As lidocaine and ketamine provide analgesia by acting on different molecular pathways, administering them together may produce synergistic effects, which can allow for using a lower dose of each medication and thereby reducing the corresponding side effects. To the investigator's knowledge, despite the common practice of multimodal analgesia, lidocaine-ketamine infusions have never been studied prospectively in an out of hospital setting to treat neuropathic pain. The aim of the present study is to evaluate the effectiveness of the current routine practice of lidocaine-ketamine infusions conducted at Allevio Pain Management Clinic, a large outpatient community based chronic pain management facility. Lidocaine-ketamine infusions are prescribed to patients that have pain that is considered to be neuropathic for which standard anti-neuropathic medications have been ineffective or poorly tolerated by patients. A prospective longitudinal study.

Study objectives

1. To evaluate effectiveness of lidocaine-ketamine infusions in reducing neuropathic pain, as assessed using the Revised Pain Quality Assessment Scale (PQAS-R) and Short Form Brief Pain Inventory (BPI-SF).
2. To evaluate the effects of lidocaine-ketamine infusions on the measures of Global Improvement and Satisfaction Score, Pain Self-Efficacy Questionnaire (PSEQ), Pain Catastrophic Scale (PCS), Beck Depression Inventory (BDI), and Patient self-reported perceived duration of effect (PSPDE).
3. To assess, analyze, and report adverse events

The study will be conducted per IMMPACT recommendations (17). Multi variable parameters will be captured: pain unpleasantness, physical function, emotional function, global improvement and satisfaction with treatment, adverse events and disposition. Additional instruments will be used in the triage process and follow-up (S-LANSS, PSEQ).

Number of subjects: all eligible consecutive patients accepted for lidocaine-ketamine infusions over period of 6 months.

Patients with multi focal and/or non-dermatomal pain with neuropathic component will be included.

Dosing and infusion orders are completed by one of the physician-investigators prior to patient arrival based on body weight, and modified if required after individual evaluation. Based on published literature and clinical impression, higher doses seem to be more effective and result in longer pain relief. Therefore, subsequent infusion doses will be increased to the maximally tolerated doses (i.e. minimal side effects).

Doses will be calculated using the following:

• Lidocaine - initial dose of 5.0 mg/kg +/- 1.0 mg/kg (based on actual weight, up to maximum dose 600 mg) over 45 minutes, followed by increases of 0.5 mg/kg each infusion based on tolerability of side effects, not to exceed 7 mg/kg or 600 mg.
• Ketamine - initial dose of 0.1 mg/kg (based on actual weight) over 45 minutes (rounded to nearest 5 mg, up to maximum 15 mg), increased by 0.1 mg/kg (rounded to nearest 5 mg) each infusion based on tolerability of side effects.

Standard clinic procedure will be followed for completing the infusions and managing side effects. The infusion will be initiated at 360 ml/hour for planned completion in 45 minutes, rate adjusted if side effects develop. Total doses of medication are recorded in the medical record.

Data collection and Management All study tools will be completed by patients online using, or in the clinic RedCap system. RedCap is a mature, secure web application for building and managing online surveys and databases (Vanderbilt University). The system is secured by SSL protocol and data is encrypted. Patients will be contacted via Email with a secure link to RedCap database, or if they would not be able to do it at home research, they can complete the questionnaires with research coordinator's assistant in secure computers at the clinic. Participant will receive reminders about upcoming visits and promoted to complete the follow-up forms. Allevio data protection is also SSL enabled and secured by SHA256, and they are issued by Rapid SSL and purchased through Ceerts4Less.

Inclusion Criteria:

Pain duration > 3 months;

Multifocal and/or non-dermatomal neuropathic pain per Pain Diagram;

Failed medical management with at least 2 neuromodulation agents (e.g., gabapentinoids, antidepressants, cannabinoids);

Neuropathic component (12 or more points on S-LANSS);

Exclusion Criteria:

Non-English speakers;

Refusal to sign informed consent;

Allergy to ketamine and/or lidocaine;

Known relative contraindications to ketamine use which include poorly controlled systemic illnesses: hypertension, hyperthyroidism, ischemic heart disease, heart failure, psychiatric comorbidity (e.g., psychosis, schizophrenia, dissociative state);

Known contraindication to lidocaine use which include current symptomatic or clinically significant brady- or tachyarrhythmia, systolic blood pressure <90 or >180 mmHg;

Scheduled interventions targeting neuropathic pain: epidural injections, peripheral nerve blocks, Bier block, radiofrequency of dorsal root ganglia and peripheral nerves, additional lidocaine or ketamine infusions;

Newly added analgesic or neuromodulating medications within 30 days;

Recently performed neuromodulating interventions within 90 days;

Previous lidocaine-ketamine, lidocaine or ketamine infusion within 6 months;

Acute intoxication or active illegal substance abuse;