title: Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.
abstract: Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Harvard Medical School, Departments of Anesthesiology, Perioperative, Pain Medicine, and Psychiatry, Brigham and Women's Hospital, Pain Management Center, Chestnut Hill, MA, USA Department of Acute and Chronic Care, Johns Hopkins University School of Nursing, Baltimore, MD, USA.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Campbell
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Carroll
authors.forename: Kasey
authors.initials: K
authors.lastname: Kiley
authors.forename: Dingfen
authors.initials: D
authors.lastname: Han
authors.forename: Carlton
authors.initials: C
authors.lastname: Haywood
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanzkron
authors.forename: Lauren
authors.initials: L
authors.lastname: Swedberg
authors.forename: Robert R
authors.initials: RR
authors.lastname: Edwards
authors.forename: Gayle G
authors.initials: GG
authors.lastname: Page
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Haythornthwaite
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D055815:Young Adult
chemical_list: D016207:Cytokines