HIV Distal Neuropathic Pain Is Associated with Smaller Ventral Posterior Cingulate Cortex

Abstract

Objective. Despite modern antiretroviral therapy, HIV-associated neuropathy is one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of distal neuropathic pain is not fully explained by the degree of peripheral nerve damage. A better understanding of brain structure in HIV distal neuropathic pain may help explain why some patients with HIV neuropathy report pain while the majority does not. Previously, we reported that more intense distal neuropathic pain was associated with smaller total cerebral cortical gray matter volumes. The objective of this study was to determine which parts of the cortex are smaller.Methods. HIV positive individuals with and without distal neuropathic pain enrolled in the multisite (N 5 233) CNS HIV Antiretroviral Treatment Effects (CHARTER) study underwent structural brain magnetic resonance imaging. Voxel-based morphometry was used to investigate regional brain volumes in these structural brain images.Results. Left ventral posterior cingulate cortex was smaller for HIV positive individuals with versus without distal neuropathic pain (peak P 5 0.017; peak t 5 5.15; MNI coordinates x 5 26, y 5 254, z 5 20). Regional brain volumes within cortical gray matter structures typically associated with pain processing were also smaller for HIV positive individuals having higher intensity ratings of distal neuropathic pain.Conclusions. The posterior cingulate is thought to be involved in inhibiting the perception of painful stimuli. Mechanistically a smaller posterior cingulate cortex structure may be related to reduced anti-nociception contributing to increased distal neuropathic pain.

Migraine improvement correlates with posterior cingulate cortical thickness reduction

“…Bilateral reduction in regional cerebral blood flow has been documented in the cingulofrontal transitional cortex and posterior cingulate cortex during noxious stimulation of the left hand 35 . Similar to our results, in patients with HIV-associated distal neuropathic pain, changes (increase) were restricted to the left posterior cingulate cortex 36 . A negative correlation between pain thresholds and cortical thickness was also reported on the left 22 .…”

Central Nervous System Correlates of “Objective” Neuropathy in Alcohol Use Disorder

“…Brain regions that correlated with perception of vibration included frontal precentral, frontal medial, and temporal superior cortices; the cingulate mid-posterior cortex, implicated in pain perception, and previously reported as relevant to both diabetic and HIV-related neuropathies (Sugimine et al, 2016, Hsieh et al, 2015, Keltner et al, 2017); the thalamus, relevant to perception of pain (Geha and Apkarian, 2005, Peyron et al, 2000), and sometimes directly implicated in neuropathy (Selvarajah et al, 2011); and the pons, which has been reported in case studies of rare neuropathies (cf., Weinmann, 1967, Rossi et al., 1986). Consistent with posterior cingulate involvement, our recent study in HIV found relations between subjective symptoms of neuropathy and smaller parietal precuneus volume (Zahr et al, 2019); both regions support introspection and self-awareness (Kjaer et al, 2002, Jacob and Kostev, 2016).…”

“…Recent evidence supports Central Nervous System (CNS) involvement in peripheral neuropathy (e.g., Tesfaye et al, 2016, Zahr et al, 2019, Keltner et al, 2017, Pfefferbaum et al, 2009). Diabetes with neuropathy relative to diabetes without neuropathy is associated with compromise in volume of cingulate cortex (Boland et al, 2014), implicated in the affective processing of pain (Coppieters et al, 2017, Buckalew et al., 2008, Absinta et al, 2012).…”

“…Diabetes with neuropathy relative to diabetes without neuropathy is associated with compromise in volume of cingulate cortex (Boland et al, 2014), implicated in the affective processing of pain (Coppieters et al, 2017, Buckalew et al., 2008, Absinta et al, 2012). Similarly, distal neuropathic pain symptoms in HIV are associated with deficits in posterior cingulate volume (Keltner et al, 2017).…”

A critical evaluation of validity and utility of translational imaging in pain and analgesia: Utilizing functional imaging to enhance the process

“…Similar to CIPN, HIV patients often present with neuropathy and neuropathic pain (Ellis et al, 2010; Wiebe et al, 2011), but here, nerve injury can be due to the infection itself or result from treatment-induced toxicity (Kranick and Nath, 2012). In HIV, changes in CNS structure (Chiang et al, 2007; Jahanshad et al, 2012; Keltner et al, 2014; Thompson et al, 2005; Thompson and Jahanshad, 2015), for instance, those occurring in posterior cingulate cortex, may contribute to the spectrum of symptoms reported by HIV patients and also objectively distinguish painful vs. painless HIV neuropathy (Keltner et al, 2016).…”