Mitochondrial reactivity following acute exposure to experimental pain testing in people with HIV and chronic pain.

Background: Physical stressors can cause a physiological response that can contribute to an increase in mitochondrial dysfunction and Mitochondrial DNA damage (mtDNA damage). People living with HIV (PWH) are more likely to suffer from chronic pain and may be more susceptible to mitochondrial dysfunction following exposure to a stressor. We used Quantitative Sensory Testing (QST) as an acute painful stressor in order to investigate whether PWH with/without chronic pain show differential mitochondrial physiological responses. Methods: The current study included PWH with (n = 26), and without (n = 29), chronic pain. Participants completed a single session that lasted approximately 180 min, including QST. Blood was taken prior to and following the QST battery for assays measuring mtDNA damage, mtDNA copy number, and mtDNA damage-associated molecular pattern (DAMP) levels (i.e., ND1 and ND6). Results: We examined differences between those with and without pain on various indicators of mitochondrial reactivity following exposure to QST. However, only ND6 and mtDNA damage were shown to be statistically significant between pain groups. Conclusion: PWH with chronic pain showed greater mitochondrial reactivity to laboratory stressors. Consequently, PWH and chronic pain may be more susceptible to conditions in which mitochondrial damage/dysfunction play a central role, such as cognitive decline.

Enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.

Chronic pain in persons living with HIV (PLWH) may be related to alterations in endogenous pain modulatory processes (e.g., high facilitation and low inhibition of nociception) that promote exaggerated pain responses, known as hyperalgesia, and central nervous system (CNS) sensitization. This observational study examined differences in endogenous pain modulatory processes between 59 PLWH with chronic pain, 51 PLWH without chronic pain, and 50 controls without HIV or chronic pain. Quantitative sensory testing for temporal summation (TS) of mechanical and heat pain as well as conditioned pain modulation (CPM) were used to assess endogenous pain facilitatory and inhibitory processes, respectively. Associations among TS, CPM, and self-reported clinical pain severity were also examined in PLWH with chronic pain. Findings demonstrated significantly greater TS of mechanical and heat pain for PLWH with chronic pain compared to PLWH without chronic pain and controls. CPM effects were present in controls, but not in either PLWH with or without chronic pain. Among PLWH with chronic pain, greater TS of mechanical pain was significantly associated with greater average clinical pain severity. Results of this study suggest that enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.

Intersectional health-related stigma in persons living with HIV and chronic pain: implications for depressive symptoms.

"Intersectional health-related stigma" (IHRS) refers to stigma that arises at the convergence of multiple health conditions. People living with HIV (PLWH) and chronic pain have two highly stigmatized health conditions, and thus may be at especially high risk for internalizing these stigmas and consequently experiencing depression. This study examined the intersectionality of internalized HIV and chronic pain stigma in relation to depressive symptoms in a sample of PLWH and chronic pain. Sixty participants were recruited from an HIV clinic in the Southeastern United States. Chronic pain was defined as pain that has been present for at least three consecutive months, and that has been an ongoing problem for at least half the days in the past six months. All participants completed the HIV Stigma Mechanisms Scale, Internalized Stigma in Chronic Pain Scale, the Short-Form Brief Pain Inventory, and the Center for Epidemiological Studies - Depression Scale. Clinical data was collected from medical records. An intersectional HIV and chronic pain composite variable was created and participants were categorized as either high (28%), moderate (32%), or low (40%). Results revealed that intersectional HIV and chronic pain stigma was significantly associated with severity of depressive symptoms (p = .023). Pairwise contrasts revealed that participants with high (p = .009) and moderate (p = .033) intersectional stigma reported significantly greater mean depressive symptom severity than those with low intersectional stigma. Participants who reported the highest levels of internalized HIV and chronic pain stigma also reported the greatest severity of depressive symptoms. This suggests that the experience of both HIV and chronic pain stigma (i.e., IHRS) among PLWH and chronic pain may synergistically perpetuate negative mood in a more profound manner than experiencing either one stigma alone.

Detectable Viral Load May Be Associated with Increased Pain Sensitivity in Persons Living with HIV: Preliminary Findings.

OBJECTIVE: Animal models have previously shown that HIV is associated with hyperalgesia, or heightened sensitivity to painful stimuli. Efforts to determine whether this finding translates to humans are presently lacking. Among persons living with HIV (PLWH), those with detectable viral loads may be at greatest risk for heightened pain sensitivity. It was hypothesized that PLWH with detectable viral loads would be more sensitive to painful stimuli compared with PLWH without detectable viral loads and healthy controls without HIV. DESIGN: A total of 47 PLWH and 50 community-dwelling, healthy adults without HIV (controls) were recruited. Participants completed a quantitative sensory testing protocol to assess threshold, tolerance, and temporal summation in response to painful mechanical and heat stimuli. Most recent viral load was collected from medical records, and viral load was considered detectable if the count was greater than 50 copies/mL of blood. Of the 47 PLWH, 11 (23.4%) had detectable viral loads, the median viral load count was 10,200 copies/mL. RESULTS: PLWH with detectable viral loads demonstrated significantly lower pain thresholds for mechanical stimuli (F2,89 = 3.15, P = 0.049), significantly lower heat pain tolerances (F2,89 = 3.38, P = 0.039), and significantly greater temporal summation of heat pain at 48 °C (F2,89 = 10.66, P < 0.001) and 50 °C (F2,89 = 3.82, P = 0.026), compared with PLWH without detectable viral loads and healthy controls. CONCLUSIONS: These preliminary results tentatively suggest that the detectable presence of the virus may sensitize PLWH to painful mechanical and heat stimuli.

Sex and Gender are Not the Same: Why Identity Is Important for People Living with HIV and Chronic Pain.

BACKGROUND: Sex differences in pain sensitivity have been well documented, such that women often report greater sensitivity than men. However, clinical reports highlighting sex differences often equate gender and sex. This is a particularly critical oversight for those whose gender identity is different than their genetic sex. METHODS: This preliminary study sets to analyze differences in pain responses between cisgender and transgender individuals living with HIV and chronic pain. A total of 51 African-American participants (24 cisgender men, 20 cisgender women, 7 transgender women) with similar socioeconomic status were recruited. Genetic sex, gender identity, depression and anxiety, pain severity, pain interference and pain-related stigma were recorded. Participants also completed a quantitative sensory testing battery to assess pain in response to noxious heat and mechanical stimuli. RESULTS: Transgender women and cisgender women demonstrated a greater magnitude of temporal summation for heat pain stimuli or mechanical stimuli compared to cisgender men. Specifically, transgender women reported greater mechanical summation than either cisgender women or cisgender men. Transgender women and cisgender women similarly reported greater chronic pain severity compared to cisgender men. CONCLUSION: These data support the notion that gender identity may play a more significant role in pain sensation than genetic sex. These results further maintain that not only gender identity and genetic sex are distinct variables but that treatment should be based on identity as opposed to genetic sex.

Pain-Specific Resilience in People Living With HIV and Chronic Pain: Beneficial Associations With Coping Strategies and Catastrophizing.

OBJECTIVE: Chronic pain is increasingly recognized as a common and disabling problem for people living with HIV (PLWH). In a recent systematic review of psychosocial factors associated with chronic pain in PLWH, it was reported that very few studies to date have examined protective psychological factors that might help mitigate chronic pain for PLWH. The current study examined pain-specific resilience in relation to clinical and experimental pain, as well as pain coping in PLWH and chronic pain. Pain-specific resilience specifically refers to the ability to maintain relatively stable, healthy levels of psychological and physical functioning in the face of ongoing and persistent pain. METHODS: A total of 85 PLWH (mean CD4 = 643; 13% detectable viral load ≥200; 99% on antiretroviral therapy) who met criteria for chronic pain (>3 consecutive month's duration) were enrolled. Medical records were reviewed to confirm clinical data. All participants provided sociodemographic information prior to completing the following validated measures: Pain Resilience Scale (PRS), Coping Strategies Questionnaire-Revised (CSQ-R), Center for Epidemiologic Studies - Depression Scale (CES-D), and the Brief Pain Inventory - Short Form (BPI-SF). They then completed a quantitative sensory testing battery designed to assess tolerance for painful heat and cold stimuli. RESULTS: In adjusted multiple regression models controlling for covariates, greater pain-specific resilience was significantly associated with less pain interference (p = 0.022) on the BPI-SF, less pain catastrophizing (p = 0.002), greater use of distraction (p = 0.027) and coping self-statements (p = 0.039) on the CSQ-R, as well as significantly greater heat pain tolerance (p = 0.009). Finally, results of a parallel multiple mediation model demonstrated that the effect of pain-specific resilience on heat pain tolerance was indirectly transmitted through less pain catastrophizing (95% confidence interval:0.0042 to 0.0354), but not use of distraction (95% confidence interval: -0.0140 to 0.0137) or coping self-statements (95% confidence interval: -0.0075 to 0.0255). CONCLUSION: The findings suggest that pain-specific resilience may promote adaptation and positive coping in PLWH and chronic pain.

Social support buffers the negative influence of perceived injustice on pain interference in people living with HIV and chronic pain.

INTRODUCTION: A growing literature attests to the overwhelming prevalence of disabling chronic pain among people living with HIV (PLWH), yet very little is known about psychosocial contributors to poor chronic pain outcomes in this population. Pain-related perception of injustice may promote pain interference by hindering engagement in daily activities among individuals with chronic pain. Social support has been shown to buffer the negative impact of harmful beliefs on well-being and facilitate adjustment to chronic pain. OBJECTIVE: This cross-sectional study tested the buffering hypothesis of social support to determine whether increasing levels of social support mitigate the negative influence of perceived injustice on pain interference. METHODS: A total of 60 PLWH with chronic pain completed measures of perceived injustice, social support, pain severity, and interference, as well as depressive symptoms. RESULTS: In a regression-based model adjusted for age, sex, depressive symptoms, and pain severity, results indicated that social support significantly moderated (ie, buffered) the association between perceived injustice and pain interference (P = 0.028). Specifically, it was found that perceived injustice was significantly associated with greater pain interference among PLWH with low levels of social support (P = 0.047), but not those with intermediate (P = 0.422) or high levels of social support (P = 0.381). CONCLUSION: Pain-related injustice perception reflects harmful beliefs regarding severity of loss consequent to chronic pain development, a sense of unfairness, and irreparability of loss. Access to a social support network may provide an adaptive means of mitigating the negative effects of perceived injustice.