Protective role of natural killer cells in neuropathic pain conditions

ABSTRACT: During the past few years, the research of chronic neuropathic pain has focused on neuroinflammation within the central nervous system and its impact on pain chronicity. As part of the ERA-Net NEURON consortium, we aimed to identify immune cell patterns in the cerebrospinal fluid (CSF) of patients with herpes zoster neuralgia and patients with polyneuropathy (PNP), which may contribute to pain chronicity in these neuropathic pain conditions. Cerebrospinal fluid of 41 patients (10 herpes zoster and 31 PNP) was analyzed by flow cytometry identifying lymphocyte subsets: CD4+ (T-helper cells), CD8+ (cytotoxic T cells), CD19+ (B cells), and CD56+ (natural killer [NK]) cells. At baseline and at follow-up, the somatosensory phenotype was assessed with quantitative sensory testing. In addition, the patients answered epidemiological questionnaires and the PainDETECT questionnaire. Immune cell profiles and somatosensory profiles, as well as painDETECT questionnaire scores, were analyzed and correlated to determine specific immune cell patterns, which contribute to chronic pain. We found a negative correlation (P = 0.004, r = -0.596) between the frequency of NK cells and mechanical pain sensitivity (MPS), one of the most relevant quantitative sensory testing markers for central sensitization; a high frequency of NK cells correlated with low MPS. The analysis of the individual follow-up showed a worsening of the pain condition if NK-cell frequency was low. Low NK-cell frequency is associated with signs of central sensitization (MPS), whereas high NK-cell frequency might prevent central sensitization. Therefore, NK cells seem to play a protective role within the neuroinflammatory cascade and may be used as a marker for pain chronicity.