Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell Disease: Indicators of Neuropathic Pain?

Abstract

Objectives Pain is the hallmark symptom of sickle cell disease (SCD), yet the types of pain that these patients experience, and the underlying mechanisms, have not been well characterized. The study purpose was to determine the safety and utility of a mechanical and thermal quantitative sensory testing (QST) protocol and the feasibility of utilizing neuropathic pain questionnaires among adults with SCD. Methods A convenience sample (N=25, 18 women, mean age 38.5 ± 12.5 [20–58 years]) completed self-report pain and quality-of-life tools. Subjects also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von Frey microfilaments. Results We found that the QST protocol was safe and did not stimulate a SCD pain crisis. There was evidence of central sensitization (n=15), peripheral sensitization (n=1), a mix of central and peripheral sensitization (n=8), or no sensitization (n=1). The neuropathic pain self-report tools were feasible with evidence of construct validity; 40% of the subjects reported S-LANSS scores that were indicative of neuropathic pain and had evidence of central, peripheral or mixed sensitization. Discussion The QST protocol can be safely conducted in adults with SCD and provides evidence of central or peripheral sensitization, which is consistent with a neuropathic component to SCD pain. These findings are novel, warrant a larger confirmatory study, and indicate the need for normative QST data from African American adults and older adults.

Early insights into the neurobiology of pain in sickle cell disease: A systematic review of the literature

“…[11-13] The overlapping themes of these three studies were to define a cohort of patients with SCD who experience clinical characteristics of neuropathic pain and to identify risk factors for neuropathic pain. Wilkie et al, administered the PAIN Report It to 145 adults with SCD to systematically assess sensory pain characteristics.…”

“…[12] As part of a larger study, Ezenwa et al administered two different neuropathic pain screening questionnaires [Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and Neuropathic Pain Symptom Inventory (NPSI)] to 25 adults with SCD. [13] Data revealed 40% of patients met criteria for neuropathic pain based on the S-LANSS. [13] Scoring of the NPSI does not generate a cut-point to differentiate neuropathic from non-neuropathic pain thus the proportion could not be identified, however the mean score was 27±18.6 based on a potential range of 0-100 with higher scores representing increased likelihood of neuropathic pain.…”

“…[13] Data revealed 40% of patients met criteria for neuropathic pain based on the S-LANSS. [13] Scoring of the NPSI does not generate a cut-point to differentiate neuropathic from non-neuropathic pain thus the proportion could not be identified, however the mean score was 27±18.6 based on a potential range of 0-100 with higher scores representing increased likelihood of neuropathic pain. [13] In summary, patient-reported outcome data support the existence of neuropathic pain in patients with SCD.…”

“…[13] Scoring of the NPSI does not generate a cut-point to differentiate neuropathic from non-neuropathic pain thus the proportion could not be identified, however the mean score was 27±18.6 based on a potential range of 0-100 with higher scores representing increased likelihood of neuropathic pain. [13] In summary, patient-reported outcome data support the existence of neuropathic pain in patients with SCD. Importantly, future utilization of these self-report measures could direct pain treatment clinically and allow for the selection of the correct patient pain phenotype for inclusion in neuropathic pain treatment clinical trials.…”

Mechanisms of Pain in Sickle Cell Disease

“…SCD pain can also be of neuropathic origin, which has been demonstrated in patient-reported [49,0] and QST-based studies [30]. Circulating glial ibrillary acidic protein GF"P and SP expression are signiicantly higher in subjects with SCD as compared to normal healthy subjects [ 1, 2].…”