Single versus repeated administrations of disulfiram on nociception and visceral pain in mice

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC258

Poster Communications: Single versus repeated administrations of disulfiram on nociception and visceral pain in mice

A. Luca3,2, T. Alexa3,2, A. Dondas2, M. M. Leon2, B. I. Tamba2, C. R. Bohotin1,2

1. General and Oromaxillo-Facial Pathology, UMF Gr.T. Popa Iasi, Iasi, Romania. 2. Centre for the Therapy and Study of Pain, UMF Gr.T. Popa Iasi, Iasi, Romania. 3. Physiopathology, UMF Gr.T. Popa Iasi, Iasi, Romania.

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Disulfiram (Dis) is widely used in the treatment of alcoholism (1), also it has been reported that disulfiram changes perception on some tests involving thermonociception (2) and also induces mitochondrial changes through at least two mechanisms (3). The purpose of our study was to assess the effect of a single Dis dose versus repeated administrations (19 days) on thermonociception and visceral pain in mice. Thermonociception was evaluated by hot plate (HPT) and tail flick (TFT) tests and visceral pain by the writhing test. Methods: BALB/c mice (n=62) were divided into 2 groups AG (n=32) receiving a single dose of Dis (50 mg/kgc) by gavage or an equivalent volume of olive oil and CG(n=32) with daily administrations for 19 days of Dis (50 mg/kgc) or same volume olive oil by gavage. The AG was evaluated prior and timely until 240 minutes after administration of Dis or olive oil, the writhing tests was assessed 1h after administration of Dis(n=8) or olive oil (n=8). In CG, after baseline determination, thermonociception was evaluated every 2 days for the next 19 days by HPT and TFT. In the 19th day, writhing tests was performed one hour after the daily administration both for Dis (n=8) and control group (n=8). The maximum possible effect was expressed as [MPE(%)=(treated -baseline)×100/(cut-off – baseline)], where the cut-off for TFT was set at 12s and for HPT at 15s. ANOVA test was used for statistical analysis. Results: On HPT, a single administration showed analgesic effect after one hour and persisted throught the experiment with the MPE at 240 min (MPE= 39.84+/-24.87,p<0.01), on tail-flick a decrease in response time was noted with significance after the first hour (p<0.05).In the writhing test there was a decrease in the number of writhes with no statistical significance. In the CG, on HPT changes were noted from day 9 showing an antinociceptive effect (p=0.02) maintaining until the last day. No significant changes were noted on TFT or in the number of writhes compared with control. Conclusions:Our data demonstrate that both acute and chronic Dis administrations impair thermonociception but have no effect on the visceral pain. One interesting finding is that only one dose has an analgesic effect on HPT while cumulative doses reverse this effect into a persistent hyperalgesia after 3 days of treatment. On the TFT, single or repeated doses of disulfiram produced hyperalgesia. Even further biochemical studies must to be conducted to clarify the mechanism of action we could suppose that transitory/permanent disruption of mitochondrial aldehyde dehydrogenase as well as impairment of norepinephrine release after acute and chronic disulfiram administration are responsible for thermonocicetion changes.



Where applicable, experiments conform with Society ethical requirements.

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