THE EFFECT OF DEXTROMETHORPHAN,
GABAPENTIN, AMITRIPTYLINE AND
TRAMADOL ON A MOUSE MODEL OF
VINCRISTINE - INDUCED PERIPHERAL
CRISTINA ELENA ZBÂRCEA, SIMONA NEGREŞ*, AURELIA
NICOLETA CRISTEA, CORNEL CHIRIŢĂ
“Carol Davila” University of Medicine and Pharmacy, Faculty of
Pharmacy, Pharmacology and Clinical Pharmacy Department, Traian
Vuia 6, Sect. 2, 020956, Bucharest, Romania
*corresponding author: firstname.lastname@example.org
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Painful peripheral neuropathy is a common side effect of cancer chemotherapy.
In some cases, the pain diminishes within days or weeks after treatment, while in other cases is long-lasting. Since several different mechanisms are supposed to be involved in neuropathic pain, we evaluated the effect of dextromethorphan, gabapentin, amitriptyline and tramadol on vincristine-induced peripheral neuropathy. In the experiment we used adult
male NMRI mice (25 – 35 g; N = 72) divided in six groups: control group (C), vincristine group (VCR), dextromethorphan and vincristine group (DMV), gabapentine and vincristine group (GBV), amitriptyline and vincristine group (AMV), tramadol and vincristine group (TRV). Vincristine (100 μg/kg-bw) was administered intraperitoneally daily for 11 days.
Dextromethorpan (20 mg/kg-bw), gabapentin (150 mg/kg-bw), amitriptyline (25 mg/kgbw) and tramadol (5 mg/kg-bw) were orally administered 11 days concomitantly with vincristine. The thermal sensitivity was evaluated in the 7th and 11th post-treatment days.
We recorded the nociceptive reaction latencies in response to a given thermal stimulus 380C (thermal allodynia) and 520C (thermal hyperalgesia) using the hot plate test (Ugo Basile Hot Plate). No thermal allodynia was observed. On day 7 a statistically significant reduction of the nociceptive reaction latencies was observed on VCR group 5.74 ± 1.72 s.
(p< 0.001), GBV group 6.32 ± 1.79 s. (p< 0.001), and AMV group 6.13 ± 2.25 s. (p< 0.005). Tramadol produced a statistically significant increase of nociceptive reaction latencies with 22.52 % (p< 0.05) compared to VCR group. These results show that tramadol, that has a double mechanism of action: it binds with a low affinity to μ-opioid receptors, and it activates central monoaminergic pathways inhibiting the neuronal uptake of serotonin and noradrenalin, is highly effective to reverse neuropathic hyperalgesia produced by vincristine to mice in the hot plate test.