Provoked cytokine response is not associated with distress or induced secondary hyperalgesia in people with suppressed HIV.

Journal: medRxiv : the preprint server for health sciences

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Affiliated Institutions:  African Pain Research Initiative, Department of Anaesthesia and Perioperative Medicine, Neuroscience Institute, University of Cape Town, Cape Town, South Africa. National Heart and Lung Institute, Imperial College London, London, UK. School of Biomedicine, University of Adelaide, South Australia, Australia. Division of Allergy and Clinical Immunology, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Rondebosch, South Africa. Chronic Pain and Fatigue Research Center, Department of Anesthesiology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA. Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Boston, Massachusetts, USA. HIV Mental Health Research Unit, Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Abstract summary 

Psychological distress predicts the onset and worsening of persistent pain, but the mechanisms that underpin this influence are poorly understood. Pro-inflammatory signalling is a plausible mechanistic link, given its known connections to distress, pain, and neural upregulation. Sustained distress may prime the inflammatory system to respond more strongly to a phasic noxious challenge, supporting neuroimmune upregulation of central nociceptive signalling and persistent pain. This cross-sectional study tested the hypotheses that endotoxin-provoked expression of typically pro-inflammatory cytokines (IL1β, IL6) is a partial mediator between distress and persistent pain, and that it is associated with the secondary hyperalgesia response to an experimental noxious challenge, in people with suppressed HIV. Study participants were 99 adults (mean (range) age: 43(28-64y/o; 72 females) with either no pain (n=54) or persistent pain (n=45), mostly of black South African ethnicity, low socio-economic status, and with high social support. The results replicated previous reports that distress is associated with persistent pain status and pain severity, and also showed an association between distress and the anatomical extent of pain. However, distress was not associated with provoked cytokine expression, nor was provoked cytokine expression associated with secondary hyperalgesia. The conflict between our findings and the evidence on which our hypotheses were based could reflect masking of an effect by differentially trained immune systems or a more complex relationship arising from diverse psychoneuroimmunological interactions in this sample. Our sample's combination of HIV status, African genetic ancestry, financial impoverishment, and rich social interconnectedness is poorly represented in current research and represents an opportunity to deepen insight into psychoneuroimmunological interactions related to distress and persistent pain.

Authors & Co-authors:  Madden Victoria J VJ Mqadi Luyanduthando L Arendse Gwen G Bedwell Gillian J GJ Msolo Ncumisa N Lesosky Maia M Hutchinson Mark R MR Peter Jonathan G JG Schrepf Andrew A Parker Romy R Edwards Robert R RR Joska John A JA

Study Outcome 

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Citations :  Albrecht D, Kim M, Torrado-Carvajal A, Akeju O, Edwards R, Wasan A, Zhang Y, Bergan C, Protsenko E, Hooker J, Napadow V, Loggia M. Glial activation in chronic back pain: replication of the original observation and association with negative affect. The Journal of Pain 2018;19(3):S2.
Authors :  12
Identifiers
Doi : 2025.01.21.25320673
SSN : 
Study Population
Male,Female
Mesh Terms
Other Terms
HIV;cytokines;hyperalgesia;hypersensitivity;inflammation;neuroimmunomodulation;pain;psychological distress;secondary hyperalgesia
Study Design
Cross Sectional Study
Study Approach
Country of Study
South Africa
Publication Country
United States