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Behavioral and immunohistological assessment of painful neuropathy induced by a single oxaliplatin injection in the rat.
Toxicology. 2007 May 20; 234(3):176-84.T

Abstract

In clinical use, a single infusion of oxaliplatin, widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs triggered or aggravated by exposure to cold. To study the pathophysiology of these symptoms, we developed and characterized an animal model that reproduces the effects of a single intraperitoneal oxaliplatin administration (3, 6 and 12 mg/kg). Significant allodynia and hyperalgesia to cold stimuli were rapidly observed from 24 h to day 5 with a maximum lowering of 76% at t+30 h versus control. Other behavioral assessments revealed rapid persistent mechanical allodynia, but no thermal hyperalgesia or allodynia to heat and no hyperalgesia to mechanical stimuli. An immunohistochemical study in the superficial layers of the spinal dorsal horn revealed a marked increase in substance P immunoreactivity versus controls (12% versus 4%), whereas calcitonin gene-related peptide (CGRP) immunoreactivity was unchanged. This new animal model for the first time closely mimics the effects observed in humans after a single oxaliplatin infusion, especially onset and highly intense sensory disturbances, hypersensitivity to cold with allodynia and hyperalgesia signs. This model may help to elucidate the mechanisms of this thermal hypersensitivity, especially the possible involvement of small-diameter A-fibers in cold allodynia symptoms. These selective effects may clue up the mechanistic basis for the acute oxaliplatin neuropathy leading to a better understanding of the clinical condition and to optimize its treatment.

Authors+Show Affiliations

INSERM U766, F63001 Clermont-Ferrand, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17418472

Citation

Ling, Bing, et al. "Behavioral and Immunohistological Assessment of Painful Neuropathy Induced By a Single Oxaliplatin Injection in the Rat." Toxicology, vol. 234, no. 3, 2007, pp. 176-84.
Ling B, Coudoré-Civiale MA, Balayssac D, et al. Behavioral and immunohistological assessment of painful neuropathy induced by a single oxaliplatin injection in the rat. Toxicology. 2007;234(3):176-84.
Ling, B., Coudoré-Civiale, M. A., Balayssac, D., Eschalier, A., Coudoré, F., & Authier, N. (2007). Behavioral and immunohistological assessment of painful neuropathy induced by a single oxaliplatin injection in the rat. Toxicology, 234(3), 176-84.
Ling B, et al. Behavioral and Immunohistological Assessment of Painful Neuropathy Induced By a Single Oxaliplatin Injection in the Rat. Toxicology. 2007 May 20;234(3):176-84. PubMed PMID: 17418472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioral and immunohistological assessment of painful neuropathy induced by a single oxaliplatin injection in the rat. AU - Ling,Bing, AU - Coudoré-Civiale,Marie-Ange, AU - Balayssac,David, AU - Eschalier,Alain, AU - Coudoré,François, AU - Authier,Nicolas, Y1 - 2007/03/01/ PY - 2007/01/03/received PY - 2007/02/21/revised PY - 2007/02/21/accepted PY - 2007/4/10/pubmed PY - 2007/7/4/medline PY - 2007/4/10/entrez SP - 176 EP - 84 JF - Toxicology JO - Toxicology VL - 234 IS - 3 N2 - In clinical use, a single infusion of oxaliplatin, widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs triggered or aggravated by exposure to cold. To study the pathophysiology of these symptoms, we developed and characterized an animal model that reproduces the effects of a single intraperitoneal oxaliplatin administration (3, 6 and 12 mg/kg). Significant allodynia and hyperalgesia to cold stimuli were rapidly observed from 24 h to day 5 with a maximum lowering of 76% at t+30 h versus control. Other behavioral assessments revealed rapid persistent mechanical allodynia, but no thermal hyperalgesia or allodynia to heat and no hyperalgesia to mechanical stimuli. An immunohistochemical study in the superficial layers of the spinal dorsal horn revealed a marked increase in substance P immunoreactivity versus controls (12% versus 4%), whereas calcitonin gene-related peptide (CGRP) immunoreactivity was unchanged. This new animal model for the first time closely mimics the effects observed in humans after a single oxaliplatin infusion, especially onset and highly intense sensory disturbances, hypersensitivity to cold with allodynia and hyperalgesia signs. This model may help to elucidate the mechanisms of this thermal hypersensitivity, especially the possible involvement of small-diameter A-fibers in cold allodynia symptoms. These selective effects may clue up the mechanistic basis for the acute oxaliplatin neuropathy leading to a better understanding of the clinical condition and to optimize its treatment. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/17418472/Behavioral_and_immunohistological_assessment_of_painful_neuropathy_induced_by_a_single_oxaliplatin_injection_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(07)00105-9 DB - PRIME DP - Unbound Medicine ER -