Background & Aims
Background:
Chemotherapy-induced peripheral neuropathy (CIPN), particularly due to paclitaxel, remains a chronic, debilitating, and dose-limiting adverse effect. Neuro-immune activation and oxidative stress have been implicated in the pathogenesis of paclitaxel-induced peripheral neuropathy. Benfotiamine, a lipid soluble thiamine analogue, has increased bioavailability over thiamine and has shown anti-inflammatory, antinociceptive, and neuroprotective effects experimentally. However, there is no evidence for effects of benfotiamine in paclitaxel-induced peripheral neuropathy.
Aim:
To investigate the effect of benfotiamine in paclitaxel-induced peripheral neuropathy and to elucidate mechanisms involved in alleviating pain hypersensitivity.
Methods
CIPN was induced by intraperitoneal injections of paclitaxel (2 mg/kg) for four alternate days. Thermal hyperalgesia and mechanical allodynia were assessed and pro-inflammatory cytokine, TNF-?, level was estimated in DRG and spinal cord. The extent of oxido-nitrosative stress was assessed by estimating TBARS and nitrite levels, and SOD activity.
Results
Administration of paclitaxel evoked pain hypersensitivity characterized by marked thermal hyperalgesia and mechanical allodynia and that parallel to increase in the markers of neuro-immune activation and oxidative stress. Benfotiamine (100 and 300 mg/kg, po) administration for 2 weeks started 14 days after paclitaxel injection significantly alleviated pain hypersensitivity observed as reversal of established thermal hyperalgesia and mechanical allodynia on days 21 and 28. These observed antihyperalgesic and antiallodynic effects of benfotiamine on paclitaxel-induced neuropathic pain are accompanied by marked reduction of TNF-?, in both DRG and spinal cord as well as markers of oxido-nitrosative stress in spinal cord.
Conclusions
These findings provide an evidence for antinociceptive potential of benfotiamine partly by inhibiting neuro-immune activation and in part by reducing oxido-nitrosative stress in paclitaxel-induced neuropathy and represent a novel therapeutic approach for alleviation of CINP clinically.
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Presenting Author
Satyanarayana Padi
Poster Authors
Satyanarayana Padi
PhD
Care College of Pharmacy
Lead Author
Haritha Pasupulati
MPharm
Bharat School of Pharmacy, Hyderabad, TS; Sri Padmavati Mahila Visva Vidyalayam, Tirupati, AP
Lead Author
Sujatha Dodoala
PhD
IPT, Sri Padmavati Mahila Visva Vidyalayam (Women’s University), Tirupati, Andhra Pradesh, India
Lead Author
Prasad Koganti
PhD
IPT, Sri Padmavati Mahila Visva Vidyalayam (Women’s University), Tirupati, Andhra Pradesh, India
Lead Author
Topics
- Models: Chronic Pain - Neuropathic