Our group is interested in mechanisms of pathological (clinical) pain and its inhibition by opioids outside the central nervous system (CNS). This can be achieved by activation of opioid receptors on peripheral sensory neurons and immune cells within injured tissue by exogenous or endogenous opioids. The latter (endorphins, enkephalins) are produced by immune cells infiltrating inflamed tissue. Activation of such cells by stressful stimuli or releasing agents (corticotropin-releasing factor, noradrenaline, cytokines, chemokines, bacterial components) releases the opioids and ameliorates pain.
Inflammation leads to accumulation of opioid-producing immune cells as well as upregulation, enhanced axonal transport, and increased G-protein coupling of opioid receptors on peripheral sensory neurons. These mechanisms offer potential strategies for the development of new analgesic medications without CNS adverse effects (respiratory depression, sedation, nausea, vomiting) and addiction. An example is our recently developed compound, NFEPP, which inhibits pain by activation of opioid receptors exclusively in injured tissue.
We use molecular, histological, biochemical, electrophysiological, and behavioral methods combined with nanochemistry, mathematical modeling, and clinical studies in patients. We are funded by the German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), and European Union. We mentor bachelor, master, MD, and PhD students.
Opioid peptide-containing circulating leukocytes extravasate upon activation of adhesion molecules (e.g., ICAM-1; beta2 integrin). Corticotropin-releasing factor (CRF), chemokines or noradrenaline (NA, released from sympathetic neurons) can elicit opioid release by activating their respective receptors (CRF receptors, CRFR; adrenergic receptors, AR) on leukocytes. Exogenous opioids (EO) or endogenous opioid peptides (OP, green triangles) bind to opioid receptors (OR) that are synthesized in dorsal root ganglia and transported along intra axonal microtubules to peripheral (and central) terminals of sensory neurons. The subsequent inhibition of excitatory ion channels (e.g., TRPV1, Ca2+) and of substance P (sP) release results in pain inhibition.