Sex-related differences in oxaliplatin-induced changes in the expression of transient receptor potential channels and their contribution to cold hypersensitivity

Miguel, Constanza Ágata; Noya-Riobó, María Victoria; Brumovsky, Pablo Rodolfo; Villar, Marcelo J.; Coronel, Marı́a Florencia

doi:10.1016/j.neulet.2022.136863

Cited by 3 publications

(1 citation statement)

References 55 publications

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“…Oxaliplatin-induced cold allodynia was partly involved with high expression of TRP melastatin 8 (TRPM8) in the primary afferents ( Gauchan et al, 2009 ; Mizoguchi et al, 2016 ). Further animal experiments showed that oxaliplatin produced a distinct increase of TRPV1, TRPM8, and TRPA1 expression in the lumbar DRG ( Chukyo et al, 2018 ; Miguel et al, 2022 ).…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies

et al. 2023

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Oxaliplatin-based chemotherapy is a standard treatment approach for colorectal cancer (CRC). However, oxaliplatin-induced peripheral neurotoxicity (OIPN) is a severe dose-limiting clinical problem that might lead to treatment interruption. This neuropathy may be reversible after treatment discontinuation. Its complicated mechanisms are related to DNA damage, dysfunction of voltage-gated ion channels, neuroinflammation, transporters, oxidative stress, and mitochondrial dysfunction, etc. Several strategies have been proposed to diminish OIPN without compromising the efficacy of adjuvant therapy, namely, combination with chemoprotectants (such as glutathione, Ca/Mg, ibudilast, duloxetine, etc.), chronomodulated infusion, dose reduction, reintroduction of oxaliplatin and topical administration [hepatic arterial infusion chemotherapy (HAIC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), and hyperthermic intraperitoneal chemotherapy (HIPEC)]. This article provides recent updates related to the potential mechanisms, therapeutic strategies in treatment of OIPN, and pharmacokinetics of several methods of oxaliplatin administration in clinical trials.

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Section: Molecular Mechanismsmentioning

confidence: 99%

Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies

et al. 2023

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Pharmacological agents targeting transient receptor potential (TRP) channels in neuropathic pain: Preclinical and clinical status

Dangi,

Sharma

2024

European Journal of Pharmacology

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α9-Containing Nicotinic Acetylcholine Receptors Are Required for RgIA-5474 Attenuation of Chemotherapy-Induced Neuropathic Pain

Azam,

Christensen,

Riaz

et al. 2024

ACS Pharmacol. Transl. Sci.

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Nicotinic acetylcholine receptors containing the α9 subunit have been mechanistically implicated in alleviating chemotherapy-induced neuropathic pain. However, the cell types that underlie these effects are currently unknown. RgIA-5474 is a recently developed, synthetic α-conotoxin analog that is a potent antagonist of human α9α10 nAChRs. We used germline α9 subunit knockout mice, CD3+ T-cell depletion, and conditional knockdown of the α9 subunit in immune cells to examine the role of α9containing nAChRs that mediate RgIA-5474 alleviation of oxaliplatin-induced neuropathic pain. RgIA-5474 potently and selectively blocked mouse α9α10 nAChRs. A one-time oxaliplatin injection resulted in cold allodynia that was reversed by RgIA-5474 administration in the wild type but not in α9 germline knockout mice. RgIA-5474 also failed to produce analgesia in CD3+ T-celldepleted male and female animals. Conditional knockdown of the α9 subunit in immune cells of mice by the CreloxP system also eliminated the therapeutic effects of RgIA-5474 in both male and female mice. These results indicate that the α9 nAChR subunit is necessary for the analgesic effects of RgIA-5474 and implicate α9-containing nAChRs in immune cells as a nonopioid target for treating neuropathic pain.

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Sex-related differences in oxaliplatin-induced changes in the expression of transient receptor potential channels and their contribution to cold hypersensitivity

Cited by 3 publications

References 55 publications

Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies

Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies

Pharmacological agents targeting transient receptor potential (TRP) channels in neuropathic pain: Preclinical and clinical status

α9-Containing Nicotinic Acetylcholine Receptors Are Required for RgIA-5474 Attenuation of Chemotherapy-Induced Neuropathic Pain

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