Immunological mechanism of postherpetic neuralgia and effect of pregabalin treatment on the mechanism: a prospective single-arm observational study
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Although neuropathic pain is a severe and common pain, its pathophysiology has not been elucidated yet. Studies in recent years have focused on the immune system’s role in the pathogenesis of neuropathic pain. The aim of this study was to investigate the role of immunological mechanisms in neuropathic pain and the effect of pregabalin by measuring immunological marker levels in peripheral blood before and after pregabalin treatment in postherpetic neuralgia (PHN) patients with neuropathic pain. Methods: Forty patients diagnosed with PHN were included in the study. CD4, T follicular cells (Tfh: CD4+CXCR5+PD1+), Th17 (CD4+CCR6+ and CD4+IL17A+), regulatory T cells (Treg: CD4+ CD25+foxp3+), Th1 (CD4+ CXCR3+ and CD4+ IFN-γ+) and Th2 (CD4+ IL-4+) cell ratios were measured in peripheral blood samples before treatment and after 3 months of treatment. Results: When immunological marker and inflammation parameter levels were compared before and after treatment, the helper T cell ratio (CD3+, CD4+) was 30.28 ± 12.27% before treatment and 34.93 ± 11.70% after treatment, so there was a statistically significant increase (P = 0.028). Th17 was 4.75 ± 5.02% before treatment and 5.80 ± 3.13% after treatment, and there was a statistically significant increase (P = 0.036). Conclusions: Immunological mechanisms play an essential role in the pathogenesis of neuropathic pain, immunologically based treatment approach will be the critical point of treatment.
Abstract
Background: Although neuropathic pain is a severe and common pain, its pathophysiology has not been elucidated yet. Studies in recent years have focused on the immune system’s role in the pathogenesis of neuropathic pain. The aim of this study was to investigate the role of immunological mechanisms in neuropathic pain and the effect of pregabalin by measuring immunological marker levels in peripheral blood before and after pregabalin treatment in postherpetic neuralgia (PHN) patients with neuropathic pain. Methods: Forty patients diagnosed with PHN were included in the study. CD4, T follicular cells (Tfh: CD4+CXCR5+PD1+), Th17 (CD4+CCR6+ and CD4+IL17A+), regulatory T cells (Treg: CD4+ CD25+foxp3+), Th1 (CD4+ CXCR3+ and CD4+ IFN-γ+) and Th2 (CD4+ IL-4+) cell ratios were measured in peripheral blood samples before treatment and after 3 months of treatment. Results: When immunological marker and inflammation parameter levels were compared before and after treatment, the helper T cell ratio (CD3+, CD4+) was 30.28 ± 12.27% before treatment and 34.93 ± 11.70% after treatment, so there was a statistically significant increase (P = 0.028). Th17 was 4.75 ± 5.02% before treatment and 5.80 ± 3.13% after treatment, and there was a statistically significant increase (P = 0.036). Conclusions: Immunological mechanisms play an essential role in the pathogenesis of neuropathic pain, immunologically based treatment approach will be the critical point of treatment.
참고문헌 (42)
- Toth C, "The prevalence and impact of chronic pain with neuropathic pain symptoms in the general population", Pain Med, 10, pp.918~929 (2009)
- Tian L, "Neuroimmune crosstalk in the central nervous system and its significance for neurological diseases", J Neuroinflammation, 9, pp.155~ (2012)
- Calvo M, "The role of the immune system in the generation of neuropathic pain", Lancet Neurol, 11, pp.629~642 (2012)
- Campbell JN, "Mechanisms of neuropathic pain", Neuron, 52, pp.77~92 (2006)
- Feldman EL, "Diabetic neuropathy", Nat Rev Dis Primers, 5, pp.41~ (2019)
- Johnson RW, "Clinical practice. Postherpetic neuralgia", N Engl J Med, 371, pp.1526~1533 (2014)
- Opstelten W, "The impact of varicella zoster virus : chronic pain", J Clin Virol, 48(Suppl 1), pp.S8~S13 (2010)
- Hadley GR, "Post-herpetic neuralgia : a review", Curr Pain Headache Rep, 20, pp.17~ (2016)
- Yawn BP, "A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction", Mayo Clin Proc, 82, pp.1341~1349 (2007)
- Drolet M, "Predictors of postherpetic neuralgia among patients with herpes zoster : a prospective study", J Pain, 11, pp.1211~1221 (2010)
- Bayat A, "Anti-cytokine autoantibodies in postherpetic neuralgia", J Transl Med, 13, pp.333~ (2015)
- Luchting B, "Anti-inflammatory T-cell shift in neuropathic pain", J Neuroinflammation, 12, pp.12~ (2015)
- Kiguchi N, "Pharmacological regulation of neuropathic pain driven by inflammatory macrophages", Int J Mol Sci, 18, pp.2296~ (2017)
- Zhu SM, "Influence of systemic immune and cytokine responses during the acute phase of zoster on the development of postherpetic neuralgia", J Zhejiang Univ Sci B, 10, pp.625~630 (2009)
- Kim CF, "Interleukin-17 contributes to neuroinflammation and neuropathic pain following peripheral nerve injury in mice", J Pain, 12, pp.370~383 (2011)
- Hung AL, "Targeting cytokines for treatment of neuropathic pain", Scand J Pain, 17, pp.287~293 (2017)
- Lees JG, "Depletion of Foxp3+ regulatory T cells increases severity of mechanical allodynia and significantly alters systemic cytokine levels following peripheral nerve injury", Cytokine, 71, pp.207~214 (2015)
- Xing Q, "Role of regulatory T cells in patients with acute herpes zoster and relationship to postherpetic neuralgia", Arch Dermatol Res, 305, pp.715~722 (2013)
- Ji RR, "Pain regulation by nonneuronal cells and inflammation", Science, 354, pp.572~577 (2016)
- Ren K, "Interactions between the immune and nervous systems in pain", Nat Med, 16, pp.1267~1276 (2010)
- Davoli-Ferreira M, "Regulatory T cells counteract neuropathic pain through inhibition of the Th1 response at the site of peripheral nerve injury", Pain, 161, pp.1730~1743 (2020)
- Moalem G, "T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats", Neuroscience, 129, pp.767~777 (2004)
- Draleau K, "Phenotypic identification of spinal cord-infiltrating CD4+ T lymphocytes in a murine model of neuropathic pain", J Pain Relief, (Suppl 3), pp.003~ (2014)
- Sah DW, "Neurotrophic factors as novel therapeutics for neuropathic pain", Nat Rev Drug Discov, 2, pp.460~472 (2003)
- Kobayashi Y, "Macrophage-T cell interactions mediate neuropathic pain through the glucocorticoid-induced tumor necrosis factor ligand system", J Biol Chem, 290, pp.12603~12613 (2015)
- Kiguchi N, "Peripheral interleukin-4 ameliorates inflammatory macrophage-dependent neuropathic pain", Pain, 156, pp.684~693 (2015)
- Hao S, "HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain", Mol Pain, 2, pp.6~ (2006)
- Sorge RE, "Different immune cells mediate mechanical pain hypersensitivity in male and female mice", Nat Neurosci, 18, pp.1081~1083 (2015)
- Austin PJ, "Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis", Pain, 153, pp.1916~1931 (2012)
- Langley RG, "Secukinumab in plaque psoriasis--results of two phase 3 trials", N Engl J Med, 371, pp.326~338 (2014)
- Attal N, "EFNS guidelines on the pharmacological treatment of neuropathic pain : 2010 revision", Eur J Neurol, 17, pp.1113~e88 (2010)
- Tesfaye S, "Diabetic neuropathies : update on definitions, diagnostic criteria, estimation of severity, and treatments", Diabetes Care, 33, pp.2285~2293 (2010)
- Kanazi G, "Treatment of postherpetic neuralgia—an update", J Peripher Nerv Syst, 5, pp.250~ (2000)
- Güleç H, "Combination treatment of post-herpetic neuralgia", J Contemp Med, 4(2 EK), pp.100~137 (2014)
- Higa K, "T-lymphocyte subsets in otherwise healthy patients with herpes zoster and relationships to the duration of acute herpetic pain", Pain, 51, pp.111~118 (1992)
- Asanuma H, "Frequencies of memory T cells specific for varicella-zoster virus, herpes simplex virus, and cytomegalovirus by intracellular detection of cytokine expression", J Infect Dis, 181, pp.859~866 (2000)
- Austin PJ, "The neuro-immune balance in neuropathic pain : involvement of inflammatory immune cells, immune-like glial cells and cytokines", J Neuroimmunol, 229, pp.26~50 (2010)
- Kohm AP, "Cutting Edge : anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells", J Immunol, 176, pp.3301~3305 (2006)
- Suntharalingam G, "Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412", N Engl J Med, 355, pp.1018~1028 (2006)
- Abdel-Moneim A, "The potential pathogenic role of IL-17", Th17 cells in both type 1 and type 2 diabetes mellitus, 2018, pp.101, 287~292
- Noma N, "Interleukin-17 levels in rat models of nerve damage and neuropathic pain", Neurosci Lett, 493, pp.86~91 (2011)
- Kleinschnitz C, "T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression", Exp Neurol, 200, pp.480~485 (2006)
