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. 2018 May 10;67(2):259-269.
doi: 10.1538/expanim.17-0090. Epub 2018 Jan 12.

The effect of thiamine and its metabolites on peripheral neuropathic pain induced by cisplatin in rats

Didem Onk  1 , Renad Mammadov  2 , Bahadir Suleyman  2 , Ferda Keskin Cimen  3 , Murat Cankaya  4 , Vahdet Gul  5 , Durdu Altuner  2 , Onur Senol  6 , Yucel Kadioglu  6 , Ismail Malkoc  7 , Halis Suleyman  2
Affiliations

The effect of thiamine and its metabolites on peripheral neuropathic pain induced by cisplatin in rats

Didem Onk et al. Exp Anim. .

Abstract

Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study aimed to investigate the effects of thiamine and TPP on cisplatin-induced peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2 mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8 days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter. IL-1β, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were determined in blood samples. Histopathological examinations were performed on removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups were calculated to be 21.3% and 82.9%, respectively. Increased production of IL-1β and MDA by cisplatin was inhibited by TPP, while it was not inhibited by thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group. Histopathological and biochemical investigations demonstrated that hyperalgesia and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels. These results indicate that cisplatin inhibits the formation of TPP from thiamine, leading to severe PNP. This finding suggests that TPP may be more beneficial than thiamine for the treatment of cisplatin-induced PNP.

Keywords: cisplatin; pain; peripheral neuropathy; rat; thiamine..

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Figures

Fig. 1.
Fig. 1.
Serum levels of MDA (A) and tGSH levels (B) in the rat groups (n=6, for each group). *P<0.0001 compared with the HG group. **P<0.0001, compared with the CIS group.
Fig. 2.
Fig. 2.
Serum IL-1β levels in the rat groups (n=6, for each group). *P<0.0001, compared with the HG group. **P<0.0001, compared with the CIS group.
Fig. 3.
Fig. 3.
Serum thiamine (A) and TPP (B) levels in the rat groups (n=6, for each group). *P<0.0001, compared with the HG group. **P<0.0001, compared with the CIS group.
Fig. 4.
Fig. 4.
Normal structures of the sciatic nerve, epineurium (line arrow), vessels (circle arrow), adipose tissue (smooth arrow), perineurium (square arrow), and nerve fascicles (bilateral arrow) in the HG (A) and epineurium (arrow), blood vessels in the epineurium (star) and nerve fascicles (arrow) TM (B) and TPP (C) rat groups (n=6, for each group) (scale bar=100 µm).
Fig. 5.
Fig. 5.
A: Vascular congestion in the epineurium layer of the sciatic nerve tissue in the CIS rat group. B: Destruction and edema in the nerve fascicles of the CIS rat group. C: Fascicular destruction determined by S-100 staining of the sciatic nerve in the CIS rat group. D: Fascicular destruction determined by trichrome staining of the sciatic nerve in the CIS rat group.
Fig. 6.
Fig. 6.
Fascicular destruction (round arrow), edema (line arrow), and vascular congestion (smooth arrow) structure in the CTM rat group (n=6, for each group).
Fig. 7.
Fig. 7.
Edema (straight arrow) in sciatic nerve tissue of the CTPP rat group (n=6, for each group).
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