Mechanisms of Stimulation for Pain Alleviation

Inclusion criteria

• for study participants Adults aged 18 or older with clinically diagnosed unilateral CNP in the lower back, pelvis, or lower extremities, defined (per IASP classification) as persistent or recurrent neuropathic pain caused by a peripheral nerve lesion, history of a plausible nerve trauma, pain onset in temporal relation to the trauma, and pain distribution within the innervation territory of a peripheral nerve (or nerves).14 Negative and positive sensory symptoms or signs must be compatible with the innervation territory of the affected nerve. Can be post-traumatic, post-surgical, nerve compression, nerve ischemia, peripheral nerve injury, painful scar, nerve entrapment, mononeuropathy with or without loss of motor function Patients enrolled in this study must already have been referred for or have an existing order for PNS therapy (either Nalu or SPR SPRINT), prior to consent and enrollment in this study, as part of their routine medical care. Patients cannot receive a referral for PNS device as part of the study procedures. Positive response (at least 50% pain relief) to diagnostic nerve block(s) at the suspected site(s) of CNP. Chronic (at least 6 months duration), intractable peripheral neuropathic pain; any nociceptive pain must be less prominent than the neuropathic pian. Fluent in English writing, reading, and speaking Ability and willingness to complete online assessments Williness to refrain from physical activity for at least 7 days post-lead placement. Willingness to refrain from physical activity or exercise causing muscle and/or joint soreness for 48 hours prior to QST, illicit drugs (marijuana) for 12 hours, as-needed (PRN) pain medications (e.g., NSAIDs, acetaminophen, opioids) for 12 hours prior to QST, and alcohol and nicotine on the day of QST prior to testing\*

Exclusion criteria

• Conditions causing inability to complete assessments (education, cognitive ability, mental status, medical status) Active cancer diagnosis, active malignant neoplasm (metastatic or local) or evidence of paraneoplastic syndrome Painful polyneuropathy (e.g., metabolic, autoimmune, familial, infectious disease, environmental toxins, treatment with neurotoxic drug) Chronic central neuropathic pain (e.g., spinal cord injury, brain injury, multiple sclerosis) Peripheral vascular disease Diabetic neuropathy Another pain diagnosis affecting the CNP site that could interfere with study procedures, accurate reporting and/or could confound evaluation of study endpoints (e.g., post-herpetic neuralgia) Other active implantable devices (e.g., implantable cardioverter defibrillator, spinal cord stimulator, dorsal root ganglion stimulator, sacral nerve stimulator, deep brain stimulator, intrathecal pump) Pregnancy, breastfeeding, or planning to conceive Systemic infection or local infection at the anticipated PNS implant site Immunocompromised state Coagulation disorder, bleeding diathesis, platelet dysfunction, active anticoagulation Interventional procedure and/or surgery to treat CNP in the last 30 days (subjects should be enrolled 30 days after last procedure, for prior ablative treatment must be enrolled at least 3 months after last procedure) Untreated substance use disorder Participating in another clinical trial with an active treatment arm Numbness or loss of sensation at the bilateral thumbnails, peripheral neuropathy in the hands, circulatory or sensory problem in the hands\
• Participants with a history of Raynaud's Syndrome\
• Participants with SBP ≥150 and/or DBP ≥100\
• \*QST Inclusion/Exclusion Criteria. Participants can still be enrolled iif they have the QST-only exclusionary criteria have the QST-only exclusionary criteria, but QST will be modified based on responses Additional Exclusion Criteria for Subjects receiving PET/MRI and PET/CT imaging at Stanford: Prior radiation exposure of \>2 rem total within the last 12 months Standard contraindications that would preclude MRI including pacemakers or other electronic implants, metal foreign objects or fragments in the eye or body, and aneurysm clips. Claustrophobia Inability to understand and communicate with the investigators to complete the study related questionnaires Females with positive pregnancy test.