Mitochondrial DNA Copy Number and Damage in People with HIV and Chronic Pain

Abstract

Mitochondrial DNA (mtDNA) is integral to mitochondrial function and cellular energy production. Lack of protective histones and limited repair capacity make mtDNA fragile and susceptible to injury. HIV infection and antiretroviral therapy is associated with mitochondrial depletion and damage, likely due to oxidative stress. Mitochondrial damage has been implicated in widespread musculoskeletal pain among people with Fibromyalgia. Whether mtDNA depletion and damage is associated with chronic pain in people with HIV has not yet been addressed. Participants included 24 PWH and chronic pain and 22 PWH without chronic pain, who were recruited from an HIV Clinic at a major medical campus. Participants completed quantitative sensory testing (QST) that included thermal and mechanical noxious stimuli. Blood was drawn before and after QST. Assays of mtDNA copy number and damage were completed to examine whether differences could be detected, 1) following completion of QST (i.e., across the 2 time points), and/or 2) between the groups (i.e., PWH and chronic pain versus PWH without chronic pain). Repeated measures analysis demonstrated that mtDNA copy number significantly decreased following completion of QST for both PWH with and without chronic pain (p\u202f=\u202f.027). There was a significant interaction between mtDNA damage and chronic pain status (p=.006). Specifically, PWH and chronic pain demonstrated greater mtDNA damage following QST in comparison to PWH without chronic pain. This study provides novel evidence suggesting that mitochondrial depletion and damage may be associated with chronic pain in PWH. Further research is needed to confirm whether mitochondrial damage is causally implicated in the development of chronic pain and fatigue that frequently accompanies HIV. Oxidative stress-related to HIV infection and ART warrants further investigation as a potential physiological pathway linking mitochondrial function and chronic pain in PWH. UAB Center for AIDS Research (P30AI027767), NHLBI (R01HL147603).