Neuropathic Ocular Pain due to Dry Eye Is Associated With Multiple Comorbid Chronic Pain Syndromes

Abstract Background/Aims The aetiology of primary chronic pain syndromes (CPS) is highly disputed. One theory suggests that pain is due to a pro-inflammatory cytokine milieu leading to nociceptive activation. We performed a systematic review and meta-analysis aiming to assess differences in cytokines levels in CPS patients versus healthy controls (HC). Methods Human studies published in English from PubMed, MEDLINE/Scopus and Cochrane databases were searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with cytokine measurements in CPS patients and HC. We excluded studies with underlying organic pathology. Quality assessment was completed using a modified version of the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. Study registered with PROSPERO (CRD42020193774). Results Initial search yielded 324 papers, 36 studies (3229 participants) eligible for systematic review and 26 studies (2048 participants) suitable for metaanalysis. There were reproducible findings supporting trends of cytokine levels comparing CPS patients with HC. Eotaxin (chemokine) however was consistently raised in CPS. Meta-analysis showed significantly increased tumour necrosis factor (TNF) (SMD=0.39, p = 0.0009, %95I=0.16-0.63, p < 0.001; I2=70%, Q2 p < 0.001), interleukin (IL)-6 (SMD=0.15, 8 (SMD=0.26, p = 0.01, 95%CI =0.05-0.47; I2=61%, Q2 p = 0.005) and IL-10 (SMD=0.61; %95 = 0.34-0.89, p < 0.001; I2 = 10%, Q2 p = 0.34) in CPS compared to HC. Conclusion We found significant differences in peripheral blood cytokine profiles of CPS patients compared to HC. However, the distinctive profile associated with CPS includes both pro-inflammatory (TNF-α, IL-6, IL-8), and anti-inflammatory cytokines (IL-10) in pooled analysis, as well as chemokine (eotaxin) signatures. Disclosure L. Furtado O'Mahony: None. A. Srivastava: None. P. Mehta: None. C. Ciurtin: None.

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Sickle cell pain: a critical reappraisal

Blood ◽

10.1182/blood-2012-04-383430 ◽

2012 ◽

Vol 120 (18) ◽

pp. 3647-3656 ◽

Cited By ~ 221

Author(s):

Samir K. Ballas ◽

Kalpna Gupta ◽

Patricia Adams-Graves

Keyword(s):

Chronic Pain ◽

Neuropathic Pain ◽

Sickle Cell ◽

Multiorgan Failure ◽

Organ Damage ◽

Acute Chest Syndrome ◽

Prodromal Phase ◽

Pain Syndromes ◽

Painful Episode ◽

Chronic Pain Syndromes

AbstractSickle cell pain includes 3 types: acute recurrent painful crises, chronic pain syndromes, and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the emergency department. It evolves through 4 phases: prodromal, initial, established, and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage, such as acute chest syndrome, multiorgan failure, and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation, and nociception. Aborting the acute painful episode at the prodromal phase could potentially prevent or minimize tissue damage. Our hypothesis is that managing these events with hydration, anti-inflammatory drugs, aggressive analgesia, and possibly vasodilators could abort the crisis and prevent or minimize further damage. Chronic pain syndromes are associated with or accompany avascular necrosis and leg ulcers. Neuropathic pain is not well studied in patients with sickle cell disease but has been modeled in the transgenic sickle mouse. Management of sickle cell pain should be based on its own pathophysiologic mechanisms rather than borrowing guidelines from other nonsickle pain syndromes.

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