Differential expression of P2X7 receptor and IL-1β in nociceptive and neuropathic pain.

Benjamin Luchting,Shahnaz C Azad,Banafscheh Rachinger-Adam,Jens Heyn,Tobias Woehrle,Ludwig C Hinske,Simone Kreth

doi:10.1186/s12974-016-0565-z

Benjamin Luchting, Shahnaz C Azad + Show 5 more

Open Access

https://doi.org/10.1186/s12974-016-0565-z

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Abstract

BackgroundDespite substantial progress, pathogenesis and therapy of chronic pain are still the focus of many investigations. The ATP-gated P2X7 receptor (P2X7R) has previously been shown to play a central role in animal models of nociceptive inflammatory and neuropathic pain. Recently, we found that the adaptive immune system is involved in the pathophysiology of chronic nociceptive and neuropathic pain in humans. So far, data regarding P2X7R expression patterns on cells of the adaptive immune system of pain patients are scarce. We therefore analyzed the P2X7R expression on peripheral blood lymphocytes and monocytes, as well as serum levels of IL-1β in patients suffering from chronic nociceptive and neuropathic pain in comparison to healthy volunteers in order to identify individuals who might benefit from a P2X7R modulating therapy.MethodsP2X7R messenger RNA (mRNA) and protein expression were determined in patients with either chronic nociceptive low back pain (CLBP) or neuropathic pain (NeP), and in healthy volunteers by quantitative real-time PCR (qPCR) and by fluorescence-assisted cell-sorting (FACS), respectively. IL-1β serum levels were measured with a multiplex cytokine assay.ResultsCompared to healthy volunteers, P2X7R mRNA (1.6-fold, p = 0.038) and protein levels were significantly increased on monocytes (NeP: 24.6 ± 6.2, healthy volunteers: 17.0 ± 5.4; p = 0.002) and lymphocytes (NeP: 21.8 ± 6.5, healthy volunteers: 15.6 ± 5.2; p = 0.009) of patients with NeP, but not in patients with CLBP. Similarly, IL-1β serum concentrations were significantly elevated only in NeP patients (1.4-fold, p = 0.04).ConclusionsA significant upregulation of P2X7R and increased IL-1β release seems to be a particular phenomenon in patients with NeP. P2X7R inhibitors may therefore represent a potential option for the treatment of this frequently intractable type of pain.German Clinical Trial Register (DRKS): Registration Trial DRKS00005954.

Highlights

IntroductionPathogenesis and therapy of chronic pain are still the focus of many investigations
Despite substantial progress, pathogenesis and therapy of chronic pain are still the focus of many investigations
Since the adaptive immune system is critically involved in the pathophysiology of chronic pain [16], we systematically investigated the expression of P2X7 receptor (P2X7R) on lymphocytes and monocytes of patients suffering from either chronic low back pain (CLBP) or chronic neuropathic pain (NeP) in comparison to healthy volunteers

Summary

Introduction

Pathogenesis and therapy of chronic pain are still the focus of many investigations. The ATP-gated P2X7 receptor (P2X7R) has previously been shown to play a central role in animal models of nociceptive inflammatory and neuropathic pain. Data regarding P2X7R expression patterns on cells of the adaptive immune system of pain patients are scarce. Purinergic P2X receptors (P2XRs) are ATP-gated cation channels, divided into seven subtypes (P2XR1-P2XR7). They are predominantly expressed on cells of the hematopoietic lineage including macrophages, microglia, and lymphocyte subtypes [1]. The exceptional role of P2X7R in pain syndromes has been shown in various animal models of nociceptive inflammatory and neuropathic pain [2,3,4,5]. Results of experimental P2X7R inhibition in a rat model of inflammatory arthritis, induced by injection of Freund’s

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