Increasing age is associated with elevated circulating interleukin-6 and enhanced temporal summation of mechanical pain in people living with HIV and chronic pain

Abstract

Introduction: In the current antiretroviral treatment era, people living with HIV (PLWH) can achieve a near-normal life expectancy. However, as PLWH grow older, they are increasingly prone to developing chronic health conditions including pain. One possible explanation for increased pain in older populations with HIV is that aging is associated with inflammation and altered pain modulatory processes (ie, increased facilitation and decreased inhibition). Objectives: Our study aimed to examine how age affects endogenous pain modulatory processes in PLWH with chronic pain and to examine how age affects serum inflammatory cytokines. Methods: A total of 80 PLWH (median CD4+ = 646; 24% detectable viral load >50; 99% on antiretroviral therapy) with chronic pain provided demographic information (age, sex, and race) and completed standardized questionnaires to assess mood and clinical pain severity. Blood assays were completed to determine circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-α, as well as CD4+ and HIV viral load. Temporal summation of mechanical pain and conditioned pain modulation assessed pain facilitation and inhibition, respectively. Results: Mean age was 48.9 (8.2) years; range: 26 to 67, with 45% >50 years. In adjusted multiple regression models, increasing age was associated with elevated levels of circulating IL-6 (P < 0.01), but not tumor necrosis factor-α. Increasing age was also associated with enhanced temporal summation of mechanical pain (P < 0.01), but not conditioned pain modulation. Greater circulating levels of IL-6 were correlated with enhanced temporal summation of mechanical pain (r = 0.304, P < 0.01), but the association was no longer significant after adjustment for covariates. Conclusion: Findings suggest that high levels of some circulating proinflammatory cytokines as well as enhanced pain facilitatory processes together may contribute to the chronic pain experienced by older adults with HIV.

People living with HIV and the emerging field of chronic pain—what is known about epidemiology, etiology, and management

“…Some findings suggest that peripheral neurons experience inflammation indirectly through HIV-infected monocyte-macrophage lineage cells that excrete inflammatory cytokines [24,[49][50][51]. Inflammation persists in many, even with viral load suppression [52,53]. This is a picture seen in other chronic pain illnesses such as fibromyalgia.…”

“…Some are specific to HIV, such as avascular necrosis and osteoporosis with subsequent fracture [57], while others are less specific to HIV such as lumbosacral pain [13] and fibromyalgia [55]. In cohorts of patients with multi-site and non-neuropathic pain, elevated inflammatory cytokines were associated with increasing age and with worsening measures of chronic pain [52,53]. Multi-site pain is associated with long duration of exposure to HIV, immuno-suppression, and exposure to many different ART [58].…”