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.