Suppression of GABAergic transmission in the spinal dorsal horn induces pain-related behaviour in a chicken model of spina bifida

Abstract

Spina bifida aperta (SBA), one of the most common congenital malformations, causes various neurological disorders. Pain is a common complaint of patients with SBA. However, little is known about the neuropathology of SBA-related pain. Because loss of g-aminobutyric acid GABAergic neurons in the spinal cord dorsal horn is associated with pain, we hypothesised the existence of crosstalk between SBA-related pain and alterations in GABAergic transmission in the spinal cord. Therefore, we investigated the kinetics of GABAergic transmission in the spinal cord dorsal horn in a chicken model of SBA. Neonatal chicks with SBA exhibited various pain-like behaviours, such as an increased number of vocalisations with elevated intensity (loudness) and frequency (pitch), reduced mobility, difficulty with locomotion, and escape reactions. Furthermore, the chicks with SBA did not respond to standard toe-pinching, indicating disruption of the spinal cord sensorimotor networks. These behavioural observations were concomitant with loss of GABAergic transmission in the spinal cord dorsal horn. We also found apoptosis of GABAergic neurons in the superficial dorsal horn in the early neonatal period, although cellular abnormalisation and propagation of neuro­degenerative signals were evident at middle to advanced gestational stages. In conclusion, ablation of GABAergic neurons induced alterations in spinal cord neuronal networks, providing novel insights into the pathophysiology of SBA-related pain-like complications.

Keywords

• spina bifida
• chicken model
• pain-related behaviour
• gabaergic transmission
• apoptosis.