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Objectives Neurological complications including pain are common after treatment for breast cancer. This prospective study investigated the symptoms, intensity and interference of chemotherapy-induced peripheral neuro-pathy. (CIPN) in the feet and hands compared to surgery- and radiation-induced neuropathy in the breast and upper arm. Methods Consecutive patients referred to surgery for breast cancer were included in a prospective study and completed a questionnaire at baseline and a follow-up questionnaire and interview after one year. CIPN was assessed with the CIPN20 questionnaire and the Michigan Neuropathy Screening Instrument questionnaire (MNSIq). Pain intensity was rated on a numeric rating scale (NRS, 0–10). Results In total 144 patients were included, of which 73 received chemotherapy. At one-year follow-up, symptoms of polyneuropathy were more common in patients treated with chemotherapy. Tingling or numbness in the feet in those treated/not treated with chemotherapy was reported by 44 (62%) and 15 (21%), respectively. Pain was present in 22 (30%) and 10 (14%), respectively. Pain in the area of surgery was reported by 66 (46%). Although less common, pain in the feet in those treated with chemotherapy was rated as more intense and with more daily life interference than pain in the surgical area (NRS 5.5 (SD 1.9) vs. 3.1 (SD 1.9). Conclusions Neurological complications including pain following surgery and chemotherapy represent a burden to breast cancer survivors. In those who had received chemotherapy, pain in the feet was less common than pain in the surgical area, but pain in the feet was more intense and had a higher interference with daily life. Our study emphasizes the need for either baseline data or a control population for improved estimation of the presence and severity of CIPN and pain from questionnaires.

Objective: Axonal excitability reflects ion channel function, and it is proposed that this may be a biomarker in painful (vs painless) polyneuropathy. Our objective was to investigate the relationship between axonal excitability parameters and chronic neuropathic pain in deeply phenotyped cohorts with diabetic or chemotherapy-induced distal symmetrical polyneuropathy. Methods: Two hundred thirty-nine participants with diabetic polyneuropathy were recruited from sites in the UK and Denmark, and 39 participants who developed chemotherapy-induced polyneuropathy were recruited from Denmark. Participants were separated into those with probable or definite neuropathic pain and those without neuropathic pain. Axonal excitability of large myelinated fibers was measured with the threshold tracking technique. The stimulus site was the median nerve, and the recording sites were the index finger (sensory studies) and abductor pollicis brevis muscle (motor studies). Results: Participants with painless and painful polyneuropathy were well matched across clinical variables. Sensory and motor axonal excitability measures, including recovery cycle, threshold electrotonus, strength–duration time constant, and current–threshold relationship, did not show differences between participants with painful and painless diabetic polyneuropathy, and there were only minor changes for chemotherapy-induced polyneuropathy. Interpretation: Axonal excitability did not significantly differ between painful and painless diabetic or chemotherapy-induced polyneuropathy in a multicenter observational study. Threshold tracking assesses the excitability of myelinated axons; the majority of nociceptors are unmyelinated, and although there is some overlap of the "channelome" between these axonal populations, our results suggest that alternative measures such as microneurography are required to understand the relationship between sensory neuron excitability and neuropathic pain. ANN NEUROL 2022;91:506–520.

This chapter presents the case of a man who has cold dysesthesia due to oxaliplatin-induced peripheral neuropathy. Chemotherapy-induced peripheral neuropathy is a daily challenge in cancer patients. Oxaliplatin can cause an acute neuropathy characterized by cold dysesthesia, a chronic neuropathy characterized by a “glove-and-stocking-like” distribution of symptoms (paresthesia, dysesthesia, and pain), and sensory loss. There are no established preventive treatments. In patients with oxaliplatin-induced neuropathy, treatment mainly consists of symptomatic antineuropathic drugs akin to other painful neuropathies, and it should not start with opioids. Patients with chemotherapy-induced neuropathy reporting paresthesia such as numbness or tingling but not pain should not be treated with analgesics.

AIM: Colorectal cancer survivors are one of the most rapidly growing groups of patients living with and beyond cancer. In a national multidisciplinary setting, we have examined the extent of late treatment-related sequelae in colorectal cancer survivors and present the scientific evidence for management of these conditions in this patient category with the aim of facilitating identification and treatment.METHOD: A systematic search for existing guidelines and relevant studies was performed across 16 and 4 databases, respectively, from inception to 2021. This yielded 13 guidelines and 886 abstracts, of which 188 were included in the finalized guideline (231 included for full text review). Secondarily, bibliographies were cross-referenced and 53 additional articles were included.RESULTS: Symptoms have been divided into overall categories including psychosocial, bowel-related, urinary, sexual (male and female), pain/neuropathy and fatigue symptoms or complaints that are examined individually. Merging and grading of data resulted in 22 recommendations and 42 management strategies across categories. Recommendations are of a more general character, whereas management strategies provide more practical advice suited for initiation on site before referral to specialized units.CONCLUSION: Treatment-related sequelae in colorectal cancer survivors are common and attention needs to be focused on identifying patients with unmet treatment needs and the development of evidence-based treatment algorithms.

Objectives Chronic pain is common following cancer treatment. This is a brief discussion of pain assessment after cancer treatment. Methods Summary of a lecure for the SASP (Scandinavian Journal of Pain) annual meeting 2022. Results Assessment of pain involves identifying the presence of pain, its underlying cause, its impact as well as underlying mechanisms. Conclusions Detailed pain assessment is important for the clinic and for epidemiological and mechanistic studies as well as pain treatment studies.

International audience; Neuropathic pain highly affects quality of life, well-being, and function. It has recently been shown based on cluster analysis studies that most patients with neuropathic pain may be categorized into 1 of 3 sensory phenotypes: sensory loss, mechanical hyperalgesia, and thermal hyperalgesia. If these phenotypes reflect underlying pathophysiological mechanisms, they may be more relevant for patient management than underlying neurological diagnosis or pain intensity. The aim of this study was thus to examine the impact of these sensory phenotypes on mental health, functionality, and quality of life. Data of 433 patients from the IMI/EuroPain network database were analyzed, and results of HADS-D/A, Pain Catastrophizing Scale, Euro Quality of Life 5D/-VAS, Brief Pain Inventory, and Graded Chronic Pain Scale between the sensory phenotypes were compared using multiple regression analysis. There was no difference in chronic pain grade, pain intensity, depression, or anxiety scores between phenotypes. Pain interference (Brief Pain Inventory) was higher (P = 0.002); self-reported health state lower (Euro Quality of Life 5D VAS, P = 0.02); and problems regarding mobility (P = 0.008), usual activities (P = 0.004), and self-care (P = 0.039) more prominent (EQ5-D) in the sensory loss compared with the thermal hyperalgesia phenotype. Patients with sensory loss also showed higher pain catastrophizing scores (P = 0.006 and 0.022, respectively) compared with the 2 other groups. Sensory phenotype is associated with the impact of neuropathic pain conditions on well-being, daily functionality, and quality of life but is less associated with pain intensity. These results suggest that the somatosensory phenotype should be considered for personalized pain management. Copyright

The aim of this study was to evaluate the presence and characterization of chemotherapy‐induced neuropathy (CIPN) and neuropathic pain 5 years after adjuvant chemotherapy with docetaxel or oxaliplatin. Patients from an ongoing prospective study, who had received adjuvant chemotherapy with docetaxel or oxaliplatin in 2011 to 2012 were invited to participate. The patients underwent a thorough examination with interview, neurological examination, questionnaires, assessment tools, nerve conduction studies (NCS), quantitative sensory testing, MScan motor unit number estimation (MUNE), and corneal confocal microscopy (CCM). Patients were divided into no, possible, probable, and confirmed CIPN. Out of the 132 eligible patients, 63 agreed to participate: 28 had received docetaxel and 35 had received oxaliplatin. Forty‐one percent had confirmed CIPN, 34% possible or probable CIPN, and 22% did not have CIPN. The CIPN was characterized mainly by sensory nerve fiber loss, with a more pronounced large fiber than small fiber loss but also some motor fiber loss identified on NCS and MUNE. In general, patients had mild neuropathy with relatively low scores on assessment tools and no association with mood and quality of life. CCM was not useful as a diagnostic tool. Of the patients with probable or confirmed CIPN, 30% experienced pain, which was most often mild, but still interfered moderately with daily life in 20% to 25% and was associated with lower quality of life. In conclusion CIPN was confirmed in 41% 5 years after chemotherapy. The neuropathy was generally mild, but in patients with neuropathic pain it was associated with lower quality of life.

Neuropathic pain is a common complication to cancer and cancer treatments, such as surgery, chemotherapy, and radiation therapy. Neuropathic pain may be present in up to 40% of cancer patients and may persist independently of the cancer and affect the quality of life in disease-free cancer survivors. Particular surgery and chemotherapy may cause chronic neuropathic pain in cancer survivors. The diagnosis of neuropathic pain can be challenging and requires documentation of a nervous system lesion and pain in areas of sensory changes. The pharmacological treatment includes tricyclic antidepressants, selective serotonin–noradrenaline reuptake inhibitors (duloxetine or venlafaxine), gabapentin, and pregabalin as first-line treatments. Topical lidocaine 5%, capsaicin 8% patches, botulinum toxin type A, tramadol, and strong opioids are second- and third-line treatments. Steroids may have a role in the acute management of cancer-related neuropathic pain. Due to limited efficacy or intolerable side effects at maximal doses, combination therapy is often required and careful monitoring of effect and adverse reactions is important.

ObjectiveTo test whether contralateral sensory abnormalities in the clinically unaffected area of patients with unilateral neuropathic pain are due to the neuropathy or pain mechanisms.MethodsWe analyzed the contralateral clinically unaffected side of patients with unilateral painful or painless neuropathy (peripheral nerve injury [PNI], postherpetic neuropathy [PHN], radiculopathy) by standardized quantitative sensory testing following a validated protocol. Primary outcome was the independent contribution of the following variables on the contralateral sensory function using generalized linear regression models: pain intensity, disease duration, etiology, body area, and sensory patterns in the most painful area.ResultsAmong 424 patients (PNI n = 256, PHN n = 78, radiculopathy n = 90), contralateral sensory abnormalities were frequent in both painful (n = 383) and painless (n = 41) unilateral neuropathy, demonstrating sensory loss for thermal and mechanical nonpainful stimuli and both sensory loss and gain for painful test stimuli. Analysis by etiology revealed contralateral pinprick hyperalgesia in PHN and PNI. Analysis by ipsilateral sensory phenotype demonstrated mirror-image pinprick hyperalgesia in both mechanical and thermal hyperalgesia phenotypes. Pain intensity, etiology, and affected body region predicted changes in only single contralateral somatosensory parameters. Disease duration had no impact on the contralateral sensory function.ConclusionMechanisms of sensory loss seem to spread to the contralateral side in both painful and painless neuropathies. Contralateral spread of pinprick hyperalgesia was restricted to the 2 ipsilateral phenotypes that suggest sensitization; this suggest a contribution of descending net facilitation from supraspinal areas, which was reported in rodent models of neuropathic pain but not yet in human patients.

Objective In patients with chemotherapy-induced peripheral neuropathy (CIPN), demonstration of small fibre (SF) damage is important to understand chronic late effects. Methods Thirty patients having complaints compatible with possible CIPN following treatment with oxaliplatin or docetaxel were compared with 27 healthy subjects. All subjects were evaluated with quantitative sensory testing (QST) assessing SF function and laser evoked potentials (LEP). In addition, SF-damage was assessed using cutaneous silent periods evoked with electrical (El-CSP) and laser (Ls-CSP) stimuli. Results For LEP, N2P2 amplitudes were significantly smaller in patients than controls in both upper (P = 0.007) and lower extremities (P = 0.002), and the N1 amplitude in upper extremities of patients were significantly smaller than in controls (P = 0.001). SF-QST, LEP, Ls-CSP, and El-CSP were abnormal in 10 (33.3%), 16 (53.3%), 19 (63.3%), and 24 (80%) of CIPN patients, respectively. Conclusions In patients with possible CIPN, El-CSP and Ls-CSP were more often abnormal than LEP and QST. This is probably because El-CSP and Ls-CSP inform mainly about peripheral nociceptive fibres, while LEP and QST inform about peripheral and central nociceptive pathways together. Significance LEP and QST are established methods to detect SF-damage. El- and Ls-CSP might help clinicians in diagnosing SF-damage.

Objective: To determine symptoms and characteristics of chronic sensory neuropathy in patients treated with oxaliplatin and docetaxel, including patterns of somatosensory abnormalities, pain descriptors, and psychological functioning.Design: A retrospective cross-sectional study.Setting: A chronic pain research center.Subjects: Thirty-eight patients with chronic peripheral pain and/or dysesthesia following chemotherapy.Methods: Sensory profiles, psychological functioning, and quality of life were assessed using standardized questionnaires. In addition, standardized quantitative sensory testing and nerve conduction studies were carried out.Results: The sensory profiles and clinical symptoms were very similar in the two groups. Pricking, numbness, and burning were common descriptors in both groups, and the predominant finding was sensory loss to A beta-mediated sensory modalities with decreased mechanical and vibration detection thresholds. A high frequency of abnormalities in thermal sensory limen and the presence of paradoxical heat sensation seem to be sensitive markers of small fiber loss. Both groups had mainly sensory, axonal large fiber or mixed fiber polyneuropathy, which tended to be most severe in the oxaliplatin group.Conclusions: Both oxaliplatin-induced and docetaxel-induced polyneuropathies represent a significant problem that affects the daily life of the patients. Our results, defining the somatosensory phenotype, can improve the understanding of the pathophysiological mechanisms useful for future studies in the tailored treatment of prevention of chemotherapy-induced peripheral neuropathy and pain.

Background Following oxaliplatin treatment, acute neurotoxicity symptoms are suggested to be correlated with both the development and degree of chronic neuropathy. Aims The aim of this clinical commentary was to examine different methods to assess acute cold allodynia and dysesthesia in patients treated with adjuvant oxaliplatin. Methods Nine patients over the age of 18 years scheduled for standard adjuvant treatment with capecitabine and oxaliplatin were included. Patients were asked to come for two visits: a baseline visit before and a follow-up visit within 5 days after treatment. Patients were examined with questionnaires, thermal tests, and the thermal grill. Results All patients reported neurotoxicity, and they all had abnormal cold sensitivity. The only significant changes observed were increased ratings of pain, unpleasantness, and pricking sensations to holding a ~8°C metal cylinder for 10 s and an increased intensity of unpleasantness and pricking sensation to the 20-s contact with the 10°C plates of the thermal grill on the palmar hand. Conclusions he results showed that the palm of the hand is the most sensitive part of the body when detecting oxaliplatin-induced cold allodynia, and the use of a cold metal cylinder seems as a promising sensitive method.

OBJECTIVE: Neurotoxicity is the most frequent dose-limiting side effect of the anti-cancer agent oxaliplatin, but the mechanisms are not well understood. This study used nerve excitability testing to investigate the pathophysiology of the acute neurotoxicity. METHODS: Questionnaires, quantitative sensory tests, nerve conduction studies and nerve excitability testing were undertaken in 12 patients with high-risk colorectal cancer treated with adjuvant oxaliplatin and in 16 sex- and age-matched healthy controls. Examinations were performed twice for patients: once within 3 days after oxaliplatin treatment (post-infusion examination) and once shortly before the following treatment (recovery examination). RESULTS: The most frequent post-infusion symptoms were tingling paresthesias and cold allodynia. The most prominent nerve excitability change was decreased superexcitability of motor axons which correlated with the average intensity of abnormal sensations (Spearman Rho = 0.80, p

Background Adjuvant chemotherapy with docetaxel and oxaliplatin increases survival in patients with high-risk breast and colorectal cancer, respectively, but may induce acute and chronic neurotoxicity. This study is a 5-year follow-up of chronic chemotherapy-induced peripheral neuropathy (CIPN). Methods In 2011–2012, 74 patients with high-risk colorectal cancer and 100 patients with high-risk breast cancer answered a questionnaire before, during and one year after receiving adjuvant chemotherapy with oxaliplatin and docetaxel, respectively. In 2016, a 5-year follow-up with the same questionnaire was performed in survivors. Results Fifty-two (36.5% women) of 74 patients (91%) treated with oxaliplatin and 80 (100% women) of 100 patients (85%) treated with docetaxel answered the questionnaire. The most common symptoms of CIPN were tingling in the hands (44.2% in the oxaliplatin (CI 95% 30.5; 58.7) and 36.3% in the docetaxel group (CI 95% 25.8; 47.8)) and feet (52.0% in the oxaliplatin (CI 95% 37.6; 66.0) and 37.5% (CI 95% 29.9; 49.0) in the docetaxel group) and numbness in the feet (34.6% in the oxaliplatin (CI 95% 22.0; 49.1) and 17.5% (CI 95% 9.9; 27.6) in the docetaxel group). Pain was present in the hands or feet in 28.9% of patients treated with oxaliplatin (CI 95% 17.12; 43.0) and 31.3% of patients treated with docetaxel (CI 95% 21.3; 42.6). Conclusions The results showed no major change in symptoms of neuropathy or pain from 1 to 5 years after chemotherapy. Symptoms of neuropathy were more common in patients treated with oxaliplatin.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy. This study evaluates symptoms of CIPN and CIPN-related pain and its influence on psychological functioning as well as potential predictors of chronic CIPN and pain. In this large prospective questionnaire study, 174 patients receiving adjuvant oxaliplatin or docetaxel were consecutively included. Patients were asked to complete a questionnaire with validated questions on peripheral neuropathy, pain, anxiety and depression, and quality of life at baseline, after the first cycle, halfway through therapy, and 1 year after baseline. Chronic CIPN symptoms (tingling and/or numbness) in the feet at 1-year follow-up were present in 63.6% of patients without pre-existing neuropathy in the oxaliplatin group and in 44.8% in the docetaxel group, while pain in hands and feet was found in 31.3% and 35.1%, respectively. The 2 groups had significantly different pain profiles, and persistent pain in the docetaxel group was found to have effect on psychological function. Cumulative dose predicted oxaliplatin-induced neuropathy (P = 0.004), whereas endocrine therapy predicted peripheral pain in the docetaxel group (P = 0.04). There are important differences in acute neuropathy symptoms and chronic pain profiles in patients following oxaliplatin and docetaxel treatment. It is, however, important to recognize that chronic peripheral pain may be unrelated to neuropathy and can be caused by concomitant treatments. Future studies should focus on characterizing and distinguishing CIPN-related pain from other types of pain in order to determine the best outcome measures for trials on prevention or relief.

Objectives Laser evoked potentials (LEPs) have shown less sensitive results than other tests (e.g., skin biopsies, quantitative sensory testing) in diagnosing small fiber neuropathy (SFN), probably because both central and peripheral nociceptive pathways are assessed. Alternatively, laser evoked cutaneous silent period (Ls-CSP) could selectively evaluate peripheral nociceptive pathways only. Methods Thirty patients with chemotherapy-induced chronic pain and/or dysesthesia were compared with 27 healthy subjects. LEPs were recorded from scalp and Ls-CSPs from the abductor pollicis brevis (APB) muscle following random Neodymium-doped yttrium aluminum perovskite (Nd:YAP) laser stimuli given on hairy skin of the extremities. Results For LEPs, mean values of N1 amplitude in upper extremities (8.6 ± 5.4 vs 12.7 ± 5.2 μ V) and N2P2-amplitudes in upper ( 27.9 ± 17.0 vs 35.8 ± 9.6 μ V) and lower extremities (14.5 ± 11.2 vs 24.4 ± 7.7 μ V) were significantly lower in patients than controls ( p 0.01 ). Ls-CSPs were not reproducible in lower extremities. In 18 patients, Ls-CSPs from APB muscle were not recorded. In the rest of the patients ( n = 12), Ls-CSP latencies (139.9 ± 12.4 vs. 131.9 ± 13.7 ms) and durations (19.8 ± 1.4 vs 18.5 ± 1.3 ms) were not different from controls ( p > 0.05 ). Overall, LEPs and Ls-CSPs were abnormal in 16 (53.3%) and 19 (63.3%) patients, respectively. Discussion Ls-CSPs in upper extremities defined more patients than LEPs in upper and lower extremities. Conclusions Ls-CSPs in hands were more sensitive than LEPs in detecting patients with SFN. Significance Ls-CSP could be a useful supplementary test in the diagnosis of SFN, especially in cases with subtle LEP changes.

Objective Nerve conduction studies have limited diagnostic power to assess A δ and C fibers in patients with mixed (large and small fibre neuropathy together) neuropathy, and no power to diagnose small fiber neuropathy (SFN). An option to assess small fibers using standard electro-diagnostic equipment could be cutaneous silent period (CSP) recordings. Methods Thirty patients with chronic pain and/or dysesthesia due to chemotherapy were compared with 27 healthy subjects. Electrical stimulation (25 mA × 1 ms) was delivered on median-sensory and sural nerves. CSPs were recorded from abductor pollicis brevis (APB) and anterior tibial (TA) muscles. In addition, a derived parameter, silent period ratio (SPR), was used to assess A δ functions. The yields of the tests were compared with laser evoked potentials (LEPs) from upper and lower extremities. Results Latencies of APB-CSP and TA-CSP were not significantly different (p > 0.05) between groups. On the other hand, mean APB-CSP duration was longer (32.5 ± 12.6 vs 27.4 ± 9.2 ms, p = 0.004), mean TA-CSP duration shorter (11.8 ± 12.7 vs 39.9 ± 11.6 ms, p Discussion CSP and SPR revealed comparable results with LEPs (16 patients, 53.3%) to define the patients with SFN. Conclusions CSP and SPR could be used to assess peripheral A δ functions. Significance CSPs could be an option to diagnose SFN in the laboratories having only standard electro-diagnostic equipment.

Periphere Neuropathien treten leider nach Chemotherapien regelmasig auf. Ventzel et al. aus Danemark evaluierten nun die Symptome dieser toxischen Polyneuropathie (PNP) und damit assoziierter Schmerzsyndrome sowie deren Auswirkungen auf die psychische Funktionalitat abhangig vom verwendeten Agens. Dabei untersuchten sie auch den Einfluss potenzieller Pradiktoren fur PNP und PNP-assoziierte Schmerzen.

Background Neuropathic pain is usually treated with antidepressants and anticonvulsant. The use of systemic treatment is, however, limited due to poor tolerability and low efficacy. Qutenza, a topical capsaicin patch (8%), is a relatively new treatment for patients with peripheral neuropathic pain (PNP) conditions. The indication for using topical capsaicin treatment is peripheral neuropathic pain in patients without diabetes. Aim To describe the use of topical capsaicin treatment in a pain clinic in patients with PNP. Methods Case series of patients in a neuropathic pain clinic. Results Since October 2010, 40 patients with PNP with different aetiologies have been treated with topical capsaicin; 14 patients had nerve injuries in feet or lower leg or polyneuropathy, 13 patients had nerve lesions related to fingers, hands or arms, seven patients had pain after thoracotomy, four patients postherpetic neuralgia, and two patients had other lesions. Almost half of the patients (47%) were responders and achieved a decrease in pain intensity as well as increased their quality of life (QoL). Responders received 1–6 treatments with capsaicin. Most responders were found in the post-thoracotomy group, of which 86% had a clinical significant reduction in pain. In the group with injuries to the hands, fingers and arms, 46% experienced a reduction in pain. Only 23% of patients with PNP in the feet and lower leg were responders; these patients had a clinical significant increase in QoL. Conclusion In 40 patients with PNP who were treated with topical capsaicin, we found an increase in QoL and a decrease in mean pain intensity of 3 measured on a VAS scale (0–10) in 47% of the treated patients.

Introduction: Cold allodynia is often seen in the acute phase of oxaliplatin treatment, but the underlying pathophysiology remains unclear. Methods: Patients scheduled for adjuvant oxaliplatin for colorectal cancer were examined with quantitative sensory testing and nerve excitability tests at baseline and after the second or third oxaliplatin cycle at different skin temperatures. Results: Seven patients were eligible for examination. All patients felt evoked pain and tingling when touching something cold after oxaliplatin infusion. Oxaliplatin decreased motor nerve superexcitability (P