HIV-associated distal neuropathic pain is associated with smaller total cerebral cortical gray matter

Abstract

Despite modern antiretroviral therapy, HIV-associated sensory neuropathy affects over 50 % of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling, and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. To better understand central nervous system contributions to HIV DNP, we performed a cross-sectional analysis of structural magnetic resonance imaging volumes in 241 HIV-infected participants from an observational multi-site cohort study at five US sites (CNS HIV Anti-Retroviral Treatment Effects Research Study, CHARTER). The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (r = -0.24; p = 0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance.

Figure 1

Multi-channel morphometry. Coronal T2 (left), T1 (middle), and segmented (right) images for anterior (top) and posterior (bottom) sections. Volumes include: ventricular (red) and subarachnoid (black) CSF, abnormal (yellow) and total (grey + yellow) white matter, cortical (blue) and subcortical (turquoise) gray matter

Figure 2

Proportion of subjects with distal neuropathic pain per quartile of adjusted log cortical volume. The line represents the fitted values (and 95% confidence intervals) from the logistic regression model. Quartile #1 represents the 53 of the 213 research subjects with the smallest log cortical volumes while quartile #4 represents the 54 subjects of the 213 research subjects with the largest log cortical volumes. The fractions (i.e. 21/53) inside each bar of the bar graph represent the proportion of the quartile of subjects with distal neuropathic pain.

Figure 3

A Partial correlation scatterplot (plot of partial residuals) shows the relationship between DNP and log-transformed cortical gray matter volume, after adjusting for all other variables in the multivariable regression model. The line represents the linear best fit for this data; correlation coefficient and p-value are described in the text.