Diode Laser as a Biomarker for Neuropathic Pain of Peripheral Origin.

The R61 will perform a four-part double-blind randomized crossover study transitioning from a pretreatment baseline phase, to randomized treatment with either lidocaine or an identical placebo patch, washout, and alternate arm. DLss measures will be obtained before and after each phase. Twice daily report of pain using a visual analogue scale will track severity of ongoing spontaneous pain in participants. The hybrid biomarker will distinguish between placebo and active treatment arms, will significantly correlate with extent of neuropathic pain reduction during lidocaine, but will not change during the placebo phase or no-treatment lead-in. If preset Go/No-Go criteria are met, the subsequent R33 validation will then compare lidocaine patch and placebo treatment in a blinded, randomized parallel arm study.

Inclusion Criteria: Inclusion criteria for Objective 1 (Healthy Controls) 1. 18-70 years of age 2. no complaints of peripheral neuropathy or other foot pain 3. no medical history of disease or medication use associated with peripheral neuropathy (e.g. diabetes) 4. DLss 3-questions and sharp sensation testing indicate neuropathy is not present. 4a Do you have persistent numbness or tingling in your feet? 4b Do you have pain in your feet that is not due to an orthopedic injury or lesions to skin/toenails? 4c Do you have problems with your balance? 5) no known allergy to lidocaine Inclusion Criteria for Objective 2 - Neuropathy Correlation 1. . 18 years of age and older 2. Length dependent, sensory predominant, peripheral neuropathy from any non-acute acquired cause (e.g. diabetes, pre-diabetes, chemotherapy induced), OR musculoskeletal pain from plantar fasciitis or ankle sprain. Inclusion Criteria for Cross Over 1. 18 years old or older: 2. Pain rating on Average Visual Analog Scale (VAS) \> 30mm or Worst Visual Analog Scale (VAS) \> 40mm 3. UENS score greater than or equal to 4 or a length dependent, sensory predominant, peripheral neuropathy from any non-acute acquired cause based on the opinion of the investigator: Exclusion Criteria: 1. Current peripheral neuropathy that is rapidly changing (e.g. Guillain Barre syndrome or glucose correction neuropathy) : 2. Severe liver disease (ie: untreated/active hepatitis) : 3. Currently receiving chemotherapy: 4. Recent or planned change in neuropathic pain medication during study (approximately 7 weeks) : 5. Structural defects in foot that result in participant being unable to differentiate between neuropathic pain and another source of pain (ie: plantar fasciitis, arthritis) : 6. Unable to comply with protocol requirements or is at undue risk as judged by the investigator : Exclusion Criteria for Patch Cross Over 1. Known allergy to topical lidocaine or other patch ingredients (ie adhesive, butylated hydroxytoluene, dipropylene glycol, silicon dioxide, styrene/isoprene/sytrene copolymer): 2. Use of topical lidocaine patch or other topical neuropathic pain creams on feet (e.g. capsaicin) : 3. Taking medications similar to lidocaine or with anti-arrhythmic properties (ie: tocainide or mexiletine) : 4. Known allergy to lidocaine or other para-aminobenzoic acid derivative (e.g. procaine, tetracaine, benzocaine) :