Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients

Koch, A.; Zacharowski, KD; Boehm, Olaf; Stevens, Markus F.; Lipfert, P.; Giesen, H-J. von; Wolf, Achim; Freynhagen, Rainer

doi:10.1007/s00011-007-6088-4

Cited by 175 publications

(137 citation statements)

References 43 publications

(57 reference statements)

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“…In recent clinical studies, elevated levels of proinflammatory cytokines (IFN-c, IL-1b, IL-2, IL-6 and TNF-a) correlated with elevated pain scores in various types of neurological and rheumatologic disorders [11][12][13][14][15][16][17][18][19][20]. In addition, we found that intervertebral TNF-a levels correlate with preoperative pain in LDH patients [21].…”

Section: Discussionmentioning

confidence: 51%

“…For instance, studies of complex regional pain syndrome, painful neuropathies and intervertebral disc degeneration indicate that a local elevation of proinflammatory cytokines is directly related to the amount of pain [11,13,22]. Yet studies in patients with neuropathic, nociceptive and mixed types of chronic pain show that elevated peripheral markers related to pain sensation [12,14,15,19]. We are equally in the dark regarding the temporal resolution of neuroinflammatory markers during the transition from an initial precipitating event to chronic pain.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous in vitro and animal models of pain have demonstrated the contribution of proinflammatory cytokines to peripheral and central nociception [5][6][7][8][9][10]. Also in human, local and systemically expressed proinflammatory cytokines have been implicated as mediators of pain [11][12][13]. Among these, TNF-a, IL-1b and IL-6 are particularly interesting because of their hyperalgesic effects after nerve damage.…”

Section: Introductionmentioning

confidence: 99%

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Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain

et al. 2012

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Purpose Previous experimental models have shown that proinflammatory cytokines modulate peripheral and central nociception. However, the direct correlation between inflammation and pain in patients remains unclear. Our aim is to correlate the levels of inflammation in the spine with pre-and postoperative pain scores after discectomy. Methods Paravertebral muscle, annulus fibrosus (AF) and nucleus pulposus (NP) biopsies were intraoperatively collected from ten lumbar disc hernia (LDH) patients suffering from chronic sciatic pain and, as painless controls, five scoliosis patients. IL-1b and IL-6 expressions in these biopsies were assessed by qPCR and western blot. The amount of pain, indicated on a 0-10 point visual analogue scale (VAS), was assessed 1 day before surgery and 6 weeks and 1 year after surgery. For analysis purposes, LDH patients were grouped into painful (VAS C 3.5) and non-painful (VAS \ 3.5). LDH painful patient group showed a onefold increased mRNA expression of IL-1b in the NP, and IL-6 in the AF and NP (p \ 0.05 vs. controls).Results By western blot analysis, both cytokines were clearly visible in all LDH biopsies, but not in controls. However, cytokine expression of the painful patient group did not differ from those of the non-painful patient group. In addition, there was no correlation between VAS scores and either marker. Conclusions These findings support the idea that LDH is accompanied by a local inflammatory process. Yet, the lack of correlation between IL-1b or IL-6 expression and the severity pain suggests that these cytokines may not play a leading role in maintaining a pain generating network.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain

et al. 2012

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“…Macrophages increase the levels of multiple inflammatory mediators, especially IL-6 and IL-8, nitric oxide, TNF-a, and IL-1b [36]. The levels of these cytokines have correlated with pain intensity in patients, and persistent activation of sensory fibers upregulates nitric oxide synthase, thereby increasing the level of nitric oxide, suggesting a possible positive feedback loop of pain generation [39].…”

Section: If the Disc Is Aneural And Avascular Why Does It Cause So Mmentioning

confidence: 99%

Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

Kadow

Sowa

et al. 2015

Clinical Orthopaedics &Amp; Related Research

212

194

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Background Intervertebral disc degeneration is a common condition with few inexpensive and effective modes of treatment, but current investigations seek to clarify the underlying process and offer new treatment options. It will be important for physicians to understand the molecular basis for the pathology and how it translates to developing clinical treatments for disc degeneration. In this review, we sought to summarize for clinicians what is known about the molecular processes that causes disc degeneration.

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“…Recent studies have linked inflammatory molecules to pain pathophysiology [10][11][12][13][14][15]. These studies, however, did not focus on the identification of a surrogate Research Article Luchting, Hinske, Rachinger-Adam, Celi, Kreth & Azad marker for pain intensity.…”

mentioning

confidence: 99%

Soluble Intercellular Adhesion Molecule-1: A Potential Biomarker for Pain Intensity in Chronic Pain Patients

et al. 2017

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Aim: Pain therapy is strongly guided by patients' self-reporting. However, when self-reporting is not an option, pain assessment becomes a challenge and may lead to undertreatment of painful conditions. Pain is a complex and multifactorial phenomenon. Recent work has connected pain pathophysiology also with the inflammatory system. We therefore hypothesized that pain intensity could be predicted by cytokine-levels. Patients & methods: In this observational, single-center study, we investigated 30 serum cytokines to predict pain intensity in a screening/follow-up set of 95 chronic pain patients and controls. We then prospectively validated soluble intercellular adhesion molecule-1 (sICAM-1)'s discriminatory capability (n = 21). Results & conclusion: sICAM-1 was significantly associated with patient-reported pain intensity and yielded differential serum levels in patients of varying degrees of pain intensity. Changes in pain ratings over time correlated with changes in sICAM-1 levels. Our findings suggest the possibility of a clinical use of sICAM-1 as a potential biomarker for pain intensity.

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Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients

Abstract: Pro-inflammatory cytokines (IL-1beta, IL-2, IL-6, IFN-gamma, TNF-alpha) in the plasma correlate with increasing pain intensity. Chronic pain patients show a significant increase in plasma levels of NO in comparison to healthy controls.

Cited by 175 publications

References 43 publications

Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain

Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain

Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

Soluble Intercellular Adhesion Molecule-1: A Potential Biomarker for Pain Intensity in Chronic Pain Patients

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