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

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.