Alcohol Neurolysis and Capsaicin for Postamputation Pain (PAP)

Randomized Controlled and Observational Studies Evaluating Alcohol Neurolysis and Capsaicin for Postamputation Pain (PAP)

Postamputation pain is a complex condition that includes phantom limb pain (PLP), stump pain and residual limb pain (RLP), the latter of which may be referred from joints, the spine and inflamed bursa and tendons. PLP may have peripheral, spinal and central etiologies. The evidence of peripheral mechanisms includes the relief of both PLP and RLP during local anesthetic (LA) infusions, the relief of PLP and RLP with sympathetic blocks and neuroma injections, and the development of phantom radicular pain in amputees with a herniated disc.

Neurolysis and defunctionalization are long-lasting treatments for pain when LA blocks provide temporary benefit, being most commonly used for cancer pain (e.g., celiac plexus neurolysis). Neurolysis has also been used to treat PAP, with uncontrolled studies showing benefit for both RLP and PLP. However, there are no controlled studies demonstrating efficacy. In this small study, we will evaluate the effectiveness of alcohol neurolysis of lower extremity neuromas (femoral or saphenous; sciatic or common peroneal and/or tibial; obturator and/ or lateral femoral cutaneous when pain is in those distributions) in individuals with RLP and PLP.

For individuals with upper extremity amputation in whom non-selective neurolysis may affect the ability to use certain prosthetics that depend on functioning nerve and muscle signals, high-concentration capsaicin will be injected in an observational arm. The investigators will also examine factors associated with treatment outcome in a subset of patients (e.g., functional MRI, quantitative sensory testing).

Study Overview

• Status: Not yet recruiting
• Conditions: Postamputation Pain
• Intervention / Treatment: Procedure: Injection of alcohol near neuroma; Procedure: Injection of capsaicin 150 mcg per mL if relief with lidocaine 2%; Procedure: Lidocaine 2% injection

Detailed Description

Up to 130 patients with lower extremity amputations and PAP will be randomized by a computer-generated randomization table in a 1:1 ratio in blocks of 20 to receive peri-neuroma injections of either lidocaine 2% + 100% ethyl alcohol, or lidocaine 2% + saline, around the following neuromas: 1) Femoral, or saphenous nerve below the adductor canal; 2) sciatic, or common peroneal and/or posterior tibial beneath the popliteal fossa; 3) obturator (in above the knee amputees); and 4) lateral femoral cutaneous (in above the knee amputees). The painful neuromas to be treated will be determined by physical exam (e.g., Tinel's sign, pain reproduction during palpation or use of a prosthesis), and PLP patterns correlating with nerve distributions (e.g., a person with only foot PLP will not have the obturator or lateral femoral cutaneous neuromas injected; a patient who perceives phantom pain only in the top of their foot, or the lateral side of their ankle, may require only neurolysis of the common peroneal nerve or saphenous nerve, respectively). Those with bilateral lower extremity amputations who meet inclusion criteria for both limbs will be suballocated to have an alcohol injection on one side and a lidocaine injection on the other, in random order (estimated 10-20 patients). The side that receives local anesthetic alone and the side that receives local anesthetic and alcohol will be determined by a computer-generated random number table.

The location of the painful neuromas will be identified by physical exam and confirmed via either ultrasound or electrical stimulation (e.g., using a radiofrequency machine or nerve stimulator, with concordant stimulation in the painful area(s) ideally noted at < 0.5 volts). Patients with unilateral lower extremity amputations who meet selection criteria will be allocated via a computer-generated randomization table in blocks of 20 to receive either: 1) an injection of 2 mL lidocaine 2% at each painful neuroma over 5 minutes, followed by 1.5 mL saline within 5 minutes; or 2) 2 mL lidocaine 2% at each painful neuroma over 5 minutes followed by 1.25-3.5 mL 98-100% dehydrated ethyl alcohol (the volume depends on the voltage threshold, i.e., thresholds > 0.5 mL may warrant the 23.5 mL higher volume ). For those suballocated with bilateral lower extremity amputations, both painful sides will receive an injection of 2 mL lidocaine 2% per neuroma site over 5 minutes. Then after approximately 5 minutes, the side allocated to receive alcohol with have that side injected with 1.25-3.5 mL of 98-100% alcohol while the other side will receive 1.5 mL of normal saline; the lidocaine is given first because the alcohol can burn when injected, and normal saline has been shown to provide some therapeutic effect by washing out inflammatory cytokines and breaking up adhesive scar tissue, both of which may mediate neuroma-related pain. The injections will be performed with 20-22-gauge needles or stimulating needles (when a nerve stimulator is used), depending on the means for neuroma location.

After 6 weeks (primary endpoint) in the randomized double-blind portion, those with a negative categorical outcome (< 30% pain relief or < 4/7 on the Patient Global Impression of Change (PGIC) scale) will be unblinded to receive alternative treatments. The next follow-up for those with a successful 6-week outcome will be 12 weeks. For those with a successful 12-week outcome, the final follow-up will occur at 6 months.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Steven Paul Cohen, MD; Phone Number: 1-312-695-2500; Email: steven.cohen@northwestern.edu

Study Locations

• Ukraine
  • Lviv, Ukraine
    • First Lviv Medical Union
    • Contact: Roman Smolynets, MD; Phone Number: 380-967037175; Email: smoroman9@gmail.com
    • Contact: Email: smoroman9@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age >/= 18 years 2. At least 1 lower extremity amputation 3. Pain duration >/= 1 month 4. Either average RLP or PLP in one or both (for those who have 2 lower limbs enrolled) amputated extremities >/=4/10 5. Stable analgesic regimen over the past 10 days 6. Failure of physical therapy and at least 2 pharmacological treatments 7. At least 1 suspected painful neuroma, identified by Tinel's sign or pain with pressure or prosthetic use, referred pain in the distribution of the severed nerve, and neuropathic-type symptoms (tingling, shooting or lancinating pain)

Exclusion Criteria:

• 1. Very poorly controlled psychiatric condition (e.g., PCL-5 score > 60, > 15 on the anxiety and/or depression section of HADS) 2. Poorly controlled medical condition that would preclude participation (e.g., heart failure, uncontrolled diabetes) 3. Patients in whom targeted muscle reinnervation or a similar procedure is being considered 4. Systemic infection or infection overlying the stump 5. Clinically-relevant injury to nerve fibers proximal to the amputation 6. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alcohol neurolysis; Injection of 2 mL lidocaine 2% at each painful neuroma over 5 minutes, followed by 1.25-3.5 mL 98-100% dehydrated ethyl alcohol (the volume depends on the voltage threshold, i.e., thresholds > 0.5 mL may warrant the higher volume). In those with bilateral lower extremity amputations, one leg will receive this treatment.	Procedure: Injection of alcohol near neuroma; Injection of 98-100% alcohol over painful neuromas after lidocaine 2% injected.
Other: Capsaicin; Observational cohort for upper extremity amputees in which participants will receive 1.25-3.5 mL 150 micrograms/mL of capsaicin if they experience greater or equal to 30% pain relief after injection of 2 mL of lidocaine 2% at sites of painful neuromas.	Procedure: Injection of capsaicin 150 mcg per mL if relief with lidocaine 2%; Painful upper neuroma neuromas will be injected if patients experience at least 30% pain relief with lidocaine. These patients (upper extremity amputees) are an observational cohort.
Active Comparator: Lidocaine only; Injection of 2 mL lidocaine 2% at each painful neuroma over 5 minutes, followed by 1.5 mL saline within 5 minutes.	Procedure: Lidocaine 2% injection; Injection of Lidocaine 2% followed by normal saline; Other Names: Blinded control arm for alcohol neurolysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average phantom limb pain	Average phantom limb pain on 0-10 numerical rating scale (NRS)	6 weeks
Average residual limb pain	Residual limb pain on 0-10 numerical rating scale (NRS)	6 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Anxiety and Depression Scale (HADS)	0-21 scale measuring anxiety and depression (higher scores indicate greater disease burden, each component is measured from 0-21)	2 weeks
Hospital Anxiety and Depression Scale (HADS)	0-21 scale measuring anxiety and depression (higher scores indicate greater disease burden, each component is measured from 0-21)	6 weeks
Hospital Anxiety and Depression Scale (HADS)	0-21 scale measuring anxiety and depression (higher scores indicate greater disease burden, each component is measured from 0-21)	12 weeks
Hospital Anxiety and Depression Scale (HADS)	0-21 scale measuring anxiety and depression (higher scores indicate greater disease burden, each component is measured from 0-21)	6 months
Somatic Symptom Scale (SSS-8)	Measure of somatic symptoms from 0-32, with higher scores indicating greater disease burden	2 weeks
Somatic Symptom Scale (SSS-8)	Measure of somatic symptoms from 0-32, with higher scores indicating greater disease burden	6 weeks
Somatic Symptom Scale (SSS-8)	Measure of somatic symptoms from 0-32, with higher scores indicating greater disease burden	12 weeks
Somatic Symptom Scale (SSS-8)	Measure of somatic symptoms from 0-32, with higher scores indicating greater disease burden	6 months
Athens Insomnia Scale	Instrument measuring sleep quality scored from 0-24 with higher scores indicating greater dysfunction	2 weeks
Athens Insomnia Scale	Instrument measuring sleep quality scored from 0-24 with higher scores indicating greater dysfunction	6 weeks
Athens Insomnia Scale	Instrument measuring sleep quality scored from 0-24 with higher scores indicating greater dysfunction	12 weeks
Athens Insomnia Scale	Instrument measuring sleep quality scored from 0-24 with higher scores indicating greater dysfunction	6 months
PTSD (posttraumatic symptom disorder) checklist (PCL-5)	Instrument measuring PTSD symptoms from 0-80 with higher scores indicating greater disease burden	2 weeks
PTSD (posttraumatic symptom disorder) checklist (PCL-5)	Instrument measuring PTSD symptoms from 0-80 with higher scores indicating greater disease burden	6 weeks
PTSD (posttraumatic symptom disorder) checklist (PCL-5)	Instrument measuring PTSD symptoms from 0-80 with higher scores indicating greater disease burden	12 weeks
PTSD (posttraumatic symptom disorder) checklist (PCL-5)	Instrument measuring PTSD symptoms from 0-80 with higher scores indicating greater disease burden	6 months
European Quality of Life (EuroQoL) 5D-5L	EuroQol group instrument measuring quality of life, on 5 dimensions (Mobility, Self-care, Usual activities, Pain/discomfort, and Anxiety/depression) with 5 severity levels. Each segment is measured from 1-5 (5 indicates greater disease burden).	2 weeks
European Quality of Life (EuroQoL) 5D-5L	EuroQol group instrument measuring quality of life, on 5 dimensions (Mobility, Self-care, Usual activities, Pain/discomfort, and Anxiety/depression) with 5 severity levels. Each segment is measured from 1-5 (5 indicates greater disease burden).	6 weeks
European Quality of Life (EuroQoL) 5D-5L	EuroQol group instrument measuring quality of life, on 5 dimensions (Mobility, Self-care, Usual activities, Pain/discomfort, and Anxiety/depression) with 5 severity levels. Each segment is measured from 1-5 (5 indicates greater disease burden).	12 weeks
European Quality of Life (EuroQoL) 5D-5L	EuroQol group instrument measuring quality of life, on 5 dimensions (Mobility, Self-care, Usual activities, Pain/discomfort, and Anxiety/depression) with 5 severity levels. Each segment is measured from 1-5 (5 indicates greater disease burden).	6 months
Patient Global Impression of Change (PGIC) scale	1-7 Likert scale graded from 1 (the same or worse) through 7 (a great deal better). A score of 4 (somewhat better) accompanied by at least 30% pain relief designates a positive outcome.	2 weeks
Patient Global Impression of Change (PGIC) scale	1-7 Likert scale graded from 1 (the same or worse) through 7 (a great deal better). A score of 4 (somewhat better) accompanied by at least 30% pain relief designates a positive outcome.	6 weeks
Patient Global Impression of Change (PGIC) scale	1-7 Likert scale graded from 1 (the same or worse) through 7 (a great deal better). A score of 4 (somewhat better) accompanied by at least 30% pain relief designates a positive outcome.	12 weeks
Patient Global Impression of Change (PGIC) scale	1-7 Likert scale graded from 1 (the same or worse) through 7 (a great deal better). A score of 4 (somewhat better) accompanied by at least 30% pain relief designates a positive outcome.	6 months
Binary categorical outcome (positive or negative)	Positive outcome designated as at least 30% pain relief coupled with a PGIC score of at least 4. This will be designated for the two primary outcomes, residual limb and phantom pain.	2 weeks
Binary categorical outcome (positive or negative)	Positive outcome designated as at least 30% pain relief coupled with a PGIC score of at least 4. This will be designated for the two primary outcomes, residual limb and phantom pain.	6 weeks
Binary categorical outcome (positive or negative)	Positive outcome designated as at least 30% pain relief coupled with a PGIC score of at least 4. This will be designated for the two primary outcomes, residual limb and phantom pain.	12 weeks
Binary categorical outcome (positive or negative)	Positive outcome designated as at least 30% pain relief coupled with a PGIC score of at least 4. This will be designated for the two primary outcomes, residual limb and phantom pain.	6 months
Phantom limb pain	Average and worst phantom limb pain on 0-10 NRS	2 weeks
Residual limb pain	Average and worst residual limb pain on 0-10 NRS	2 weeks
Worst residual limb pain	Worst residual limb pain on 0-10 NRS	6 weeks
Worst phantom limb pain	Worst phantom limb pain on 0-10 NRS	6 weeks
Phantom limb pain	Average and worst phantom limb pain on 0-10 NRS	12 weeks
Residual limb pain	Average and worst residual limb pain on 0-10 NRS	12 weeks
Phantom limb pain	Average and worst phantom limb pain on 0-10 NRS	6 months
Residual limb pain	Average and worst residual limb pain on 0-10 NRS	6 months

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: First Lviv Medical Union

Publications and helpful links

General Publications

• Campbell CM, Diamond E, Schmidt WK, Kelly M, Allen R, Houghton W, Brady KL, Campbell JN. A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton's neuroma. Pain. 2016 Jun;157(6):1297-1304. doi: 10.1097/j.pain.0000000000000544.
• Zhang X, Xu Y, Zhou J, Pu S, Lv Y, Chen Y, Du D. Ultrasound-guided alcohol neurolysis and radiofrequency ablation of painful stump neuroma: effective treatments for post-amputation pain. J Pain Res. 2017 Feb 3;10:295-302. doi: 10.2147/JPR.S127157. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: February 24, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: phantom limb pain; residual limb pain; Postamputation pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Neurobehavioral Manifestations; Perceptual Disorders; Pain, Postoperative; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Phantom Limb; Organic Chemicals; Therapeutics; Drug Administration Routes; Drug Therapy; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Alcohols; Lidocaine; Ethanol; Injections
• Other Study ID Numbers: UNBROKEN-1; Neu-92-13337 (Other Grant/Funding Number: U.S. Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Contingent on case-by-case approval by Ministry of Health

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No