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Differential expression of P2X7 receptor and IL-1β in nociceptive and neuropathic pain
Benjamin Luchting1, Jens Heyn2, Tobias Woehrle1
1Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany.
Background:
Despite 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.
Methods:
P2X7R 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.
Results:
Compared 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).
Conclusions:
A 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.
Insights
Neuropathic pain (NeP) patients show increased P2X7 receptor (P2X7R) expression and IL-1β levels, unlike chronic low back pain patients. P2X7R inhibitors may treat NeP.
Area of Science:
- Immunology
- Neuroscience
- Pain Research
Background:
- Chronic pain pathogenesis and therapy are under extensive investigation.
- The ATP-gated P2X7 receptor (P2X7R) is implicated in pain models.
- The adaptive immune system's role in human chronic pain is a recent discovery.
Purpose of the Study:
- To analyze P2X7R expression on adaptive immune cells in chronic pain patients.
- To compare P2X7R expression and IL-1β serum levels in neuropathic pain (NeP) and chronic low back pain (CLBP) patients versus healthy volunteers.
- To identify patient subgroups potentially benefiting from P2X7R-modulating therapies.
Main Methods:
- Quantitative real-time PCR (qPCR) for P2X7R messenger RNA (mRNA) expression.
- Fluorescence-assisted cell sorting (FACS) for P2X7R protein expression on lymphocytes and monocytes.
- Multiplex cytokine assay for serum IL-1β levels.
Main Results:
- Significantly increased P2X7R mRNA and protein levels were observed in monocytes and lymphocytes of NeP patients compared to healthy volunteers.
- No significant changes in P2X7R expression were found in CLBP patients.
- Serum IL-1β concentrations were significantly elevated exclusively in NeP patients.
Conclusions:
- Upregulation of P2X7R and elevated IL-1β are characteristic of NeP.
- P2X7R inhibitors show potential for treating NeP.
- Clinical Trial Registration: DRKS00005954.
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