Spinal Dorsal Horn Neuronal Alterations Following CFA-Induced Inflammatory Pain in Mice

The spinal dorsal horn (SDH) plays a crucial role in nociceptive processing. However, the temporal dynamics of neuronal excitability across different laminae during inflammatory pain remain incompletely understood.

Complete Freund's adjuvant (CFA) was injected into the left hindpaw to induce inflammatory pain. Spontaneous pain behaviors were evaluated using CatWalk gait analysis and weight-bearing tests, while mechanical hypersensitivity was assessed using von Frey filaments. Neuronal activation patterns were mapped using c-Fos (a protein product of the c-Fos immediate-early gene) immunolabeling across superficial and deeper laminae of the SDH. Spontaneous and mechanically-evoked neuronal discharges were recorded in vivo using multi-electrode arrays.

Spontaneous pain behaviors were most pronounced during the first 3 days post CFA injection, with mechanical hypersensitivity persisting through day 7. A marked increase in c-Fos-positive neurons was observed specifically in superficial laminae on day 1, with no significant changes detected in the deeper laminae. Spontaneous and mechanically-evoked firing rates of SDH neurons increased significantly during days 1-5 post CFA injection. Importantly, wide dynamic range (WDR) neurons exhibited the greatest increase in evoked discharge frequency, while low-threshold mechanoreceptor (LTM) neurons showed the greatest proportional increase amongst neuronal subtypes. Furthermore, both WDR and LTM neurons shifted towards a more superficial distribution.

Peripheral inflammatory pain induced distinct alterations in SDH neurons, characterized by an early increase in neuronal activities, followed by changes in the spatial distribution and proportion of WDR and LTM neurons.