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TLR 2 and 4 responsiveness from isolated peripheral blood mononuclear cells from rats and humans as potential chronic pain biomarkers.

Authors: Kwok, YH  Tuke, J  Nicotra, LL  Grace, PM  Rolan, PE  Hutchinson, MR 
Citation: Kwok YH, etal., PLoS One. 2013 Oct 30;8(10):e77799. doi: 10.1371/journal.pone.0077799. eCollection 2013.
Pubmed: (View Article at PubMed) PMID:24204973
DOI: Full-text: DOI:10.1371/journal.pone.0077799

BACKGROUND: Chronic pain patients have increased peripheral blood mononuclear cell Interkeukin-1beta production following TLR2 and TLR4 simulation. Here we have used a human-to-rat and rat-to-human approach to further investigate whether peripheral blood immune responses to TLR agonists might be suitable for development as possible systems biomarkers of chronic pain in humans. METHODS AND RESULTS: Study 1: using a graded model of chronic constriction injury in rats, behavioral allodynia was assessed followed by in vitro quantification of TLR2 and TLR4 agonist-induced stimulation of IL-1beta release by PBMCs and spinal cord tissues (n = 42; 6 rats per group). Statistical models were subsequently developed using the IL-1beta responses, which distinguished the pain/no pain states and predicted the degree of allodynia. Study 2: the rat-derived statistical models were tested to assess their predictive utility in determining the pain status of a published human cohort that consists of a heterogeneous clinical pain population (n = 19) and a pain-free population (n = 11). The predictive ability of one of the rat models was able to distinguish pain patients from controls with a ROC AUC of 0.94. The rat model was used to predict the presence of pain in a new chronic pain cohort and was able to accurately predict the presence of pain in 28 out of the 34 chronic pain participants. CONCLUSIONS: These clinical findings confirm our previous discoveries of the involvement of the peripheral immune system in chronic pain. Given that these findings are reflected in the prospective graded rat data, it suggests that the TLR response from peripheral blood and spinal cord were related to pain and these clinical findings do indeed act as system biomarkers for the chronic pain state. Hence, they provide additional impetus to the neuroimmune interaction to be a drug target for chronic pain.


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RGD Object Information
RGD ID: 8553185
Created: 2014-05-07
Species: All species
Last Modified: 2014-05-07
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.