Premium
May a sigma‐1 antagonist improve neuropathic signs induced by cisplatin and vincristine in rats?
Author(s) -
Paniagua Nancy,
Goicoechea Carlos,
Abalo Raquel,
LópezMiranda Visitacion,
Vela J. Miguel,
Merlos Manuel,
Martín Fontelles María Isabel,
Girón Rocio
Publication year - 2019
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1333
Subject(s) - medicine , neuropathic pain , vincristine , pharmacology , anesthesia , allodynia , antagonist , nociception , peripheral neuropathy , cisplatin , hyperalgesia , chemotherapy , endocrinology , receptor , cyclophosphamide , diabetes mellitus
Abstract Background The antineoplastic drugs cisplatin and vincristine induce peripheral neuropathies. The sigma‐1 receptor (σ1R) is expressed in areas of pain control, and its blockade with the novel selective antagonist MR ‐309 has shown efficacy in nociceptive and neuropathic pain models. Our goal was to test whether this compound reduces neuropathic signs provoked by these antitumoural drugs. Methods Rats were treated with cisplatin or vincristine to induce neuropathies. The effects of acute or repeated administration of MR ‐309 were tested on mechanical and thermal sensitivity, electrophysiological activity of Aδ‐primary afferents in the rat skin–saphenous nerve preparation, and gastrointestinal or cardiovascular functions. Results Rats treated with antitumourals developed tactile allodynia, while those treated with vincristine also developed mechanical hyperalgesia. These in vivo modifications correlated with electrophysiological hyperactivity (increased spontaneous activity and hyperresponsiveness to innocuous and noxious mechanical stimulation). Animals treated with cisplatin showed gastrointestinal impairment and those receiving vincristine showed cardiovascular toxicity. A single dose of MR ‐309 strongly reduced both nociceptive behaviour and electrophysiological changes. Moreover, its concomitant administration with the antitumourals blocked the development of neuropathic symptoms, thus restoring mechanical sensitivity, improving the impairment of feeding behaviour and gastrointestinal transit in the cisplatin‐treated group along with ameliorating the altered vascular reactivity recorded in rats treated with vincristine. Conclusion σ1R antagonist, MR ‐309, reduces sensorial and electrophysiological neuropathic signs in rats treated with cisplatin or vincristine and, in addition, reduces gastrointestinal and cardiovascular side effects. Significance σ1R antagonism could be an interesting and new option to palliate antitumoural neuropathies.