Background and Aims: Spontaneous pain is thought to be driven by ectopic activity in damaged sensory afferent neurones. In this study we investigate the role of IL6 in engaging persistent pain mechanisms by in vivo electrophysiological recordings and behavioural assessment to investigate its involvement in spontaneous pain. 

Methods: Rats were implanted with osmotic minipumps filled with either 0.9% saline or IL6 inserted intrathecally at T10 delivering IL-6 (2g/day) or saline for 3 days. Additionally, rats with spinal nerve ligation (SNL) received either anti-IL-6 antibody tocilizumab, 8mg/kg or saline in a single i.p injection. Neural recordings and behavioural testing were carried out at day 3 post-implant/SNL. Behavioural testing continued to day 7 using the dynamic plantar aesthesiometer. 

Results: Intrathecal IL6 induced spontaneous firing of sensory afferents that closely mimicked the spontaneous activity seen following SNL. In IL6-treated rats, spontaneously active fibres were found in 76±8% of strands (mean±SEM). By comparison, 87±5% of strands in SNL rats contained ectopically active units. In SNL rats treated with tocilizumab, 68±1% strands were active. In behavioural studies, animals receiving IL6 intrathecally showed significant reduction of 20-33% in paw withdrawal thresholds to mechanical stimulation as compared to controls. Tocilizumab significantly attenuated the post-SNL increase in mechanical sensitivity for up to 7 days after treatment with a 21-35% improvement in the ipsilateral paw withdrawal threshold at day 2 to day 7 following injury, compared to control.

Conclusions: This study has established the involvement of IL6 in the spontaneous firing of sensory fibres and mechanical hypersensitivity in rats following nerve injury.

INTERLEUKIN -6 PROMOTES SPONTANEOUS FIRING OF SENSORY AFFERENT FIBRES IN THE RAT