Efficacy assessment of salicylidene salicylhydrazide in chemotherapy associated peripheral neuropathy

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is an increasingly important problem for cancer survivors and is the foremost cause of drug-induced morbidity. In this study, the antinociceptive efficacy of salicylidene salicylhydrazide (SSH) in CIPN was investigated. SSH was evaluated for acute toxicity, antinociceptive effectiveness against tonic and phasic pain modalities, anti-inflammatory propensity, and effect on motoric balance. SSH was tested in the mouse models of oxaliplatin, paclitaxel, and vincristine associated established neuropathic nociceptive paradigms. The tested doses of SSH (10-75 mg/kg) strongly suppressed the expression of acetic acid-induced tonic visceral nociception, formalin-induced biphasic nociception, and acute phasic thermal nociception. SSH selectively antagonized the capsaicin-elicited nociceptive behavior. SSH produced a significant reduction in the phlogistic agents-induced temporal inflammatory escalation involving prostaglandins, serotonin, and histamine. SSH was devoid of any adverse-effects that impair the neurological processes involved in the arousal and coordination of movements. The neuropathic nociception inflicted by chemotherapeutic agents were expressed as reduced sensitivity to non-noxious mechanical stimuli (mechanical allodynia), increased nociceptive response to cold (cold allodynia), and decreased nociceptive latency to heat (heat hyperalgesia). SSH (50 and 75 mg/kg) significantly suppressed the expression of CIPN-induced established neuropathic allodynia and hyperalgesia and the anti-neuropathic effects were equipotent to gabapentin. These findings concluded that SSH is a novel analgesic that can be useful for treating peripheral neuropathic pain conditions linked with chemotherapy with the advantage of being free of neurological adverse-effects encountered with gabapentinoids.

Keywords: Allodynia; Analgesic; Anticancer; Chemotherapy-induced neuropathy; Hyperalgesia; Neuropathic pain; Salicylidene salicylhydrazide (PubChem CID: 135484660).