeuPSIG guidelines, combination therapy strategies, opioid risk assessment, interventional options, and deprescribing guidance. Covers ED acute exacerbation, inpatient management, and outpatient chronic care. Excludes diagnostic workup for neuropathy etiology (covered in neuropathy-specific plans).

DEFINITIONS: - Neuropathic Pain: Pain caused by a lesion or disease of the somatosensory nervous system; characterized by burning, shooting, electric shock-like quality, allodynia, or hyperalgesia - Central Pain Syndrome: Neuropathic pain arising from a lesion or disease of the central somatosensory nervous system (e.g., post-stroke thalamic pain, spinal cord injury pain, MS-related pain) - Peripheral Neuropathic Pain: Pain arising from a lesion or disease of peripheral somatosensory neurons (e.g., diabetic neuropathy, post-herpetic neuralgia, traumatic nerve injury) - Allodynia: Pain due to a stimulus that does not normally provoke pain (e.g., light touch) - Hyperalgesia: Increased pain from a stimulus that normally provokes pain - DN4 (Douleur Neuropathique 4): 10-item screening questionnaire; score >=4/10 indicates neuropathic pain (sensitivity 83%, specificity 90%) - LANSS (Leeds Assessment of Neuropathic Symptoms and Signs): 7-item tool; score >=12/24 suggests neuropathic pain - NRS (Numeric Rating Scale): 0-10 pain intensity scale; 0 = no pain, 10 = worst pain imaginable - NNT (Number Needed to Treat): Number of patients who need to be treated to achieve one additional good outcome (>=50% pain relief)

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

1. LABORATORY WORKUP¶

1A. Core Labs (Monitoring for Treatment)¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
BMP (CPT 80048)	ROUTINE	ROUTINE	ROUTINE	ROUTINE	Renal function for dose adjustment (gabapentinoids, tramadol); electrolytes	Normal eGFR; normal electrolytes
CBC (CPT 85025)	ROUTINE	ROUTINE	ROUTINE	ROUTINE	Baseline before carbamazepine/oxcarbazepine (agranulocytosis risk)	Normal WBC, platelets
Hepatic panel (CPT 80076)	ROUTINE	ROUTINE	ROUTINE	ROUTINE	Baseline before duloxetine, TCAs; hepatotoxicity monitoring	Normal ALT/AST/bilirubin
HbA1c (CPT 83036)	ROUTINE	ROUTINE	ROUTINE	-	Glycemic control in diabetic neuropathic pain; treatment target	< 7.0%
Urine drug screen (CPT 80307)	ROUTINE	ROUTINE	ROUTINE	-	Opioid risk assessment; compliance monitoring; identify unreported substances	Consistent with prescribed medications

1B. Extended Labs (Based on Treatment Selection)¶

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
ECG (CPT 93000)	STAT	ROUTINE	ROUTINE	STAT	Baseline before TCAs (QTc prolongation risk); cardiac monitoring	QTc < 500 ms; no conduction abnormality
Sodium level	-	ROUTINE	ROUTINE	-	Monitor for hyponatremia with carbamazepine, oxcarbazepine, SNRIs	Na > 130 mEq/L
Carbamazepine level (CPT 80156)	-	ROUTINE	ROUTINE	-	Therapeutic drug monitoring for trigeminal neuralgia treatment	4-12 mcg/mL
HLA-B*1502 genotype	-	EXT	ROUTINE	-	Pre-carbamazepine/oxcarbazepine in patients of Southeast Asian descent (SJS/TEN risk)	Negative
Lipid panel	-	-	ROUTINE	-	Metabolic monitoring with pregabalin (weight gain); cardiovascular risk	Normal

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Pain Assessment Tools (Essential)¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Numeric Rating Scale (NRS 0-10)	STAT	STAT	ROUTINE	STAT	Every encounter; q4h inpatient	Document baseline and response; target >=30% reduction	None
DN4 Questionnaire	ROUTINE	ROUTINE	ROUTINE	-	Initial assessment; confirm neuropathic mechanism	Score >=4/10 = neuropathic pain	None
LANSS Pain Scale	-	ROUTINE	ROUTINE	-	Initial assessment if DN4 equivocal	Score >=12/24 = neuropathic pain	None
Brief Pain Inventory (BPI)	-	ROUTINE	ROUTINE	-	Baseline and follow-up; functional impact	Document interference with ADLs	None
Opioid Risk Tool (ORT)	ROUTINE	ROUTINE	ROUTINE	-	Before any opioid prescribing	Low (0-3), moderate (4-7), high (>=8)	None
PDMP check (Prescription Drug Monitoring Program)	ROUTINE	ROUTINE	ROUTINE	-	Before prescribing controlled substances	No concerning patterns	None

2B. Extended Studies (Select Cases)¶

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI brain/spinal cord	-	EXT	EXT	-	If central pain suspected (post-stroke, MS, SCI)	Identify CNS lesion correlating with pain	Pacemaker, metal
EMG/NCS (CPT 95907-95913)	-	-	ROUTINE	-	If neuropathy type uncertain; guide treatment selection	Characterize nerve injury pattern	None (relative: anticoagulation for needle EMG)
Quantitative sensory testing (QST)	-	-	EXT	-	Research; difficult-to-characterize pain	Small fiber dysfunction	None

3. TREATMENT¶

3A. Acute Pain Exacerbation¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
IV lidocaine infusion	IV	Severe refractory neuropathic pain crisis; inpatient only	1-3 mg/kg :: IV :: once over 30-60 min :: Infuse 1-3 mg/kg over 30-60 min; may repeat once in 24h; cardiac monitoring required	Cardiac arrhythmia, heart block, hepatic failure, seizure disorder	Continuous cardiac monitoring; BP q15min during infusion; lidocaine level if repeated	URGENT	URGENT	-	URGENT
Ketorolac	IV/IM	Acute exacerbation with inflammatory component; short-course only	15 mg; 30 mg :: IV :: q6h :: 15-30 mg IV/IM q6h; max 5 days; use lowest effective dose	Renal impairment, GI bleeding, coagulopathy, age >65 (use 15 mg)	Renal function; GI symptoms	STAT	ROUTINE	-	STAT
Ketamine (subanesthetic)	IV	Severe refractory neuropathic pain; opioid-resistant pain crisis	0.1-0.3 mg/kg/hr :: IV :: continuous :: 0.1-0.3 mg/kg/hr infusion; max 72h; monitor for dissociative symptoms	Uncontrolled HTN, raised ICP, psychosis, pregnancy	BP, HR, dissociative symptoms, hepatic function if >24h	-	URGENT	-	URGENT
Morphine (short-course crisis)	IV	Severe acute exacerbation unresponsive to non-opioid measures; bridge only	2 mg; 4 mg :: IV :: q3-4h PRN :: 2-4 mg IV q3-4h PRN; max 48-72h; document exit plan	Respiratory depression, concurrent benzodiazepines, substance use disorder, untreated sleep apnea	Respiratory rate, sedation scale, SpO2	STAT	URGENT	-	STAT
Dexamethasone (acute nerve compression)	IV	Acute nerve compression or inflammation contributing to pain	4-10 mg :: IV :: daily :: 4-10 mg IV daily x 3-5 days; taper if >5 days	Active infection, uncontrolled diabetes	Blood glucose; GI symptoms	URGENT	ROUTINE	-	URGENT

3B. First-Line Agents --- Gabapentinoids¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Gabapentin	PO	Peripheral neuropathic pain (diabetic, PHN); first-line; NNT 6.3	300 mg qHS; 300 mg TID; 600 mg TID; 900 mg TID; 1200 mg TID :: PO :: TID :: Start 300 mg qHS; titrate by 300 mg q3-7 days; target 1800-3600 mg/day in 3 divided doses; reduce dose if CrCl <60	Severe renal impairment (adjust dose); history of substance use (abuse potential)	Sedation, dizziness, peripheral edema, renal function; suicidal ideation (FDA warning)	-	ROUTINE	ROUTINE	-
Pregabalin	PO	Peripheral neuropathic pain (diabetic, PHN, SCI); first-line; NNT 7.7 for diabetic neuropathy	75 mg BID; 150 mg BID; 300 mg BID :: PO :: BID :: Start 75 mg BID; titrate to 150 mg BID at week 1; max 300 mg BID (600 mg/day); reduce if CrCl <60	Severe renal impairment (adjust dose); schedule V controlled substance	Sedation, dizziness, weight gain, peripheral edema; suicidal ideation (FDA warning)	-	ROUTINE	ROUTINE	-

3C. First-Line Agents --- SNRIs¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Duloxetine	PO	Diabetic neuropathic pain (FDA approved); also effective for other peripheral neuropathic pain; NNT 6.4	30 mg daily; 60 mg daily :: PO :: daily :: Start 30 mg daily x 1 week; increase to 60 mg daily; max 120 mg/day; take with food	Hepatic impairment, CrCl <30, concurrent MAOIs, uncontrolled narrow-angle glaucoma	BP, hepatic function, sodium, nausea, sexual dysfunction; serotonin syndrome risk with other serotonergic agents; taper over 2 weeks to discontinue	-	ROUTINE	ROUTINE	-
Venlafaxine XR	PO	Neuropathic pain (various types); effective at higher doses (>=150 mg); NNT 6.4	37.5 mg daily; 75 mg daily; 150 mg daily; 225 mg daily :: PO :: daily :: Start 37.5 mg daily x 1 week; titrate by 37.5-75 mg weekly; target 150-225 mg/day; analgesic effect requires >=150 mg	Uncontrolled HTN, concurrent MAOIs, severe hepatic/renal impairment	BP (dose-dependent HTN), sodium, serotonin syndrome risk; taper over 2-4 weeks to discontinue	-	ROUTINE	ROUTINE	-

3D. First-Line Agents --- TCAs¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Amitriptyline	PO	Neuropathic pain (all types); first-line; NNT 3.6; also effective for central pain	10 mg qHS; 25 mg qHS; 50 mg qHS; 75 mg qHS :: PO :: qHS :: Start 10-25 mg qHS; titrate by 10-25 mg q1-2 weeks; target 50-75 mg qHS; max 150 mg/day; give at bedtime	Cardiac conduction defects, recent MI, concurrent MAOIs, urinary retention, narrow-angle glaucoma, age >65 (use nortriptyline instead)	ECG before and after dose changes (QTc); anticholinergic effects (dry mouth, constipation, urinary retention); weight gain; sedation; fall risk in elderly	-	ROUTINE	ROUTINE	-
Nortriptyline	PO	Neuropathic pain; preferred TCA in elderly (less anticholinergic); NNT 3.6 (class)	10 mg qHS; 25 mg qHS; 50 mg qHS; 75 mg qHS :: PO :: qHS :: Start 10 mg qHS; titrate by 10-25 mg q1-2 weeks; target 50-75 mg qHS; max 150 mg/day	Cardiac conduction defects, recent MI, concurrent MAOIs, urinary retention	ECG before and after dose changes; fewer anticholinergic effects than amitriptyline; therapeutic drug level available (target 50-150 ng/mL)	-	ROUTINE	ROUTINE	-
Desipramine	PO	Neuropathic pain; least sedating TCA; preferred when daytime alertness required	25 mg daily; 50 mg daily; 75 mg daily; 100 mg daily :: PO :: daily :: Start 25 mg daily; titrate by 25 mg q1-2 weeks; target 75-100 mg/day; max 150 mg/day; may give in AM	Cardiac conduction defects, recent MI, concurrent MAOIs	ECG before and after dose changes; least anticholinergic of TCAs; may cause insomnia	-	ROUTINE	ROUTINE	-

3E. Second-Line Agents¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Tramadol	PO	Neuropathic pain when first-line agents fail or as add-on; NNT 4.7	50 mg q6h; 100 mg q6h :: PO :: q6h :: Start 50 mg q4-6h PRN; may increase to 50-100 mg q6h; max 400 mg/day; reduce to max 200 mg/day if age >75 or CrCl <30	Seizure disorder (lowers threshold), concurrent MAOIs/SSRIs/SNRIs (serotonin syndrome), substance use disorder	Serotonin syndrome symptoms, seizure risk, constipation; schedule IV controlled substance; PDMP check required; naloxone co-prescription if risk factors	-	ROUTINE	ROUTINE	-
Lidocaine 5% patch (Lidoderm)	Topical	Localized peripheral neuropathic pain (PHN, focal neuropathy); NNT 4.4 for PHN	1-3 patches :: topical :: 12h on/12h off :: Apply up to 3 patches to painful area; 12 hours on, 12 hours off; may cut to size	Allergy to local anesthetics; avoid on broken skin	Skin irritation; minimal systemic absorption; safe in elderly	-	ROUTINE	ROUTINE	-
Capsaicin 8% patch (Qutenza)	Topical	Post-herpetic neuralgia (FDA approved); localized peripheral neuropathic pain; NNT 10.6	1-4 patches :: topical :: q3 months :: Apply to painful area for 60 min (feet: 30 min); in-clinic procedure; pretreat with topical anesthetic; repeat q3 months	Allergy to capsaicin; avoid on face; avoid broken skin	Application-site pain/erythema (expected); BP monitoring during application; transient pain flare; use nitrile gloves	-	-	ROUTINE	-
Carbamazepine	PO	Trigeminal neuralgia (first-line for TN); NNT 1.7 for TN	100 mg BID; 200 mg BID; 400 mg BID; 600 mg BID :: PO :: BID :: Start 100 mg BID; titrate by 100-200 mg q3-7 days; target 400-1200 mg/day; use controlled-release formulation when available	HLA-B*1502 positive, bone marrow suppression, hepatic porphyria, concurrent MAOIs	CBC q2 weeks x 2 months then q3 months (agranulocytosis); sodium (hyponatremia); LFTs; drug level (4-12 mcg/mL); drug interactions (CYP3A4 inducer)	-	ROUTINE	ROUTINE	-
Oxcarbazepine	PO	Trigeminal neuralgia (alternative to carbamazepine); fewer drug interactions	150 mg BID; 300 mg BID; 600 mg BID; 900 mg BID :: PO :: BID :: Start 150 mg BID; titrate by 150-300 mg weekly; target 600-1800 mg/day	HLA-B*1502 positive, severe hyponatremia	Sodium q2 weeks initially then q3 months (higher hyponatremia risk than carbamazepine); fewer drug interactions than carbamazepine	-	ROUTINE	ROUTINE	-

3F. Third-Line/Refractory Agents¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Tapentadol ER	PO	Refractory neuropathic pain; dual mechanism (mu-opioid agonist + NRI); NNT 10.2	50 mg BID; 100 mg BID; 150 mg BID; 250 mg BID :: PO :: BID :: Start 50 mg BID; titrate by 50 mg BID q3 days; max 500 mg/day; do not crush ER tablets	Severe respiratory depression, concurrent MAOIs, GI obstruction, substance use disorder	Respiratory rate, sedation, constipation; schedule II controlled; PDMP check; naloxone co-prescription	-	-	ROUTINE	-
Buprenorphine transdermal (Butrans)	Transdermal	Refractory neuropathic pain; partial mu-agonist; lower abuse potential; safer respiratory profile	5 mcg/hr; 10 mcg/hr; 20 mcg/hr :: transdermal :: weekly :: Start 5 mcg/hr patch; apply q7 days; titrate q72h by one patch strength; max 20 mcg/hr	Severe respiratory depression, long QT, concurrent full opioid agonists (block effect)	Respiratory rate, QTc, sedation; ceiling effect on respiratory depression; partial agonist (precipitate withdrawal if on full agonist)	-	-	ROUTINE	-
Lamotrigine	PO	Central neuropathic pain (post-stroke, SCI, HIV neuropathy); third-line for peripheral neuropathic pain	25 mg daily; 50 mg daily; 100 mg daily; 200 mg daily; 400 mg daily :: PO :: daily-BID :: Start 25 mg daily x 2 weeks; then 50 mg daily x 2 weeks; then 100 mg daily; titrate slowly to 200-400 mg/day; halve titration rate with valproate	SJS/TEN risk (slow titration mandatory), hepatic impairment	Rash (discontinue immediately if suspected SJS); very slow titration mandatory; therapeutic range 3-14 mcg/mL for seizures (pain target uncertain)	-	ROUTINE	ROUTINE	-
Mexiletine	PO	Refractory peripheral neuropathic pain; oral sodium channel blocker; evidence limited	150 mg TID; 200 mg TID; 300 mg TID :: PO :: TID :: Start 150 mg daily with food; titrate by 150 mg q3 days; target 150-300 mg TID; max 1200 mg/day	Cardiac arrhythmia, second/third-degree heart block, cardiogenic shock	ECG before initiation and with dose changes; GI side effects common; hepatic function; drug interactions with CYP1A2 inhibitors	-	-	EXT	-
Methadone	PO	Refractory neuropathic pain; NMDA antagonist properties; long-acting; low cost	2.5 mg BID; 5 mg BID; 10 mg BID :: PO :: BID-TID :: Start 2.5 mg BID-TID; titrate slowly q5-7 days; highly variable pharmacokinetics; specialist prescribing recommended	QTc >500 ms, severe respiratory depression, concurrent benzodiazepines (relative), substance use disorder	ECG at baseline, 30 days, annually (QTc); respiratory rate; variable half-life (8-59h) requires careful titration; deaths from accumulation; PDMP check	-	-	EXT	-
Oxycodone CR (last resort)	PO	Severe refractory neuropathic pain failing all other options; documented risk assessment	10 mg BID; 20 mg BID :: PO :: BID :: Start 10 mg BID; lowest effective dose; re-evaluate q1-3 months; mandatory opioid agreement; combine with non-opioid regimen	Active substance use disorder, concurrent benzodiazepines, untreated sleep apnea	PDMP check q3 months; UDS q3-6 months; functional assessment; naloxone co-prescription mandatory; opioid agreement mandatory; document risk-benefit at each visit	-	-	EXT	-

3G. Topical Agents¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Lidocaine 5% patch (Lidoderm)	Topical	Localized peripheral neuropathic pain; first-line topical; safe in elderly and polypharmacy	1-3 patches :: topical :: 12h on/12h off :: Apply up to 3 patches to painful area; 12 hours on, 12 hours off; may cut to fit; avoid on broken skin	Allergy to local anesthetics; broken skin at application site	Local skin irritation; minimal systemic absorption; safe in elderly; no significant drug interactions	-	ROUTINE	ROUTINE	-
Capsaicin 0.075% cream	Topical	Localized neuropathic pain; OTC option; depletes substance P	Apply QID :: topical :: QID :: Apply thin layer to painful area 3-4 times daily; burning sensation decreases with regular use over 1-2 weeks; wash hands after application	Allergy to capsaicin; open wounds	Application-site burning (expected first 1-2 weeks); avoid mucous membranes and eyes; use gloves	-	ROUTINE	ROUTINE	-
Compounding cream (gabapentin/ketamine/lidocaine)	Topical	Localized neuropathic pain refractory to single-agent topicals; limited evidence	Apply BID-TID :: topical :: BID-TID :: Apply to affected area BID-TID; formulation varies by compounding pharmacy; typical: gabapentin 6%/ketamine 10%/lidocaine 5%	Allergy to components	Local irritation; limited systemic absorption; insurance coverage often denied; evidence base limited	-	-	EXT	-

3H. Interventional Therapies¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Spinal cord stimulation (SCS)	Implant	CRPS, failed back surgery syndrome, painful diabetic neuropathy (FDA approved); refractory to >=2 pharmacologic agents	N/A :: implant :: continuous :: Trial period (5-7 days) followed by permanent implant if >=50% pain relief; multiple waveform options (tonic, burst, HF10, DTM)	Active infection, coagulopathy, psychiatric instability, patient unable to manage device	Pain relief (NRS), functional status, device interrogation q6-12 months; trial success defined as >=50% pain reduction	-	ROUTINE	ROUTINE	-
Dorsal root ganglion (DRG) stimulation	Implant	CRPS type I/II, focal neuropathic pain (groin, foot, knee); superior to SCS for focal pain	N/A :: implant :: continuous :: Trial period followed by permanent implant; targets specific DRG levels	Active infection, coagulopathy; not MRI conditional for all systems	Pain scores, functional assessment, device checks; higher precision for focal pain vs. traditional SCS	-	ROUTINE	ROUTINE	-
Peripheral nerve stimulation (PNS)	Implant	Focal peripheral nerve injury pain; post-surgical neuropathic pain; occipital neuralgia	N/A :: implant :: continuous :: Percutaneous or surgical lead placement; trial then permanent; 60-day temporary PNS systems available	Active infection, coagulopathy	Pain relief, functional status; newer percutaneous systems allow office-based trials	-	ROUTINE	ROUTINE	-
Intrathecal drug delivery (ITDD)	Implant	Severe refractory neuropathic pain; failed SCS or not a candidate; cancer-related neuropathic pain	N/A :: implant :: continuous :: Intrathecal trial (bolus or catheter) before permanent pump; ziconotide (first-line intrathecal for neuropathic pain); morphine/hydromorphone (second-line); baclofen for spasticity-related pain	Active infection, coagulopathy, CSF obstruction, psychosis (ziconotide)	Pump refills q1-6 months; drug levels; infection surveillance; catheter integrity; ziconotide: CK levels, psychiatric symptoms	-	ROUTINE	ROUTINE	-
Peripheral nerve block (diagnostic/therapeutic)	Injection	Focal peripheral neuropathic pain; diagnostic localization; bridge during medication titration	N/A :: injection :: per protocol :: Ultrasound-guided; bupivacaine 0.25-0.5% with or without dexamethasone; repeat q2-4 weeks if effective	Allergy to local anesthetics, infection at site, coagulopathy	Pain relief duration; infection signs; motor block (transient); nerve injury (rare)	URGENT	ROUTINE	ROUTINE	-

3I. Central Pain Syndrome Treatments¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Lamotrigine (central pain)	PO	Central post-stroke pain (first-line); SCI pain; NNT 5.9 for central pain	25 mg daily; 50 mg daily; 100 mg daily; 200 mg daily; 400 mg daily :: PO :: daily-BID :: Start 25 mg daily x 2 weeks; then 50 mg daily x 2 weeks; then 100 mg daily; titrate slowly to 200-400 mg/day; halve titration rate with valproate	SJS/TEN risk (slow titration mandatory); hepatic impairment	Rash (discontinue immediately if suspected SJS); very slow titration mandatory; therapeutic range 3-14 mcg/mL for seizures (pain target uncertain)	-	ROUTINE	ROUTINE	-
Amitriptyline (central pain)	PO	Central post-stroke pain; SCI pain; first-line TCA for central pain	10 mg qHS; 25 mg qHS; 50 mg qHS; 75 mg qHS :: PO :: qHS :: Start 10-25 mg qHS; titrate by 10-25 mg q1-2 weeks; target 50-75 mg qHS; max 150 mg/day; give at bedtime	Cardiac conduction defects, recent MI, concurrent MAOIs, urinary retention, narrow-angle glaucoma, age >65 (use nortriptyline instead)	ECG before and after dose changes (QTc); anticholinergic effects (dry mouth, constipation, urinary retention); weight gain; sedation; fall risk in elderly	-	ROUTINE	ROUTINE	-
Pregabalin (SCI pain)	PO	Spinal cord injury pain (Level A evidence); central neuropathic pain	75 mg BID; 150 mg BID; 300 mg BID :: PO :: BID :: Start 75 mg BID; titrate to 150 mg BID at week 1; max 300 mg BID (600 mg/day); reduce if CrCl <60	Severe renal impairment (adjust dose); schedule V controlled substance	Sedation, dizziness, weight gain, peripheral edema; suicidal ideation (FDA warning); renal function	-	ROUTINE	ROUTINE	-
Gabapentin (SCI pain)	PO	Spinal cord injury pain; central neuropathic pain; alternative to pregabalin	300 mg qHS; 300 mg TID; 600 mg TID; 900 mg TID; 1200 mg TID :: PO :: TID :: Start 300 mg qHS; titrate by 300 mg q3-7 days; target 1800-3600 mg/day in 3 divided doses; reduce dose if CrCl <60	Severe renal impairment (adjust dose); history of substance use (abuse potential)	Sedation, dizziness, peripheral edema, renal function; suicidal ideation (FDA warning)	-	ROUTINE	ROUTINE	-
Nabiximols (Sativex) or medical cannabis (where legal)	PO/Spray	MS-related central neuropathic pain; refractory SCI pain; jurisdiction-dependent	Varies :: oromucosal spray or PO :: BID-TID :: Nabiximols: start 1 spray BID; titrate by 1 spray/day; max 12 sprays/day; or oral cannabis per state protocol	Psychosis, unstable cardiac disease, pregnancy, age <25 (brain development)	Psychiatric symptoms, cognitive function, dizziness; legal status varies; limited evidence base; not FDA-approved for pain in US	-	-	EXT	-

4. OTHER RECOMMENDATIONS¶

4A. Referrals & Consults¶

Recommendation	ED	HOSP	OPD	ICU	Clinical Rationale
Pain medicine specialist	ROUTINE	ROUTINE	ROUTINE	ROUTINE	Refractory pain failing >=2 first-line agents; interventional procedure candidacy; opioid management; ED consult for pain crisis
Neurology	ROUTINE	ROUTINE	ROUTINE	ROUTINE	Neuropathy characterization; central pain workup; treatment optimization
Psychiatry/Psychology	-	ROUTINE	ROUTINE	ROUTINE	Comorbid depression/anxiety (present in >50% of chronic pain patients); CBT for pain; opioid risk assessment; ICU: suicidal ideation in pain crisis
Physical therapy	ROUTINE	ROUTINE	ROUTINE	-	Desensitization therapy; TENS; graded motor imagery; functional restoration; ED: arrange outpatient PT at discharge
Addiction medicine	ROUTINE	ROUTINE	ROUTINE	-	Substance use disorder identified; opioid use disorder risk; buprenorphine transition; ED: identify and refer for opioid use disorder
Palliative care	-	ROUTINE	ROUTINE	-	Cancer-related neuropathic pain; refractory pain with functional decline; goals of care
Interventional pain specialist	-	ROUTINE	ROUTINE	-	SCS/DRG candidacy; intrathecal pump evaluation; nerve block procedures; inpatient evaluation for refractory pain

4B. Patient Instructions¶

Recommendation	ED	HOSP	OPD	Rationale
Pain diary (NRS, triggers, functional impact)	ROUTINE	ROUTINE	ROUTINE	Tracks treatment response; identifies patterns; guides medication adjustment
Set realistic expectations: goal is >=30% pain reduction and improved function, not zero pain	ROUTINE	ROUTINE	ROUTINE	Prevents treatment frustration; aligns goals with achievable outcomes
Medication adherence: take scheduled medications regularly even when pain is low	-	ROUTINE	ROUTINE	Preventive effect requires steady-state levels; PRN use alone is less effective
Do not abruptly stop gabapentinoids, SNRIs, or TCAs (taper required)	ROUTINE	ROUTINE	ROUTINE	Withdrawal seizures (gabapentinoids); discontinuation syndrome (SNRIs); cardiac risk (TCAs)
Opioid safety counseling: store securely, no sharing, disposal of unused medication, naloxone training	ROUTINE	ROUTINE	ROUTINE	Prevent diversion, accidental ingestion, overdose death; mandatory for opioid prescriptions
Naloxone (Narcan) co-prescription: obtain and keep accessible if receiving any opioid	ROUTINE	ROUTINE	ROUTINE	Reverses opioid overdose; FDA recommends co-prescribing with all opioid prescriptions
Avoid alcohol and sedatives with CNS-depressant medications	ROUTINE	ROUTINE	ROUTINE	Additive CNS depression with gabapentinoids, opioids, TCAs; respiratory depression risk
Return to ED for sudden severe pain escalation, new weakness, bowel/bladder dysfunction	ROUTINE	ROUTINE	ROUTINE	May indicate new neurologic emergency (cord compression, cauda equina)

4C. Lifestyle & Prevention¶

Recommendation	ED	HOSP	OPD	Rationale
Regular aerobic exercise (walking, swimming, cycling) 30 min x 5 days/week	-	-	ROUTINE	Level A evidence for pain reduction; improves endogenous pain modulation; reduces comorbid depression
Cognitive behavioral therapy (CBT) for chronic pain	-	-	ROUTINE	Level A evidence as adjunct; reduces pain catastrophizing; improves coping and function
Sleep hygiene optimization	-	ROUTINE	ROUTINE	Poor sleep amplifies pain perception; sleep disorders common in chronic pain; may reduce medication needs
Glycemic control optimization (diabetic neuropathic pain)	-	ROUTINE	ROUTINE	Prevents neuropathy progression; HbA1c <7% associated with reduced pain severity
Smoking cessation	-	ROUTINE	ROUTINE	Smoking worsens neuropathy and pain perception; impairs microvascular circulation
Weight management	-	-	ROUTINE	Reduces mechanical nerve compression; improves metabolic syndrome; enhances mobility
Mindfulness-based stress reduction (MBSR)	-	-	ROUTINE	Moderate evidence for chronic pain; reduces pain unpleasantness; complements pharmacotherapy

4D. Combination Therapy Strategies¶

Combination	Evidence	Monitoring Notes
Gabapentinoid + SNRI (e.g., gabapentin + duloxetine)	Level A; superior to monotherapy in COMBO-DN trial	Additive sedation; monitor for dizziness, falls
Gabapentinoid + TCA (e.g., pregabalin + nortriptyline)	Level B; effective but requires cardiac monitoring	ECG at baseline and with TCA dose changes; additive sedation and anticholinergic effects
TCA + topical (e.g., amitriptyline + lidocaine patch)	Level C; reasonable for localized pain with sleep disruption	Minimal systemic interaction; monitor anticholinergic burden
SNRI + topical (e.g., duloxetine + capsaicin 8% patch)	Level C; practical combination for localized + diffuse pain	Minimal interaction; SNRI provides systemic coverage
Gabapentinoid + tramadol	Level B; short-term combination data	Seizure threshold lowering (additive); sedation; limit tramadol duration
Do NOT combine: TCA + SNRI	Contraindicated; serotonin syndrome risk; excessive norepinephrine effect	If switching, allow adequate washout period

4E. Deprescribing Guidance¶

Scenario	Strategy	Timeline
Ineffective medication (no response after adequate trial at therapeutic dose)	Taper and discontinue; document lack of efficacy	Gabapentinoids: taper over 1-2 weeks; SNRIs: taper over 2-4 weeks; TCAs: taper over 2-4 weeks
Opioid reduction for stable chronic neuropathic pain	Optimize non-opioid regimen first; reduce opioid by 10% of total daily dose q2-4 weeks	10% reduction q2-4 weeks; slower if withdrawal symptoms; pause taper if pain significantly worsens
Opioid rotation (inadequate relief or intolerable side effects)	Calculate morphine milligram equivalents (MME); convert at 50-75% of equianalgesic dose; cross-tolerance incomplete	Complete transition over 3-7 days; close monitoring during rotation
Polypharmacy reduction (patient on >3 pain medications)	Eliminate least effective agent first; maintain agents with dual benefit (e.g., SNRI for pain + depression)	One change at a time; reassess in 2-4 weeks before next change

5. DIFFERENTIAL DIAGNOSIS¶

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Nociceptive pain (inflammatory, mechanical)	Aching/throbbing quality; localized to joint/tissue; responds to NSAIDs; no burning/electric quality	DN4 <4; responds to anti-inflammatory agents; normal nerve exam
Fibromyalgia	Widespread pain (not dermatomal); fatigue; cognitive dysfunction; tender points; no nerve distribution	ACR criteria; DN4 often <4; normal NCS/EMG; normal neurologic exam
Vascular pain (ischemic)	Claudication pattern; pallor/cyanosis; diminished pulses; worsens with exertion	ABI (ankle-brachial index); vascular duplex; angiography
Radiculopathy	Dermatomal distribution; worsens with Valsalva; positive straight leg raise; motor/reflex changes	MRI spine; EMG/NCS; dermatomal pain pattern
Complex regional pain syndrome (CRPS)	Limb edema, color/temperature changes, trophic changes; disproportionate to inciting event; Budapest criteria	Budapest diagnostic criteria; bone scan (early); no specific lab test
Psychogenic pain / somatic symptom disorder	Non-anatomical distribution; inconsistent exam; significant psychosocial stressors; does not follow neurologic patterns	Psychiatric evaluation; normal investigations; DN4 <4; diagnosis of exclusion
Myofascial pain	Trigger points; taut bands; referred pain patterns; responds to trigger point injection	Physical examination; trigger point identification; normal NCS/EMG
Phantom limb pain	Post-amputation; pain felt in absent limb; burning/cramping quality	History of amputation; clinical diagnosis

6. MONITORING PARAMETERS¶

Parameter	ED	HOSP	OPD	ICU	Frequency	Target/Threshold	Action if Abnormal
Pain intensity (NRS 0-10)	STAT	q4-8h	Every visit	q4h	Per setting	>=30% reduction from baseline	Adjust regimen; consider escalation or combination therapy
Functional assessment (BPI interference, ADL status)	-	Weekly	Every visit	-	q1-3 months	Improved or stable function	Reassess treatment goals; consider rehabilitation referral
PDMP check	ROUTINE	At admission	Every visit with controlled substance	ROUTINE	Before each controlled substance prescription	No concerning patterns (multiple prescribers, escalating doses)	Address directly; consider addiction medicine referral
Urine drug screen	ROUTINE	At admission if on opioids	q3-6 months if on opioids	ROUTINE	q3-6 months for opioid patients	Consistent with prescribed; negative for illicit	Discuss discrepancies; adjust treatment plan; consider taper
Sedation assessment (Pasero scale or similar)	STAT	q4h if on opioids	Every visit	q2h	Per setting	Alert and oriented; no excessive sedation	Hold opioid dose; reduce; naloxone if severe
Renal function (eGFR)	ROUTINE	Weekly	q6-12 months	ROUTINE	Based on agent	Normal for gabapentinoid/tramadol dosing	Adjust doses per renal dosing guidelines
ECG (QTc)	STAT	After TCA dose change	At TCA initiation and dose changes; q6-12 months on methadone	STAT	Per agent	QTc <500 ms	Reduce dose or switch agent if QTc prolonged
CBC (if on carbamazepine/oxcarbazepine)	-	Weekly x 2 months	q3 months	-	q3 months after initial period	Normal WBC and platelets	Hold and consult hematology if WBC <3000 or ANC <1500
Sodium (if on carbamazepine, oxcarbazepine, or SNRIs)	-	Weekly	q3 months	-	q3 months	Na >130 mEq/L	Reduce dose or switch agent; fluid restriction if mild
Weight and metabolic parameters (pregabalin, TCAs)	-	-	q3-6 months	-	q3-6 months	Stable weight; no metabolic syndrome	Dietary counseling; consider switch if >7% weight gain
Suicidal ideation screening (PHQ-9 item 9)	ROUTINE	Weekly	Every visit	ROUTINE	Every encounter	No suicidal ideation	Psychiatric referral; safety plan; adjust medications

7. DISPOSITION CRITERIA¶

Disposition	Criteria
Discharge from ED	Acute exacerbation managed; pain at tolerable level; no new neurologic deficits; oral medications effective; reliable follow-up within 1-2 weeks
Admit to hospital	Pain crisis unresponsive to oral medications; IV infusion required (lidocaine, ketamine); new neurologic deficits requiring workup; suicidal ideation related to pain; opioid complications
ICU admission	IV ketamine infusion requiring close monitoring; hemodynamic instability; respiratory depression from opioids; severe autonomic instability
Pain clinic referral	Chronic neuropathic pain failing >=2 first-line agents; interventional procedure candidate; complex medication management; opioid taper guidance
Outpatient neurology follow-up	New neuropathic pain diagnosis; treatment optimization; neuropathy characterization needed; central pain syndrome management
Addiction medicine referral	Opioid use disorder identified; aberrant drug behaviors; PDMP or UDS concerns; buprenorphine transition candidacy
Physical therapy/rehabilitation	Functional limitation from pain; desensitization therapy; TENS trial; graded exercise program

8. EVIDENCE & REFERENCES¶

Recommendation	Evidence Level	Source
NeuPSIG pharmacotherapy guidelines: gabapentinoids, SNRIs, TCAs as first-line	Strong recommendation; Level A	Finnerup NB et al. Lancet Neurol 2015;14(2):162-173
EFNS guidelines on neuropathic pain pharmacotherapy	Class I-II evidence	Attal N et al. Eur J Neurol 2010;17(9):1113-e88
AAN guidelines for painful diabetic neuropathy treatment	Level A-B recommendations	Bril V et al. Neurology 2011;76(20):1758-1765
Combination pharmacotherapy for neuropathic pain	Level A for gabapentinoid + SNRI	Gilron I et al. N Engl J Med 2005;352(13):1324-1334
Canadian guidelines for neuropathic pain management	Consensus guidelines	Moulin DE et al. Pain Res Manag 2014;19(6):328-335
Gabapentin for neuropathic pain in adults (Cochrane)	NNT 6.3 for >=50% pain relief	Wiffen PJ et al. Cochrane Database Syst Rev 2017;6:CD007938
Duloxetine for painful neuropathy (Cochrane)	NNT 6.4 for >=50% pain relief	Lunn MP et al. Cochrane Database Syst Rev 2014;1:CD007115
Pregabalin for neuropathic pain (Cochrane)	NNT 7.7 for diabetic neuropathy	Derry S et al. Cochrane Database Syst Rev 2019;1:CD007076
Lamotrigine for central post-stroke pain	Moderate evidence	Vestergaard K et al. Neurology 2001;56(2):184-190
Spinal cord stimulation for diabetic neuropathic pain	RCT evidence; superior to best medical therapy	de Vos CC et al. Pain 2014;155(11):2426-2431
Capsaicin 8% patch for neuropathic pain (Cochrane)	NNT 10.6 for PHN	Derry S et al. Cochrane Database Syst Rev 2017;1:CD007393
Opioid guidelines for chronic non-cancer pain (CDC 2022)	Guideline recommendation	Dowell D et al. MMWR Recomm Rep 2022;71(3):1-95
IV lidocaine for neuropathic pain	Moderate evidence	Moulin DE et al. Can J Anaesth 2019;66(7):820-827

NOTES¶

Neuropathic pain affects 7-10% of the general population; frequently underdiagnosed and undertreated
DN4 questionnaire is the most validated screening tool (>=4/10 = neuropathic pain; 83% sensitivity, 90% specificity)
Number needed to treat (NNT) values reflect >=50% pain reduction; NNT <10 is considered clinically meaningful
First-line agents (gabapentinoids, SNRIs, TCAs) have comparable efficacy; selection guided by comorbidities, side effect profile, and patient preference
TCAs have lowest NNT (~3.6) but highest side effect burden; avoid in elderly, cardiac disease, urinary retention
Adequate trial = therapeutic dose for >=4-8 weeks before declaring failure
Combination therapy is often necessary; best evidence for gabapentinoid + SNRI (COMBO-DN trial)
Opioids are third-line only after adequate trials of >=2 first-line agents; always document risk assessment (ORT, PDMP, UDS)
Central pain syndromes (post-stroke, SCI) may respond differently than peripheral neuropathic pain; lamotrigine has best evidence for post-stroke pain
Interventional options (SCS, DRG stimulation) should be considered before chronic opioid therapy when appropriate
Always assess and treat comorbid depression and anxiety, which amplify pain perception and impair treatment response
Deprescribing is as important as prescribing: regularly reassess and discontinue ineffective agents

CHANGE LOG¶

v1.1 (February 8, 2026) - [C1] Eliminated all cross-references in Section 3I: Lamotrigine (central pain), Amitriptyline (central pain), Pregabalin (SCI pain), Gabapentin (SCI pain) now fully self-contained with complete dosing, contraindications, and monitoring - [M2] Removed "see also 3E" cross-reference from Section 3G Lidocaine 5% patch; expanded indication, contraindications, and monitoring to be standalone - [S1] Added ED and ICU coverage for Hepatic panel in Section 1A (needed when initiating TCAs or duloxetine) - [S2] Added ED coverage for HbA1c in Section 1A (relevant for diabetic neuropathic pain assessment) - [S3] Added ED and ICU coverage for Pain medicine specialist in Section 4A (pain crisis consult) - [S4] Added HOSP coverage for Interventional pain specialist in Section 4A (inpatient refractory pain evaluation) - [S5] Added ICU coverage for Psychiatry/Psychology in Section 4A (suicidal ideation in pain crisis) - [S6] Added ED coverage for Addiction medicine in Section 4A (opioid use disorder identification) - [S7] Added ED coverage for Physical therapy in Section 4A (arrange outpatient PT at discharge) - [R1] Expanded ICD-10 codes to include neuropathy-specific codes: G60.9, G62.9, M79.2, B02.22, B02.29, G50.0, E11.42, G63

v1.0 (February 8, 2026) - Initial plan creation - NeuPSIG, AAN, EFNS guideline-based treatment algorithm - Step therapy: first-line (gabapentinoids, SNRIs, TCAs), second-line (tramadol, topicals, carbamazepine), third-line (opioids, lamotrigine, interventional) - Central pain syndrome treatment section included - Opioid risk assessment and deprescribing guidance incorporated - Combination therapy strategies and contraindicated combinations documented - 13 evidence references with PubMed links