Background & Aims

Currently, I am exploring the role of the gut-brain-spinal axis in chemotherapy-induced neuropathic rats with the intervention of fecal microbiota transplantation (FMT). My research aims to investigate the potential of FMT as a novel therapy to treat chemotherapy-induced peripheral neuropathic pain. This study used a variety of molecular biology techniques, including immunohistochemistry, western blot analysis, rtPCR, and ELISA. Focusing on this area may contribute to finding some potential therapeutic targets like-glutathione and lipid peroxidation product malonaldehyde (anti-oxidation enzymes), expression of Claudin-5 and Occludin (markers of brain-spinal integrity), and TNF-? and IL-6 (inflammatory markers). To further this goal, I plan to utilize the findings of this research to develop innovative treatments that could substantially reduce the pain and discomfort experienced by cancer patients undergoing chemotherapy.

Methods

Cisplatin-induced neuropathic pain model
Fecal microbiota transplantation as therapeutic intervention
Evan’s blue assay
Behavioral testing
2.4.1. Hargreaves Test: Thermal hyperalgesia
2.4.2 Static and dynamic mechanical allodynia test
2.4.2.1 von-Frey hair test: Static allodynia
2.4.2.2 Paint brush test: Dynamic mechanical allodynia
2.4.3 Ice-floor test: Cold hyperalgesia
2.4.4 Acetone evaporation test: Cold allodynia
2.4.5 Short nociceptive stimuli:
2.4.5.1 Pinprick test
2.8. Biochemical analysis
2.9. rt-PCR analysis
2.10. Western blotting

Results

The results could be explained by the “coasting”
property prominently exhibited by cisplatin where the toxic effect of cisplatin is known to be
persisted even after the discontinuation of the chemotherapy treatment (Authier et al., 2003) .
Thus, the maintenance of pain in cisplatin administered group could be due to prolonged
toxicity of cisplatin on the dorsal root ganglion of the sensory neurons (Borzan and Meyer,
2017). Furthermore, recent evidences have also confirmed
fecal microbiota transplantation to be an effective method to restore the healthy condition of
gut microbiota at both pre-clinical and clinical level (Cai et al., 2018; Kurokawa et al., 2018) .
In our study, we found that restoring the healthy condition of the gut microbiota by gut microbiota by fecal microbiota transplantation not only restored the blood-spinal cord integrity but also prevented
the worsening of the neuropathic pain condition.

Conclusions

From the findings of our study, we could conclude the gut microbiome to be a vital mediator
of cisplatin induced neuropathic pain. Our study revealed the fecal microbiota transplantation
to be a promising strategy which might be used as a supportive treatment alongside
chemotherapy and provides leads to the development of future strategies in the gut brain
domain that might increase the patient’s compliance with the therapy.

References

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Presenting Author

Priyanka Pandey

Poster Authors

PRIYANKA PANDEY

PhD

Department of Pharmaceutical Engineering and Technology

Lead Author

E-mail

Topics

  • Mechanisms: Biological-Systems (Physiology/Anatomy)