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Fig. 2 | Arthritis Research & Therapy

Fig. 2

From: Fatigue in chronic inflammation - a link to pain pathways

Fig. 2

Mechanisms of interaction between peripheral inflammation, the nervous system and the hypothalamic-pituitary-adrenal (HPA) axis involved in the fatigue process. In the HPA axis, the hypothalamus contains neurons that synthesize corticotropin-releasing hormone (CRH), which regulates adrenocorticotropic hormone (ACTH) by the pituitary gland. ACTH stimulates the synthesis of glucocorticoids such as cortisol by the adrenal cortex and catecholamines by the adrenal medulla of the adrenal gland. Cortisol could have a negative feedback mechanism on the brain. Glucocorticoids inhibit many functions of leukocytes and the production of pro-inflammatory cytokines (interleukin (IL)-6 and IL-1) by immune cells. ACTH and CRH have pro-inflammatory properties and IL-1, IL-6 and tumor necrosis factor (TNF)-α activate the HPA axis. The peripheral nervous system can affect inflammation: the sympathetic neurons of the autonomic nervous system (ANS) secrete pro- and anti-inflammatory neuropeptides. These pro-inflammatory cytokines could enter central nervous system (CNS) areas by the permeable blood–brain barrier or facilitate the release of second messengers to induce cytokine activity in the brain. With excess inflammation, the activity of some CNS neurotransmitters could be altered

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