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bioRxiv · 10.1101/2022.04.26.489572

Inflammation as a Silent Partner in Opioid Addiction: A Regulatory Logic Model

Toole, J. T.·Morris, M. C.·Lyman, C. A.·Spink, G.·Broderick, G.
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Abstract

The brain and body consist of complex networks of interconnected feedback and feed forward loops. Because these networks are capable of supporting multiple homeostatic states, a stressor or combination of stressors may cause the network to become "stuck" in a persistent maladaptive state, for example, chronic pain and the potentiation of opioid dependency. The current research uses automated text mining of over 14,000 publications to assemble a regulatory circuit consisting of 44 immune and neurotransmission mediators linked by 188 documented regulatory interactions. Decisional logic parameters dictating the regulatory dynamics available to each network model were estimated such that predicted behavior would adhere to observed pathologies. Analysis of this psycho-neuroimmune network confirmed that a broad family of behavioral kinetics may be equally capable of supporting dynamically stable conditions of chronic pain, persistent depression and addiction behaviors. Despite differences in the predicted course of onset, these models typically point to characteristic patterns of increased inflammatory activity in the brain for each of these pathologies, specifically increased expression of the protein complex NF-kB and inflammatory signaling proteins IL1-B, IL6, and TNF. Potential treatments targeting both addiction and chronic pain may therefore benefit from the use of anti-inflammatory drugs as pharmacological potentiators of current behavioral interventions. Clinical RelevanceThis work establishes a methodology for understanding both illness-specific and shared mechanisms underlying addiction, chronic pain, and depression, and the corresponding expression profiles of psychoneuroimmune markers that might facilitate screening and treatment design.

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Toole, J. T., Morris, M. C., Lyman, C. A., Spink, G., Broderick, G.. 2022-04-27. Inflammation as a Silent Partner in Opioid Addiction: A Regulatory Logic Model. https://doi.org/10.1101/2022.04.26.489572

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