Altered cytokine levels in the blood and cerebrospinal fluid of chronic pain patients

Bačkonja, Miroslav; Coe, Christopher L.; Müller, Daniel; Schell, Kathleen

doi:10.1016/j.jneuroim.2008.01.005

Cited by 126 publications

(101 citation statements)

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“…Supporting the anti-nociceptive and anti-inflammatory properties of IL-10, the administration of exogenous IL-10: 1) decreases TNF␣ induced hyperalgesia and 2) produces prolonged reversal of neuropathic pain when administered in the intrathecal space (Milligan et al, 2006a;Milligan et al, 2006b;Wagner et al, 1998). Clinical research has documented further that there are significantly lower levels of IL-10 in the CSF of patients with chronic pain as compared to age-matched healthy controls (Backonja et al, 2008). It was only in the CC group that there was an inverse correlation between the CSF IL-10 concentrations and spontaneously reported pain intensity and discomfort (Table 3).…”

Section: Discussionmentioning

confidence: 98%

“…Elevated CSF pro-inflammatory cytokine levels indicative of excessive neuroinflammation are thought to be associated with chronic pain states, and have been reported in patients with chronic nociceptive (Lundborg et al, 2010;Backonja et al, 2008;Bjurstrom et al, 2016) as well as neuropathic pain (Kotani et al, 2004). Besides signs of neuroinflammation as reflected by CSF cytokine indices, brain positron emission tomography (PET) scans of patients with chronic back pain show microglial cell specific activation (greater than healthy controls) in: 1) medial thalamic, 2) post central gyrus, and 3) paracentral lobule, suggesting that chronic pain mediated neuroinflammation and central sensitization likely co-occur in both the brain and spinal cord (Loggia et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

Lerman

Davis

Bertram

et al. 2016

Psychoneuroendocrinology

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a b s t r a c tObjective: Although posttraumatic stress disorder (PTSD) and chronic pain frequently occur in tandem, the pathophysiological mechanisms mediating this comorbidity are poorly understood. Because excessive inflammation occurs in both conditions, we examined the cerebrospinal fluid (CSF) concentrations of inflammatory response mediators interleukin 1-beta (IL-1␤), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF␣) and interleukin 10 (IL-10) after prolonged suprathreshold pain stimulus in 21 male combat veterans; 10 with PTSD and 11 combat controls (CC). Methods: After completing baseline quantitative sensory testing (QST) and psychological profiling, all patients received an injection of capsaicin into the quadriceps muscle. Spontaneously reported pain was measured for 30 min after the capsaicin injection. The evoked pain measure of temporal summation was tested between 70 and 110 min post capsaicin injection. Inflammatory (IL-1␤, IL-6, IL-8 TNF␣) and antiinflammatory (IL-10) CSF cytokines were measured before (baseline) and after capsaicin injection over a time frame of 110 min. Results: Following intramuscular capsaicin injection, pro-inflammatory cytokines [TNF␣, IL-6, IL-8] significantly increased (percent rise from baseline) in both groups, whereas IL-1␤ significantly increased in the PTSD group only. The anti-inflammatory cytokine IL-10 showed an immediate (within 10 min) increase in the CC group; however, the IL-10 increase in the PTSD group was delayed and not consistently elevated until 70 min post injection. Conclusion: These findings show significant central nervous system (CNS) differences in the inflammatory response to a deep pain stimulus in combat veterans with and without PTSD. They support the concept that abnormally elevated neuroinflammatory response to pain stimuli may be one CNS mechanism accounting for the high co-occurrence of PTSD and pain.Published by Elsevier Ltd.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

Lerman

Davis

Bertram

et al. 2016

Psychoneuroendocrinology

Self Cite

View full text Add to dashboard Cite

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“…In regards to neuropathic pain, human studies investigating cytokine profiles in the cerebrospinal fluid (CSF) have indicated that it may be the balance between proinflammatory and anti-inflammatory cytokine profiles here that is important. Backonja et al (2008) found that CSF soluble tumor necrosis factor receptor and IL-1b were positively correlated with pain intensity in patients with distal painful nondiabetic polyneuropathy or post-traumatic neuralgia, whereas IL-10 was inversely correlated with pain severity. Other studies have reported the severity of neuropathic pain in patients with noninflammatory polyneuropathy and complex regional pain syndrome to be positively correlated with serum and CSF concentrations of proinflammatory cytokines (Alexander et al, 2005;Ludwig et al, 2008).…”

Section: Brain Inflammation Is Associated With Pain and Depressionmentioning

confidence: 92%

Neuroinflammation and Comorbidity of Pain and Depression

et al. 2013

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“…[14][15][16][17] The cytokines that could present abnormal levels in blood and cerebrospinal fluid include interleukin-8 (IL-8), interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and soluble TNF receptor (sTNF-R). 18 One challenge in interpreting the cytokine levels reported in many papers has been the limited information on healthy norms and reference values. 19,20 …”

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confidence: 99%

Serum cytokine levels in patients with chronic low back pain due to herniated disc: analytical cross-sectional study

et al. 2010

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CONTEXT AND OBJECTIVE: The role of immune response and proinflammatory cytokines in the pathogenesis of chronic pain has been of growing interest. In order to evaluate whether there is any association between disc herniation and elevated cytokine levels, we measured cytokine levels in patients with chronic low back pain and in healthy subjects. DESIGN AND SETTING:Analytical cross-sectional study at the Pain Clinic of Universidade Federal da Bahia (UFBA). METHODS:Cytokine levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique on 23 patients with low back pain (G1) and on 10 healthy subjects (G2). RESULTS:The levels of tumor necrosis factor-alpha [TNF-alpha] (G1 = 5.6 ± 2.3 pg/ml; G2 = 1.6 ± 0.5 pg/ml; P = 0.01) and interleukin-6[IL-6] (G1 = 4.1 ± 3.0 pg/ml; G2 = 0.9 ± 0.4 pg/ml; P = 0.01) were higher in G1. There were no statistically significant differences in relation to interleukin-1 [IL-1] (G1 = 0.5 ± 0.3 pg/ml; G2 = 0.5 ± 0.1 pg/ml; P = 1) or soluble tumor necrosis factor receptor [sTNF-R] (G1 = 572 pg/ml ± 36; G2 = 581 ± 50 pg/ml; P = 0.87). CONCLUSION:The patients with chronic low back pain due to disc herniation presented higher levels of TNF-alpha and IL-6, but not of IL-1 or sTNF-R. RESUMO CONTEXTO E OBJETIVO:A função da resposta imunológica e das citocinas pró-inflamatórias na patogênese da dor crônica tem tido interesse crescente. Para avaliar se há correlação entre hérnia de disco e aumento de citocinas, foi medida a concentração de citocinas em pacientes com lombalgia crônica e em indivíduos sadios. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado na Clínica de Dor da Universidade Federal da Bahia (UFBA).MÉTODO: As concentrações de citocinas foram medidas pela técnica de ELISA (enzyme linked immunosorbent assay) em 23 pacientes com lombalgia (G1) e 10 sadios (G2). RESULTADOS:As concentrações de fator-alfa de necrose tumoral [TNF-alpha] (G1 = 5.6 ± 2.3 pg/ml; G2 = 1.6 ± 0.5 pg/ml; P = 0,01) e interleucina-6 [IL-6] (G1 = 4.1 ± 3.0 pg/ml; G2 = 0.9 ± 0.4 pg/ml; P = 0,01) foram maiores no G1. Não houve diferença estatisticamente significante para interleucina-1 [IL-1] (G1 = 0.5 ± 0.3 pg/ml; G2 = 0.5 ± 0.1 pg/ml; P = 1) e receptor solúvel do factor de necrose tumoral [sTNF-R] (G1 = 572 pg/ml ± 36; G2 = 581 ± 50 pg/ml; P = 0,87).CONCLUSÃO: Os pacientes com lombalgia crônica por hérnia de disco apresentam concentrações maiores de TNF-alpha e IL-6, mas não de IL-1 ou sTNF-R.

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Altered cytokine levels in the blood and cerebrospinal fluid of chronic pain patients

Cited by 126 publications

References 52 publications

Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

Neuroinflammation and Comorbidity of Pain and Depression

Serum cytokine levels in patients with chronic low back pain due to herniated disc: analytical cross-sectional study

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