Brain Responses to Noxious Stimuli in Patients With Chronic Pain

Abstract

IMPORTANCE Functional neuroimaging is a valuable tool for understanding how patients with chronic pain respond to painful stimuli. However, past studies have reported heterogenous results, highlighting opportunities for a quantitative meta-analysis to integrate existing data and delineate consistent associations across studies. OBJECTIVETo identify differential brain responses to noxious stimuli in patients with chronic pain using functional magnetic resonance imaging (fMRI) while adhering to current best practices for neuroimaging meta-analyses.

Dysregulated anterior insula reactivity as robust functional biomarker for chronic pain—Meta‐analytic evidence from neuroimaging studies

“…The present study employed two different CBMA approaches (GingerALE and ABC) to determine whether chronic pain disorders are characterized by neurofunctional dysregulations during experimental pain induction. In contrast to two recent neuroimaging meta‐analyses, which, surprisingly, did not reveal convergent functional alterations in chronic pain disorders (Tanasescu et al, 2016; A. Xu et al, 2021), the present study shows robust evidence for altered neurofunctional processing in the left anterior insular cortex of chronic pain patients during experimental pain induction. Notably, functional abnormalities in the left anterior insula cortex were robustly confirmed on Dataset #1 with both ALE and ABC approaches, although with subtle differences, and on Dataset #2 with ABC.…”

“…Early neuroimaging meta‐analyses performed on chronic pain suffered from a bias toward false‐positive results since they employed previous ALE versions (Eickhoff et al, 2017). However, two robust recent meta‐analyses conducted with LocaleALE (Tanasescu et al, 2016) and with the GingerALE updated version (A. Xu et al, 2021) did not determine robust neurofunctional differences between chronic pain patients and control individuals during experimental pain induction. The null findings in the previous studies (Tanasescu et al, 2016; A. Xu et al, 2021) might be explained by study selection criteria.…”

“…Early investigations mainly employed the Activation Likelihood Estimation (ALE) algorithm (Eickhoff et al, 2009; Turkeltaub, Eden, Jones, & Zeffiro, 2002), however until 2016 (GingerALE version 2.3.5), this algorithm suffered from drawbacks in the code (Eickhoff, Laird, Fox, Lancaster, & Fox, 2017) that, plausibly, invalidated several of these findings. Two more recent neuroimaging meta‐analyses re‐examined functional alterations in chronic pain patients during experimental pain processing utilizing either the updated version of the GingerALE algorithm (A. Xu et al, 2021) or a different algorithm (LocalALE; Tanasescu, Cottam, Condon, Tench, & Auer, 2016). However, both meta‐analyses did not identify convergent neurofunctional alterations in chronic pain patients.…”

“…On this background, we performed a meta‐analysis on fMRI studies to determine convergent neurofunctional alterations in chronic pain conditions during acute pain processing. Considering that the negative findings in previous meta‐analyses on chronic pain (Tanasescu et al, 2016; A. Xu et al, 2021) might be related to the high degree of heterogeneity of the selected studies, we adopted very stringent selection criteria to circumscribe this problem. First, in line with the recent meta‐analysis from Xu et al (A. Xu et al, 2021), we selected only studies directly comparing chronic pain patients and healthy participants.…”

“…Considering that the negative findings in previous meta‐analyses on chronic pain (Tanasescu et al, 2016; A. Xu et al, 2021) might be related to the high degree of heterogeneity of the selected studies, we adopted very stringent selection criteria to circumscribe this problem. First, in line with the recent meta‐analysis from Xu et al (A. Xu et al, 2021), we selected only studies directly comparing chronic pain patients and healthy participants. This allowed us to avoid considerable heterogeneity introduced by different experimental settings, such as it occurs employing studies conducted separately in either pain patients or in healthy controls.…”