Exploration of cerebral connectivity in central disinhibition via thermal grill illusion and functional imaging.

• Applicant: Privatdozentin Dr. Julia Forstenpointner
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2020 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437219459

Descending modulation of pain is considered to be altered (diminished) in chronic pain. The knowledge of structures and mechanisms involved in the modulation of endogenous pain dynamics is constrained. Therefore, central activation mechanisms involved in central disinhibition pain processing should be explored via functional MRI by evaluating structures such as the periaqueductal gray. The underlying pathophysiological mechanisms of central disinhibition involve a dysfunctional A-delta fiber inhibition of peripheral C-fiber input as well as an impaired integration of thermal sensations in the lateral and medial thalamic region. Alternatively, a spinal convergence of cold and warm afferents into the nociceptive system via wide dynamic range (WDR) neurons was postulated. However, these brain measures of disinhibition may be different within healthy subjects as well as compared to patients. In fact, previous studies point to an alteration of structures related to an endogenous pain modulation in fibromyalgia patients, by exploring these structures this study might add to a better understanding of pain generation and chronification in fibromyalgia pathogeneses.In order to carry out the experiments, central disinhibition effect should be induced by a 3D-printer custom build thermal grill illusion device (50x50x30mm, polypropylene) in 40 healthy volunteers and 20 patients with fibromyalgia. The thermal grill illusion induces a burning pain sensation due to an alternating arrangement of non-noxious heat (40°C) and cool (20°C) bars. Additionally, descending pain modulation capacity will be evaluated via offset-analgesia. The aims are: (1) To determine differences of cerebral connectivity with age 20-30yrs [n=20] and 50-60yrs [n=20]; (2) To determine sex differences of cerebral connectivity in men [n=20] and women [n=20] and (3) To determine differences of cerebral connectivity in healthy controls vs. patients (fibromyalgia). The understanding of endogenous pharmacological mechanisms such as epinephrine reuptake inhibition, presumably one key mechanism in descending pain inhibition as well as pharmacological target of substances such as duloxetine, tramadol or tapentadol is a prerequisite for an adequate mechanism based therapy. Therefore, the identification of key structures and mechanisms, linking central disinhibition to endogenous pain inhibition may contribute substantially to the understanding and management of neuropathic pain states.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor David Borsook, Ph.D.