Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 28Peripheral Neuropathies and DisordersCancer Treatment and PharmacologyHereditary Neurological Disorders

The DOI matches its Crossref record.

Toxicity in Peripheral Nerves: An Overview

Open access
Grisold, Wolfgang, Carozzi, Valentina·2021·Toxics
DOI 10.3390/toxics9090218PMC PMC8472820
Open this paper in CoChat — free accountOpen PDF

Abstract

Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of substances and by different mechanisms. Toxic agents are numerous and can be distinguished between drugs, recreational agents, heavy metals, industrial agents, pesticides, warfare agents, biologic substances and venoms. Toxic agents reach the nervous system by ingestion, transcutaneously, via the mucous membranes, parenterally and by aerosols. The most frequent types are cumulative toxicities. Other types are acute or delayed toxicities. Pathogenetic mechanisms range from a specific toxic substance profile causing axonal or demyelinating lesions, towards ion channel interferences, immune-mediated mechanisms and a number of different molecular pathways. In addition, demyelination, focal lesions and small fiber damage may occur. Clinically, neurotoxicity presents most frequently as axonal symmetric neuropathies. In this work, we present a panoramic view of toxic neuropathy, in terms of symptoms, causes, mechanisms and classification.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/toxics9090218

Cites

Statistics

Figures

Figure 1 A schematic representation of the time course of toxic neuropathy caused by chemotherapy from exposure and onset of the toxicity on the PNS to the late effects and coasting phenomenon. Variable time course in patients receiving cancer treatment. The figure contains 3 critical time aspects (zones) for the development of chemotherapy-induced neurotoxicity (CIPN): (A): Acute toxicity is less frequent, and can be demonstrated in oxaliplatin toxicity. The acute toxic effects typically occur at the first intervention. (B): Cumulative toxicity, which usually follows the cumulation of the toxic agents’ chemotherapy cycle. Toxicity is usually incrementally increasing (symbolized by the black line). “Late and delayed” as well as intermediate toxicity stand for other patterns, such as immune-induced effects in ICI or intermediate effects caused by OPS. (C): Other late effects. After termination of chemotherapy, symptoms can progress for a variable time and then remit (“Coasting”). The extent of late effects in chemotherapy-induced neuropathies is an important question, as the number of cured patients and long-term survivors increases. In a few instances, such as TCE intoxication and also some OPS, progression after the termination of the exposure has also been described (self-perpetuation).
Figure 1 A schematic representation of the time course of toxic neuropathy caused by chemotherapy from exposure and onset of the toxicity on the PNS to the late effects and coasting phenomenon. Variable time course in patients receiving cancer treatment. The figure contains 3 critical time aspects (zones) for the development of chemotherapy-induced neurotoxicity (CIPN): (A): Acute toxicity is less frequent, and can be demonstrated in oxaliplatin toxicity. The acute toxic effects typically occur at the first intervention. (B): Cumulative toxicity, which usually follows the cumulation of the toxic agents’ chemotherapy cycle. Toxicity is usually incrementally increasing (symbolized by the black line). “Late and delayed” as well as intermediate toxicity stand for other patterns, such as immune-induced effects in ICI or intermediate effects caused by OPS. (C): Other late effects. After termination of chemotherapy, symptoms can progress for a variable time and then remit (“Coasting”). The extent of late effects in chemotherapy-induced neuropathies is an important question, as the number of cured patients and long-term survivors increases. In a few instances, such as TCE intoxication and also some OPS, progression after the termination of the exposure has also been described (self-perpetuation).CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 61

  1. Hill, 1965, The Environment and Disease: Association or Causation?, Proc. R. Soc. Med., 58, 295
  2. Hill, 2015, The environment and disease: Association or causation? 1965, J. R. Soc. Med., 108, 32, 10.1177/0141076814562718 · DOI
  3. Ventura, 2015, Predicting concentrations of cytostatic drugs in sewage effluents and surface waters of Catalonia (NE Spain), Environ. Res., 138, 161, 10.1016/j.envres.2015.02.015 · DOI
  4. Moretti, M., Bonfiglioli, R., Feretti, D., Pavanello, S., Mussi, F., Grollino, M.G., Villarini, M., Barbieri, A., Ceretti, E., and Carrieri, M. (2011). A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: A multicentric project. BMC Public Health, 11. · DOI
  5. Hachisuka, 2018, Itch and neuropathic itch, Pain, 159, 603, 10.1097/j.pain.0000000000001141 · DOI
  6. Oaklander, 2012, Common neuropathic itch syndromes, Acta Derm. Venereol., 92, 118, 10.2340/00015555-1318 · DOI
  7. Saviuc, 2001, Erythromelalgia and mushroom poisoning, J. Toxicol. Clin. Toxicol., 39, 403, 10.1081/CLT-100105162 · DOI
  8. Cimolai, 2009, Erythromelalgia accompanying rosuvastatin-associated myopathy, J. Dermatol. Case Rep., 3, 1, 10.3315/jdcr.2009.1026 · DOI
  9. Grzybowski, 2015, Toxic optic neuropathies: An updated review, Acta Ophthalmol., 93, 402, 10.1111/aos.12515 · DOI
  10. Aghdam, 2017, An Updated Review on the Most Common Agents Causing Toxic Optic Neuropathies, Curr. Pharm. Des., 23, 586, 10.2174/1381612823666170124113826 · DOI
  11. Du, 2019, Aspects of vincristine-induced neuropathy in hematologic malignancies: A systematic review, Cancer Chemother. Pharmacol., 84, 471, 10.1007/s00280-019-03884-5 · DOI
  12. Fehm, 2008, Paravasation von Zytostatika, Der Gynäkologe, 41, 607, 10.1007/s00129-008-2173-1 · DOI
  13. Emre, 2009, Median Nerve Injury Due to High-Pressure Water Jet Injection: A Case Report and Review of Literature, Eur. J. Trauma Emerg. Surg., 35, 411, 10.1007/s00068-008-8092-y · DOI
  14. Busse, 1983, Peripheral nerve damage following isolated extremity perfusion with cis-platinum, Recent Results Cancer Res., 86, 264, 10.1007/978-3-642-82025-0_44 · DOI
  15. Peel, 1990, Localized neuropathy following jellyfish sting, Postgrad. Med J., 66, 953, 10.1136/pgmj.66.781.953 · DOI
  16. Hebl, 2001, Diffuse Brachial Plexopathy after Interscalene Blockade in a Patient Receiving Cisplatin Chemotherapy: The Pharmacologic Double Crush Syndrome, Anesth. Analg., 92, 249, 10.1097/00000539-200101000-00049 · DOI
  17. Novak, 2015, Association of Statins with Sensory and Autonomic Ganglionopathy, Front. Aging Neurosci., 7, 191, 10.3389/fnagi.2015.00191 · DOI
  18. Giannoccaro, 2011, Somatic and autonomic small fiber neuropathy induced by bortezomib therapy: An immunofluorescence study, Neurol. Sci., 32, 361, 10.1007/s10072-010-0475-2 · DOI
  19. Gebremedhn, E.G., Shortland, P.J., and Mahns, D.A. (2018). The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: A systematic review. BMC Cancer, 18. · DOI
  20. Alcaraz, 2002, Intrathecal vincristine: Fatal myeloencephalopathy despite cerebrospinal fluid perfusion, J. Toxicol. Clin. Toxicol., 40, 557, 10.1081/CLT-120014647 · DOI
  21. Otsuka, 2020, Impact of peripheral neuropathy induced by platinum in first-line chemotherapy on second-line chemotherapy with paclitaxel for advanced gastric cancer, Int. J Clin. Oncol., 25, 595, 10.1007/s10147-019-01598-5 · DOI
  22. Cox, 2018, Modernizing the Bradford Hill criteria for assessing causal relationships in observational data, Crit. Rev. Toxicol., 48, 682, 10.1080/10408444.2018.1518404 · DOI
  23. Abdollahi, 2012, A comprehensive review on experimental and clinical findings in intermediate syndrome caused by organophosphate poisoning, Toxicol. Appl. Pharmacol., 258, 309, 10.1016/j.taap.2011.11.014 · DOI
  24. Haliga, 2018, New insights into the organophosphate-induced intermediate syndrome, Arh. Hig. Rada. Toksikol., 69, 191, 10.2478/aiht-2018-69-3121 · DOI
  25. Vasconcellos, 2002, Organophosphate-induced delayed neuropathy: Case report, Arq. Neuropsiquiatr., 60, 1003, 10.1590/S0004-282X2002000600022 · DOI
  26. Agalave, 2021, Neuroimmune Consequences of eIF4E Phosphorylation on Chemotherapy-Induced Peripheral Neuropathy, Front. Immunol., 12, 642420, 10.3389/fimmu.2021.642420 · DOI
  27. Fumagalli, 2021, Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy, Front. Immunol., 11, 626687, 10.3389/fimmu.2020.626687 · DOI
  28. Lehr, 1972, Sulfonamide vasculitis, J. Clin. Pharmacol. New Drugs., 12, 181, 10.1002/j.1552-4604.1972.tb00159.x · DOI
  29. Adjemian, 2009, A clustering of immune-mediated polyradiculoneuropathy among swine abattoir workers exposed to aerosolized porcine brains, Indiana, United States, Int. J. Occup. Environ. Health, 15, 331, 10.1179/oeh.2009.15.4.331 · DOI
  30. Gelpi, 2002, The Spanish toxic oil syndrome 20 years after its onset: A multidisciplinary review of scientific knowledge, Environ. Health Perspect., 110, 457
  31. Grisold, 1984, The syndrome of continuous muscle fibre activity following gold therapy, J. Neurol., 231, 244, 10.1007/BF00313659 · DOI
  32. Jortner, 2000, Mechanisms of toxic injury in the peripheral nervous system: Neuropathologic considerations, Toxicol. Pathol., 28, 54, 10.1177/019262330002800108 · DOI
  33. Kist, A.M., Sagafos, D., Rush, A.M., Neacsu, C., Eberhardt, E., Schmidt, R., Lunden, L.K., Ørstavik, K., Kaluza, L., and Meents, J. (2016). SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing. PLoS ONE, 11. · DOI
  34. Carozzi, 2009, Effect of the chronic combined administration of cisplatin and paclitaxel in a rat model of peripheral neurotoxicity, Eur. J. Cancer, 45, 656, 10.1016/j.ejca.2008.10.038 · DOI
  35. Meregalli, 2021, Blood molecular biomarkers for chemotherapy-induced peripheral neuropathy: From preclinical models to clinical practice, Neurosci. Lett., 749, 135739, 10.1016/j.neulet.2021.135739 · DOI
  36. Benbow, 2016, Effects of Paclitaxel and Eribulin in Mouse Sciatic Nerve: A Microtubule-Based Rationale for the Differential Induction of Chemotherapy-Induced Peripheral Neuropathy, Neurotox. Res., 29, 299, 10.1007/s12640-015-9580-6 · DOI
  37. Smith, 2016, Structural Basis for Induction of Peripheral Neuropathy by Microtubule-Targeting Cancer Drugs, Cancer Res., 76, 5115, 10.1158/0008-5472.CAN-15-3116 · DOI
  38. Herskowitz, 1971, n-Hexane neuropathy: A syndrome occurring as a result of industrial exposure, N. Engl. J. Med., 285, 82, 10.1056/NEJM197107082850204 · DOI
  39. Rizzuto, 1980, n-Hexane polyneuropathy: An occupational disease of shoemakers, Eur. Neurol., 19, 308, 10.1159/000115166 · DOI
  40. Chang, 1990, Patients with n-hexane induced polyneuropathy: A clinical follow up, Br. J. Ind. Med., 47, 485
  41. Huang, 2008, Polyneuropathy induced by n-hexane intoxication in Taiwan, Acta Neurol. Taiwanica, 17, 3
  42. Lee, 1992, Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells, Cell, 68, 451, 10.1016/0092-8674(92)90183-D · DOI · Paper page
  43. Mata, 1992, Phosphorylation-dependent neurofilament epitopes are reduced at the node of Ranvier, J. Neurocytol., 21, 199, 10.1007/BF01194978 · DOI
  44. Hsieh, 1994, Regional modulation of neurofilament organization by myelination in normal axons, J. Neurosci., 14, 6392, 10.1523/JNEUROSCI.14-11-06392.1994 · DOI
  45. Shemesh, 2010, Paclitaxel induces axonal microtubules polareconfiguration and impaired organelle transport: Implications for the pathogenesis of paclitaxel-induced polyneuropathy, Acta Neuropathol., 119, 235, 10.1007/s00401-009-0586-0 · DOI
  46. Yin, 1998, Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons, J. Neurosci., 18, 1953, 10.1523/JNEUROSCI.18-06-01953.1998 · DOI
  47. Cosgaya, 2002, The neurotrophin receptor p75NTR as a positive modulator of myelination, Science, 298, 1245, 10.1126/science.1076595 · DOI · Paper page
  48. Syroid, 1996, Cell death in the Schwann cell lineage and its regulation by neuregulin, Proc. Natl. Acad. Sci. USA, 93, 9229, 10.1073/pnas.93.17.9229 · DOI
  49. Guenard, 1995, Transforming growth factor-beta blocks myelination but not ensheathment of axons by Schwann cells in vitro, J. Neurosci., 15, 419, 10.1523/JNEUROSCI.15-01-00419.1995 · DOI
  50. Towfighi, 1974, Hexachlorophene-induced changes in central and peripheral myelinated axons of developing and adult rats, Lab. Investig., 31, 712
  51. Tripier, 1981, Hexachlorophene and the central nervous system. Toxic effects in mice and baboons, Acta Neuropathol., 53, 65, 10.1007/BF00697186 · DOI
  52. Graham, 1976, Triethyltin sulfateinduced neuropathy in rats. Electrophysiologic, morphologic, and biochemical studies, Arch. Neurol., 33, 40, 10.1001/archneur.1976.00500010042007 · DOI
  53. Hanz, 2006, Retrograde signaling in injured nerve–the axon reaction revisited, J. Neurochem., 99, 13, 10.1111/j.1471-4159.2006.04089.x · DOI
  54. Scheib, 2013, Advances in peripheral nerve regeneration, Nat. Rev. Neurol., 9, 668, 10.1038/nrneurol.2013.227 · DOI · Paper page
  55. Adelsberger, 2000, The chemotherapeutic oxaliplatin alters voltage-gated Na(þ) channel kinetics on rat sensory neurons, Eur. J. Pharmacol., 406, 25, 10.1016/S0014-2999(00)00667-1 · DOI · Paper page
  56. Park, S.B., Lin, C.S.Y., Krishnan, A.V., Goldstein, D., Friedlander, M.L., and Kiernan, M.C. (2011). Dose effects of oxaliplatin on persistent and transient Naþ conductances and the development of neurotoxicity. PLoS ONE, 6. · DOI
  57. Wu, 2009, The mechanism of the actions of oxaliplatin on ion currents and action potentials in differentiated NG108-15 neuronal cells, Neurotoxicology, 30, 677, 10.1016/j.neuro.2009.04.010 · DOI
  58. Webster, 2005, Oxaliplatin induces hyperexcitability at motor and autonomic neuromuscular junctions through effects on voltage-gated sodium channels, Br. J. Pharmacol., 146, 1027, 10.1038/sj.bjp.0706407 · DOI
  59. Quartu, 2014, Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve, Biomed Res. Int., 2014, 180428, 10.1155/2014/180428 · DOI
  60. Warwick, 2013, The contribution of satellite glial cells to chemotherapy-induced neuropathic pain, Eur. J. Pain, 17, 571, 10.1002/j.1532-2149.2012.00219.x · DOI
  61. Ali, 2018, Effectiveness of antiarrhythmic drugs for shockable cardiac arrest: A systematic review, Resuscitation, 132, 63, 10.1016/j.resuscitation.2018.08.025 · DOI

Cited by

See all 28

Metadata

Authors
Grisold, W., & Carozzi, V.
Affiliations
  • Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA (AT)
  • University of Milano-Bicocca (IT)
Corresponding author
Carozzi, Valentina
ORCID
Venue
Toxics
Publisher
MDPI AG
Published
2021-09-11
Volume
9
Issue
9
Pages
218
ISSN
2305-6304 (ISSN-L)
DOI
10.3390/toxics9090218
PMC
PMC8472820
OpenAlex
W3199678217
Cited by
28
References
63
Citations by year
2026: 3 · 2025: 13 · 2024: 3 · 2023: 4 · 2022: 5
FWCI
0.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Toxics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
toxic neuropathy, peripheral nerve toxicity, neurotoxicity, drug-induced neuropathy, heavy metals, pesticides, venom, demyelination, axonal neuropathy, autoimmune neuropathy, cumulative toxicity

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Toxicity in Peripheral Nerves: An Overview. https://app.cochat.ai/papers/10.3390/toxics9090218
The paper
Grisold, W., & Carozzi, V. (2021). Toxicity in Peripheral Nerves: An Overview. Toxics. https://doi.org/10.3390/toxics9090218

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.