Pressure Pain Threshold and Pain Diary Data in Patients with Sickle Cell Disease
Authors: Meiler Steffen E. , Wells Leigh G , Bowman Latanya , Bora Pritam , Xu Hongyan , Fillingim Roger B , Clair Betsy , Sayer Gloria , Kutlar Abdullah 
Published: October 2019

Abstract
Abstract 1007
Pain is a common and serious complication of sickle cell disease (SCD), which is frequently disabling and difficult to treat. Acute painful crises account for the vast majority of healthcare encounters (> 90% of hospitalizations), and many patients with SCD suffer from chronic pain. Despite several well designed clinical studies, which have brought to light the high incidence and severity of pain in this patient population, sickle cell pain remains an understudied, undermanaged, and poorly understood condition. Previous work has largely relied on self-reporting instruments, such as carefully designed pain diaries to study the epidemiology of pain in this patient cohort. In contrast, very little is known about the usefulness of methods that measure pain in response to a standardized stimulus and the correlation of experimentally induced pain to more traditional instruments such as pain diaries and opioid use. In this study we explored the use of pressure algometry to measure pain thresholds in adult patients with SCD.
Our study enrolled 167 adult patients with SCD [163 SS, 1 SD Los Angeles, 3 Sβ0-thal; 108 on Hydroxyurea (HU), 59 off HU; 83 females and 84 males; mean age 31 years (range 16–61)] and forty racially matched controls (23 females and 17 males; mean age 35 years (range 17–61). The pain threshold, defined as the lowest pressure at which pain is induced, was measured by pressure algometry in three anatomic muscle groups (masseter, trapezius, and ulnar). Four measurements were obtained at each site and averaged for analysis. 118 patients were tested with a manual algometer (Wagner FDIX™, Wagner Instruments, Greenwich, CT) and 49 patients with a computerized model (Algomed, Medoc Ltd., Israel). The data sets for the two algometer groups were highly correlated for each anatomic site and were therefore combined for the final analysis (Pearson's correlation coefficients: masseter readings, r=0.78, p=2.73E-09; trapezius readings, r=0.85, p=4.28E-12; ulnar readings, r=0.68, p=3.26E-06). In addition, self-reported pain and distress were monitored prospectively for six months using a validated pain diary (ordinal scales of 0–9, respectively; J Natl Med Assoc. 2005 February; 97(2): 183–193). Opioid use, expressed as morphine equivalents, and the frequency of vaso-occlusive events are being recorded prospectively for twelve months. Algometer readings were compared using a linear model with age and gender as covariates. Data are reported as mean ± SEM. A p-value of < 0.05 is significant.
Adult patients with SCD experienced pain at significantly lower pressures at all anatomic sites tested compared to racially matched controls. Pain threshold measurements in the ulnar muscle group achieved the best discrimination between sickle cell and control subjects. (Patients vs. controls (KPa): Masseter: 150± 4.35 vs. 193± 13.24, p= 1.99E–05; trapezius: 265±10.23 vs. 383± 37.99, p= 2.78E–05; ulnar: 371±10.26 vs. 518±34.59, p= 6.28E–09). Ulnar algometer readings also correlated with self-reported pain scores (r=-0.226, p=0.0097). There was no correlation between pain threshold measurements and self-reported distress or the use of hydroxyurea.
Quantitative sensory testing revealed that adult patients with SCD are hyperalgesic in response to a standardized pressure stimulus. Of the three anatomic sites tested, ulnar pain threshold readings produced the strongest separation between sickle cell and control subjects and correlated with self-reported pain. Quantitative sensory testing may provide a useful research and clinical tool to study the biological mechanisms of pain in SCD and the therapeutic efficacy of psychosocial and pharmacological interventions.

Disclosures:
Fillingim: Algynomics: Consultancy, Shareholder Other.