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Neuropathic Pain

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Investigation of the plasma cytokine/chemokine profile of the chronic constriction injury rat model of neuropathic pain: relevance to pharmacological reversal of allodynia. pdfDownload

1Transpharmation Ireland Ltd., Ireland, 2Transpharmation Ltd., London, United Kingdom


Neuropathic pain (NeuP) describes heterogeneous group of chronic pain disorders arising from lesion or disease of the somatosensory system.

Two anticonvulsants: gabapentin (GBP) and pregabalin (PGB) are recommended as a first line of treatment in NeuP. Unfortunately, both are associated with poor efficacy and undesirable side-effects.

Chronic constriction injury (CCI) is one of the most widely used models

Identifying a plasma biomarker to track disease progression or predict pharmacological efficacy will facilitate drug discovery in NeuP.

The aim of this study was to investigate plasma cytokine/chemokine profile in the CCI model after NeuP induction followed by GBP and PGB treatment.


The CCI model was induced in male Sprague-Dawley rats (n=16) by unilateral ligation of the sciatic nerve.

Paw withdrawal threshold (PWT; mechanical allodynia) was assessed using von-Frey hairs.

PWT was measured at:

    • baseline (BL; day 0),
    • day 20 following nerve ligation,
    • 2hr and 24hr (day 27) post-GBP (100mg/kg, p.o.)
    • 2hr and 24 hrs. (day 42/43) post-PGB (30mg/kg, p.o.).

Meso Scale Discovery (MSD) V-Plex mice Proinflammatory assay
Plasma samples from CCI rats were analysed using MSD platform:

panel v plex msd imagery


  • Reversal of increased plasma IL-5 following CCI induction was specific to GBP treatment only.
  • IL-13 a cytokine associated with suppression of NeuP, was actually increased by PGB consistent with its efficacy.
  • The plasma cytokine/chemokine profile here suggests a complex interaction between NeuP disease progression, pharmacological intervention and inflammatory signaling.
  • This study has identify potential plasma markers of NeuP progression and treatment efficacy.


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Effect of Gabapentin on paw withdrawal threshold.

ewa graphs
****p<0.0001 vs. Pre-surgery baseline (BL), $$$$p<0.0001 vs. NeuP,

Effect of Pregabalin on paw withdrawal threshold.

ewa graphs1
****p<0.0001 vs. Pre-surgery baseline (BL), $$$$p<0.0001 vs. NeuP,

Plasma: Cytokine/Chemokine expression

ewa table

ewa 2graphs

ewa2 graphs
*p<0.05, **p<0.01, ***p<0.0001 vs. BL
+p<0.05, ++p<0.01, +++p<0.0001 vs. NeuP
Values are Mean ± SEM

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