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Neuropathic Pain

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Investigation of the temporal plasma cytokine/chemokine profile of the monosodium iodoacetate rat model of osteoarthritis: relevance to pharmacological reversal of hyperalgesia pdfView

J. A. PRENDERVILLE1, E. SOKOLOWSKA1, M. BIANCHI1, A.L. THOMAS2, C. MONTAGUT-BORDAS3, A.S. FISHER2, N. UPTON2, A.H. DICKENSON3
1Transpharmation Ireland Ltd., Dublin, Ireland, 2Transpharmation Ltd., London, United Kingdom, 3University College London, London, United Kingdom

Introduction

  • Osteoarthritis (OA) is estimated to affect 10-15% of individuals over the age of 60 (World Health Organisation, 2013)

  • OA affects load bearing joints and often leads to pain and disability

  • Identifying biomarkers associated with efficacy of pharmacological interventions will facilitate drug discovery in OA

Aims:

  1. Investigate the pharmacological efficacy of gold standard analgesic drugs in the monosodium-iodoacetate (MIA) rat model of OA

  2. Examine the temporal plasma cytokine/chemokine profile in the MIA model of OA

Methods

The OA model was induced in 3 cohorts of male Sprague-Dawley rats (n=105) by intra-articular injection (knee joint) of the glycolysis inhibitor MIA (80mg/ml; 0.025ml/rat)

Weight-bearing was measured using an incapacitance meter at baseline and hyperalgesia induced by MIA was measured

Cohort 1:
- Days 3-7 (early phase): Daily administration of vehicle, celecoxib (50mg/kg, PO) or pregabalin (30mg/kg)

Cohort 2:
- Days 24-28 (late phase): Daily administration of vehicle, celecoxib (50mg/kg, PO) or pregabalin (30mg/kg, PO)

Cohort 3:
- Days 0, 4, 7, 14: Blood sampling and plasma isolation

Plasma cytokines/chemokines were analysed using an MSD multiplexed assay

pro inf panel jack v plex msd diagram jack

Conclusions

  • Hyperalgesia was reversed by the non-steroidal anti-inflammatory drug (NSAID) celecoxib during the early inflammatory phase of the model
  • Pregabalin reversed hyperalgesia during the late neuropathic phase
  • The inflammatory mediator KC/GRO is acutely increased in plasma after OA induction
  • The pro-inflammatory cytokine TNFa was decreased in plasma from day 3 after MIA administration
  • The anti-inflammatory cytokines IL-4 and IL-10 are increased in plasma after the inflammatory phase of the model
  • These data suggest plasma inflammatory markers may indicated OA disease progression and could be used to inform treatment strategy

Contact

www www.transpharmation.co.uk
at This email address is being protected from spambots. You need JavaScript enabled to view it.
twitter @JackPrendervill / @TranspharmLtd

Results

Early phase (days 3-7) : Effects of celecoxib and pregabalin on hyperalgesia

jack graphical

Late phase (days 24-28) : Effects of celecoxib and pregabalin on hyperalgesia

jack graphical1

*P<0.05, ***P<0.001, Values are mean ± SEM, Repeated measures ANOVA


Plasma: Cytokine/Chemokine expression

table jack

jack graphical2 jack graphical3
jack graphical4 jack graphical5

*P<0.05, **P<0.01, ***P<0.001
+P<0.05, ++P<0.01
#P<0.05, ##P<0.01
Values are mean ± SEM, Repeated measures ANOVA

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