Despite antiretroviral therapy, HIV-associated distal neuropathic pain (DNP) remains one of the most prevalent, disabling and treatment-resistant complications of HIV disease, affecting approximately 20% of patients. Distal sensory neuropathy (DSP) is defined clinically by the presence of abnormal signs on clinical examination. Only a subset of HIV+ individuals with evidence of distal sensory nerve injury by clinical examination experiences DNP. This suggests that some other influence, such as alterations in the CNS processing of afferent sensory information, may modify the phenotypic expression of DSP. We hypothesized that brain pain processing regions would show smaller regional volumes in HIV patients with DNP compared to HIV patients without DNP. To investigate this hypothesis, we performed a cross-sectional analysis of structural magnetic resonance images in 236 HIV-infected participants (66 with DNP and 170 without DNP) from an observational multi-site cohort study at five US sites (CNS HIV Antiretroviral Treatment Effects Research Study, CHARTER). Using standardized ratings and semi-structured interviews, study clinicians classified DNP (burning, aching, or shooting) into five categories of severity: none, slight (occasional, fleeting), mild (frequent), moderate (frequent, disabling), and severe (constant, daily, disabling). The association between DNP and regional cortical volumes was investigated using permutation-based multivariable regression controlling for demographic and clinical factors (age, site, ethnicity, gender, skull volume, drug abuse, and neurocognitive impairment). For these 236 subjects, 101 showed no signs of peripheral neuropathy (9 of these subjects reported DNP), 68 showed 1 sign of neuropathy (20 of these reported DNP), and 67 reported 2 or more signs of neuropathy (37 of these reported DNP). We found that HIV-associated DNP is significantly correlated with smaller regional brain volumes in the left ventral posterior cingulate cortex (p=.035; MNI coordinates x=-6, y=-52, z=20). These results are consistent with previous chronic pain structural brain imaging research.
© 2013 Published by Elsevier Inc.