as affecting sensation in the feet first, then in the hands and fingers. if a patient experiences such abnormalities in sensation, then cipn should be suspected. furthermore, most cipn symptoms appear during the first two months of treatment, progress during treatment, and stabilize after completion. it would be unexpected for cipn to first appear weeks or months after the last dose of chemotherapy treatment. in cipn, sudomotor function, through elctrochemical skin conductance allows for an objective quantification of small fiber impairment and is easy to implement in the clinic. treatment and prevention prevention a 2020 american society of clinical oncology (asco) report provided an updated list of drugs tested and not recommended for prevention of cipn. these recommendations are evidence-based, informed by randomized trials, and guided by expert clinical experience. acetyl-l-carnitine all-trans retinoic acid amifostine amitriptyline calcium magnesium cannabinoids diethyldithiocarbamate glutamate/glutamine glutathione metformin minocycline n-acetylcysteine nimodipine omega-3 fatty acids org 2766 oxcarbazepine retinoic acid venlafaxine vitamin b vitamin e treatment a 2020 asco report provided an updated list of drugs tested and not recommended for treatment of cipn. these recommendations are evidence-based, informed by randomized trials, and guided by expert clinical experience. gabapentin/pregabalin tricyclic antidepressants baclofen ketamine amitriptyline oral cannabinoids as of 2020, duloxetine is the only drug that is currently recommended to treat established cipn. there are data from various clinical trials demonstrating that duloxetine decreases cipn pain and other cipn symptoms. however, it does not eliminate cipn symptoms, and it can also have unwanted side effects such as dizziness, dry mouth, constipation, and diarrhea. it is not approved by the food and drug association for treatment of cipn. behavioral there are promising and safe behavioral interventions for cipn that have been suggested to be helpful based on randomized clinical trials: 1) stretching 2) walking 3) resistance (strength) training 4) balance exercises 5) yoga 6) meditation. stretching, including nerve-gliding, is frequently included in a cipn treatment plan to improve nerve excursion across joints, promote axoplasmic flow, and decrease inflammation. examples of stretching exercises for the neck and upper limbs include shoulder rolls, overhead arm reaches, and arm extensions. examples of stretches for the lower body include lunges and hamstring pulls. stretches like these have been clinically shown to help alleviate pain and restore at least some mobility in patients with cipn. walking can be effective in alleviating cipn symptoms by boosting muscle power, increasing blood circulation, and improving balance. walking provides low to moderately intense aerobic exercise (60-85% of heart rate reserve), and a regular walking schedule can decrease intensity and frequency of neuropathic symptoms while promoting healthy nerve growth and function. resistance (strength) training has been tested in various clinical settings, and it has been shown to be helpful in treating cipn symptoms such as temperature sensitivity, numbness, and tingling. by building muscle, strength training can improve a patient's ability to perform daily activities, improve balance, and reduce the risk of falling. examples of strength training exercises include squats, overhead press, and calf raises. balance exercises, such as tightrope exercises and hip flexion, are shown to be effective in reducing pain and improving quality of life for patients with cipn. they are important in enhancing a patient's proprioception, coordination, and preventing falls. somatic yoga is often used by cancer survivors for symptom management, and it has been found to improve physical and mental health for patients with cipn. yoga combines movement, breathing exercises, and meditation to foster connection between the mind and body. practice may decrease pain-associated stress and help a patient relax through modulation of the neuroendocrine system through the hypothalamic-pituitary-adrenal axis. yoga's emphasis on dynamic movement can lead to improvement in flexibility, strength, balance, and stability, all of which may be negatively impacted by cipn. meditation helps to alleviate cipn symptoms and cipn-related stress by helping a patient relax and improve attention skills. by improving self-control and attention span, mediation helps to create emotional stability and enhances psycho-emotional balance. despite the potential of these interventions, none of them have been shown to definitively help with cipn as of the 2020 asco report. and therefore more research is needed. other therapeutics cryotherapy for patients with cipn involves wearing frozen gloves and socks or ice packs to prevent and relieve symptoms. various studies have been conducted to trial cryotherapy or cryocompression therapy, and their results are largely inconclusive. one study demonstrated that the development of cipn symptoms were significantly delayed after the usage of cryotherapy. another concluded that there was no significant difference between control groups receiving chemotherapy and treatment groups receiving cryotherapy in addition to chemotherapy. the second study's results did, however, support that frozen gloves improved some measures of patient-reported quality-of-life. similarly, compression therapy for patients with cipn involves placing limbs in tight gloves or shoes. studies testing compression therapy reported that sensory neuropathy was reduced in patients using tight surgical gloves. these studies are not conclusive, and additional randomized trials investigating the efficacy of cryotherapy and compression therapy for prevention and treatment of cipn are ongoing. no conclusive recommendations about either therapy can be made as of 2020, although the potential harms of both are believed to be low to moderate. scrambler therapy is an electro-analgesia therapy that is designed to block the conduction of nerve fibers to produce an analgesic effect through transcutaneous electrical nerve stimulation (tens). in other words, this therapy should interfere with (“scramble”) the pain signal transmission of neurons by replacing it with “non-pain” information. one randomized trial evaluating the success of scrambler therapy in alleviating cipn symptoms found no significant differences between treatment and control groups (smith et al. 2020). another trial testing scrambler therapy with patients with cipn found patient-reported neuropathy symptoms and quality-of-life to be improved from baseline status. as of 2020, no conclusive recommendations can be made for scrambler therapy, but its potential harm is believed to be low. current research various institutions, universities, and organizations have dedicated years to performing clinical trials and conducting research on cipn. the scientific community has had multiple breakthroughs in the mechanisms, prevention, and treatment of cipn. in 2017, the national cancer institute's symptom management and health-related quality of life steering committee convened a meeting of cipn and oncology management experts in the clinical trials planning meeting to evaluate the state of current research and plan ahead for future investigation. the goals of the meeting included identification of optimal outcome measures to define the cipn phenotype, establishment of parameters that guide the evaluation of clinically meaningful effects, the adoption of approaches for inclusion of translational and biomarker and/or genetic measures, and discussion of the next steps to implement ideas into future clinical trials. some of the lessons and limitations they learned from conducting past cipn research are that 1) there was insufficient collaboration between pre-clinical and clinical researchers 2) patient reported cipn symptoms are more sensitive than clinician-based assessments 3) there is substantial heterogeneity in the forms of neuropathy manifested across different patients 4) there are promising and understudied behavioral interventions for cipn that may appeal more to patients who do not want pharmacological treatments. based on these lessons, the experts concluded that a multifaceted approach is needed to alleviate the burden of cipn including more well-planned phase ii intervention clinical trials, more longitudinal studies on the risk factors of cipn, and the development of research networks to connect work from different research facilities. overall, more research is needed to advance understanding of cipn etiology, risk assessment, development, and treatment (e.g. duloxetine, genetic targets, and exercise).