Prof. Dr. Norbert Weidner
Spinal Cord Injury Centre, Medical Faculty Heidelberg, Heidelberg University
Dr. Radhika Puttagunta
Spinal Cord Injury Centre, Medical Faculty Heidelberg, Heidelberg University
Prof. Dr. Frank Bradke
German Centre for Neurodegenerative Diseases (DZNE), University of Bonn

Functional and structural plasticity following spinal cord injury: contributions to chronic central neuropathic pain


The debilitating secondary consequences of neuropathic pain after spinal cord injury (SCI) lowers the quality of patient life, restricts rehabilitative efforts and currently limited options for effective treatment are available. SCI-associated sensorimotor deprivation leads to mechanical allodynia, while sensorimotor activation has the potential to alleviate this acquired hypersensitivity. This is paralleled by maladaptive plasticity in the dorsal horn below the level of SCI. In the first funding period, we showed in contused SCI mice that treadmill training – started either acutely or delayed – specifically alleviates mechanical allodynia and spatial preference, reflecting affective measures of pain. These behavioural changes correlate with reduced sprouting of nociceptive afferents from superficial lamina into laminae III/IV, where typically non-noxious stimuli are being processed. This proposal strives to ask can structure-function alterations in SCI-related neuropathic pain in the dorsal horn of the lumbar spinal cord be linked rostrally to spinal lesion sensory (spinothalamic, lemniscal) pathway damage as well as caudally to peripheral nerve alterations? Can these alterations be manipulated by sensorimotor activation or pharmacological interventions to provide therapeutic benefit? This work will be undertaken by intersectional genetics approaches in transgenic mice as well as recruitment of patients in sensorimotor activity tracking in conjunction with spinal and peripheral MRI.

We hypothesize that a spinal cord injury leads to below level peripheral changes that induce rewiring of the dorsal horn of the lumbar spinal cord resulting in mechanical allodynia. Understanding the function of these structural rearrangements and their underlying mechanism of activation is the aim of the human-rodent tandem A06.