The investigators propose that using the Diode Laser fiber type Selective Stimulator (DLss) in patients with chemotherapy-induced peripheral neuropathy (CIPN) will allow for the assessment of changes in small-fiber pain thresholds, to identify differences between subjects who received chemotherapy and developed painful CIPN, compared to subjects who received similar chemotherapy but did not develop painful CIPN (control group).

Additionally, the investigators would like to investigate whether the response to DLss correlates with pain severity in patients with persistent painful neuropathy.

The ultimate goal of this study is to develop a non-invasive, bedside quantitative test that is specific for painful CIPN. If the investigators' initial hypothesis is confirmed, the next step would be to design a prospective longitudinal study and assess changes in DLss early after initiation of chemotherapy, to determine whether this approach can help identify early predictive parameters of painful CIPN.

Painful chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, occurring in more than 60% of patients at some point during the course of cancer treatment with commonly used drugs such as taxanes and platinum compounds. It potentially may result in severely diminished quality of life and dose reduction or/and treatment delay, which may ultimately impact survival.

The mechanisms by which chemotherapy-induced nerve damage ultimately leads to pain are poorly understood, because virtually no structural or functional differences in nerve fibers between painless and painful peripheral neuropathy have been identified. As a result, there is no reliable way to predict which patients will develop persistent painful chemotherapy-induced peripheral neuropathy.

The ultimate goal of this study is to develop a non-invasive, bedside quantitative test that is specific for painful CIPN. If our initial hypothesis is confirmed, the next step would be to design a prospective longitudinal study and assess changes in DLss early after initiation of chemotherapy, to determine whether this approach can help identify early predictive parameters of painful CIPN.

In this other interventional study, we will test the utility of the Diode Laser fiber type Selective Stimulator (DLss) to identify sensory changes that are unique to patients with painful chemotherapy induced peripheral neuropathy (CIPN) vs. controls.

Painful symptoms of CIPN develop in patients with differential nerve damage to Aδ vs C-type peripheral nerve fibers. We hypothesize that Aδ:C fiber threshold ratio, as measured by the DLss, will be different between patients with painful CIPN compared to control patients who received a similar regimen of chemotherapy, but did not develop painful CIPN. The confirmation of hypothesis may lead to a novel approach for early detection of CIPN.

Subjects: 20 evaluable patients with painful CIPN following treatment with oxaliplatin, cisplatin, paclitaxel, docetaxel (or any combination of above) will be included in painful CIPN group, and 20 controls matched by the type of chemotherapy received, who did not develop painful CIPN.

The study procedure will include a one-time visit for sensory assessments including:

1. Spontaneous pain at baseline on 0-10 Numerical Rating Scale (NRS);
2. Assessment of pain symptoms on Neuropathic pain Symptom Inventory (NPSI) and Brief Pain Inventory (BPI).
3. Assessment of mood on hospital anxiety and depression scale (HADS)
4. Quantitative sensory testing (QST): thermal detection and pain thresholds, mechanical detection threshold, temporal summation (TS), and conditioned pain modulation (CPM).

The primary outcome is the comparison of Aδ:C fiber threshold ratio between patients who have developed painful CIPN, and the control subjects.

In secondary analyses, we will generate Spearman correlation coefficient between the "Aδ:C fiber threshold ratio" and the severity of painful CIPN on NPSI scale.

Inclusion Criteria:

Group A: Painful CIPN group

• Age >18
• Distal symmetric pain distribution (both feet, with or without pain in hands).
• The pain appeared during or up to 12 weeks after treatment with oxaliplatin, cisplatin, paclitaxel, docetaxel or any combination of these.
• Score of 4 or more on Douleur Neuropathique 4 (DN4) neuropathic pain questionnaire
• Pain duration > 2 months.
• Patient report of average daily pain intensity in the last week ≥3 on 0-10 Numerical Rating Scale (NRS).
• Able and willing to sign an Institutional Review Board (IRB)-approved written informed consent.

Group B: Control group:

• Age >18
• History of cancer diagnosis, previously treated with at least 8 infusions of chemotherapy regimen that included oxaliplatin or at least 6 infusions of chemotherapy regimen that included cisplatin, paclitaxel, docetaxel, or any combination of these.
• No ongoing pain in distal symmetric distribution (subjects with symptoms and signs such as mild numbness, or vibration sensation loss are eligible to be included in the control group).
• Able and willing to sign an IRB-approved written informed consent. * Subjects in the control group will be matched by the type of previous chemotherapy to the subjects in the Painful CIPN group. An additional attempt will be made to match controls by sex, age, cancer diagnosis, and cumulative neurotoxic chemotherapy dose.

Exclusion Criteria:

• History of pre-existing painful distal symmetric polyneuropathy prior to chemotherapy.
• Alternative etiology exists for the distal painful symptoms.
• Current or previous treatment with a vinca alkaloid (e.g. vincristine, vinblastine), bortezomib, or another agent which may cause major peripheral neurotoxicity.
• Pregnant
• Concomitant medication as follows:
• Patients receiving chronic daily opioids, topical lidocaine or topical capsaicin will be excluded.
• Patients receiving as needed (PRN) analgesics, including acetaminophen, NSAIDs or short-acting opioids, will be required not to take them 48h before testing, at for at least five half-lives of the specific analgesic, at the discretion of the investigators.

In accordance with the recent proposal from the International Committee of Medical Journal Editors, patient-level data will be made available within 6 months after publication of the primary manuscript. Data will be provided to researchers who submit a methodologically sound research proposal including a protocol and statistical analysis plan. No patient-identifying fields (including dates) will be included in the shared dataset. Certain technical data related to the intellectual property rights of LasMed LLC may not be available for sharing.

Patient-level data will be made available within 6 months after publication of the primary manuscript.

Data will be provided to researchers who submit a methodologically sound research proposal including a protocol and statistical analysis plan. No patient-identifying fields (including dates) will be included in the shared dataset. Certain technical data related to the intellectual property rights of LasMed LLC may not be available for sharing.