Background & Aims
Chemotherapy-induced neuropathic pain (CINP) is a distressing complication frequently associated with the use of paclitaxel, a common chemotherapeutic agent. Current therapeutics for CINP exhibit limited efficacy and pose challenges due to potential central side effects, including sedation, respiratory depression, cognitive impairment, and addiction. In response to these clinical limitations, this study investigates the therapeutic potential of Dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripherally acting mu-opioid receptor agonist, in a rat model of CINP.
Methods
The primary objective of this study is to assess the analgesic properties of DALDA and elucidate the underlying mechanisms governing its therapeutic activity. A rat model of CINP is employed to evaluate the effects of DALDA treatment on paclitaxel-induced evoked and spontaneous ongoing pain. Molecular analyses are conducted to examine the expression of key pain-related markers, including TRP channels, NR2B, voltage-gated sodium channels (VGSCs), and neuroinflammatory markers in both the dorsal root ganglion (DRG) and the spinal cord (L4-L5 region) of rats.
Results
Our findings reveal that DALDA treatment significantly ameliorates paclitaxel-induced pain in rats without inducing drug addiction or central side effects. Molecular analyses demonstrate that paclitaxel administration increases the expression of TRP channels, NR2B, VGSCs, and neuroinflammatory markers in the DRG and spinal cord. However, DALDA treatment effectively downregulates ion channels (TRPs, VGSCs) and NR2B, concurrently inhibiting microglial activation. This results in the suppression of oxido-nitrosative stress and the neuroinflammatory cascade.
Conclusions
The study suggests that peripheral mu-opioid receptors, targeted by DALDA, present a promising avenue for the treatment of CINP. By alleviating pain without inducing central side effects, DALDA offers a potential solution to the challenges associated with current therapeutics. This research opens new possibilities for enhanced pain relief strategies in patients undergoing chemotherapy, emphasizing the importance of targeting peripheral mu-opioid receptors in managing CINP.
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Presenting Author
Vinod Tiwari
Poster Authors
Vinod Tiwari and PhD
PhD
Indian Institute of Technology (BHU)
Lead Author
Anagha Gadepalli
Indian Institute of Technology (BHU), Varanasi
Lead Author
Obulapathi Ummadisetty
M. Pharm
IIT (BHU)
Lead Author
Akhilesh .
Indian Institute of Technology BHU, Varanasi India
Lead Author
Deepak Chouhan
Indian Institute of Technology (B.H.U)
Lead Author
Krushna Eknath Yadav
M.Pharm
IIT (BHU)
Lead Author
Topics
- Specific Pain Conditions/Pain in Specific Populations: Cancer Pain & Palliative Care