A rat model of FOLFOX-induced neuropathy: effects of oral dimiracetam in comparison with duloxetine and pregabalin

Abstract

Results FOLFOX reduced the pain threshold in response to mechanical noxious and thermal (cold) non-noxious stimuli beginning from day 14 up to day 42 comparably to oxaliplatin alone. A fifth FOLFOX injection enhanced the severity but not the duration of painful alterations. Spontaneous activity, behavioural, autonomic, and neurological functions were also affected, whereas the motor coordination was not altered. On day 22, duloxetine (15 mg kg −1 , per os), morphine (10 mg kg −1 , subcutaneously), or pregabalin (20 mg kg −1 , per os), acutely administered, reduced the FOLFOX-dependent hypersensitivity. Repeated treatments with dimiracetam (150 mg kg −1 , per os, twice daily, from day 22) significantly protected rats from FOLFOX-induced alterations of pain threshold as well as from autonomic and neurological impairments taking effect after 7 days treatment. Pregabalin repeatedly administered (20 mg kg −1 , per os, twice daily, from day 22) was less effective in reducing mechanical hypersensitivity. Conclusion A clinically consistent model of FOL-FOX-induced neurotoxicity has been developed in rats. Dimiracetam fully reduced hypersensitivity and neurological alterations showing a relevant profile as anti-neuropathic resource.

Intra-Articular Route for the System of Molecules 14G1862 from Centella asiatica: Pain Relieving and Protective Effects in a Rat Model of Osteoarthritis

“…The integrity of motor coordination was assessed based on the number of falls from the rod for a maximum of 600 s. After a maximum of six falls from the rod, the test was suspended and the time was recorded. Each rat was assessed once, and the group mean average score was calculated [31].…”

The active second-generation proteasome inhibitor oprozomib reverts the oxaliplatin-induced neuropathy symptoms

“…The integrity of motor coordination was assessed on the basis of the time the animals kept their balance on the rotating rod for a maximum of 10 min (600 s). After a maximum of 6 falls from the rod, the test was suspended and the time elapsed was recorded [46].…”

Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice

“…Nevertheless, lack of pain-reducing effects has also been reported for non-selective blockers gabapentin and pregabalin (de Andrade et al, 2017;Wiffen et al, 2017). In rodent models of oxaliplatin, T-type, L-type, and non-selective blockers reduce mechanical and/or cold hyperalgesia (Ling et al, 2008;Gauchan et al, 2009;Kawashiri et al, 2012;Aoki et al, 2014;Ohsawa et al, 2014;Ruyang et al, 2015;Di Cesare Mannelli et al, 2017;Sekiguchi et al, 2018). Moreover, in vitro pre-treatment of oxaliplatin for 24 h selectively up-regulates T-and L-type calcium channels in DRG neurons (Schmitt et al, 2018).…”