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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

1Transpharmation Ireland Ltd., Dublin, Ireland, 2Transpharmation Ltd., London, United Kingdom, 3University College London, London, United Kingdom


  • 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


  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


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


  • 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


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twitter @JackPrendervill / @TranspharmLtd


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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