Interventions to prevent and reverse chronic spinal sensitization in rat models of non-specific low back pain.

• Applicants: Professor Dr. Siegfried Mense; Professor Dr. Rolf-Detlef Treede
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Cognitive, Systems and Behavioural Neurobiology
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 317559845

The studies are designed to test the hypothesis that sensitization of dorsal horn neurons with input from low back muscles and thoracolumbar fascia is a key factor for the development of non-specific chronic low back pain and depends on two main mechanisms: 1. Increased afferent input from peripheral nociceptors. Often, the nociceptive input occurs unnoticed by the patient, but it may cause a latent sensitization of spinal dorsal horn neurons. 2. Dysfunction of the descending pain-modulating systems. In this mechanism, stress plays an important role. The hypothesis will be tested in three animal models of low back pain: namely 1. inflammation of the multifidus muscle or thoracolumbar fascia, 2. non-inflammatory nociceptive input elicited by repeated injections of nerve growth factor (NGF), and 3. stress due to immobilization. The methods include electrophysiological in vivo recordings from dorsal horn neurons combined with behavioral experiments. This combination is important, because preliminary data show that central sensitization can occur without any behavioral changes. Further; by chronic intrathecal drug administration the relevance of spinal signaling pathways between glial cells and neurons in the latent sensitization will be tested. The aims of the study are: 1. To find out to what extent spinal signaling pathways between neurons, microglia and astrocytes, are involved in the sensitization of lumbar dorsal horn neurons in our 3 models of LBP (series 1 and 2). In connection with this aim, we hope to gain new insights into the substances that are involved in the latent sensitization of the neurons. 2. To see if and how blocking the descending pain-modulating systems or the sympathetic system influence the nociceptive and stress-induced spinal sensitization. 3. To see if there are inflammation-induced changes (e.g. branching patterns, number of varicosities) in peripheral nociceptive and sympathetic nerve endings in the thoracolumbar fascia. In the experiments connected to aims 1 and 2, treatments will be tested that have the potential to prevent, attenuate or reverse the chronic sensitization. The final aim is to generate data on the mechanisms underlying non-specific low back pain that cannot be obtained in patients, and to find out if parallels between the 3 low back pain models and different groups of low back pain patients (e.g. lesion-induced, stress-induced) exist.

• DFG Programme: Research Grants