Abstract
Spasticity, a common complication after spinal cord injury (SCI), is frequently accompanied by chronic pain. The physiological origin of this pain (critical to its treatment) remains unknown, although spastic motor dysfunction has been related to the hyperexcitability of motoneurons and to changes in spinal sensory processing. Here we show that the pain mechanism involves changes in sensory circuits of the dorsal horn (DH) where nociceptive inputs integrate for pain processing. Spasticity is associated with the DH hyperexcitability resulting from an increase in excitation and disinhibition occurring in two respective types of sensory interneurons. In the tonic-firing inhibitory lamina II interneurons, glutamatergic drive was reduced while glycinergic inhibition was potentiated. In contrast, excitatory drive was boosted to the adapting-firing excitatory lamina II interneurons while GABAergic and glycinergic inhibition were reduced. Thus, increased activity of excitatory DH interneurons coupled with the reduced excitability of inhibitory DH interneurons post-SCI could provide a neurophysiological mechanism of central sensitization and chronic pain associated with spasticity.
Highlights
Spasticity is one of the most severe complications after spinal cord injury (SCI) or trauma, representing chronic motor deficit attributed with muscle spasms, hyperreflexia and impaired locomotion, which develops in up to 80% of the SCI patients[1,2,3,4]
The ratio of the H- to the M-waves was markedly increased on the ipsilateral side in the SCI-injured rats at ~1 month postSCI
The overall balance between excitation and inhibition within the dorsal horn (DH) was re-directed from driving of inhibitory interneurons in control to boosting of excitatory interneurons post-SCI (Fig. 7f). This is the first study of central mechanisms underlying chronic pain associated with spasticity that reveals the SCI-induced shifts in neuronal excitation and inhibition resulted in the DH circuit hyperexcitability
Summary
Spasticity is one of the most severe complications after spinal cord injury (SCI) or trauma, representing chronic motor deficit attributed with muscle spasms, hyperreflexia and impaired locomotion, which develops in up to 80% of the SCI patients[1,2,3,4]. Chronic pain often progressively develops within months after SCI and could expand to severe and unceasing pain syndrome either rapidly or through various patterns of delayed appearance[5, 6]. We test the hypothesis that the pain mechanism involves changes in the DH circuitry with the key question how the overall hyperexcitability post-SCI relates to a high heterogeneity of DH interneurons. To address this we combined electrophysiology with behavioural testing in experimental modelling of SCI in rats. Post-SCI – increased excitability of excitatory lamina II interneurons and suppressed activity of inhibitory lamina II interneurons – that provide novel insights into neurophysiological mechanisms underlying chronic pain
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