Boldine Attenuates Mechanical Allodynia and Mitigates Transcriptomic Changes in a Mouse Model of Chronic Constriction Injury

Methods

Male C57BL6 mice were subjected to chronic constriction injury (CCI) to the sciatic nerve. Customized chow containing boldine or control chow was administered right after surgery. Mechanical pain responses were assessed by Von Frey filament test.

Spontaneous pain-like weight bearing behavior was measured using the dynamic weight bearing system. Spinal cords were collected at 15 days post injury and subjected to quantitative PCR and bulk RNA sequencing. Results: CCI led to ipsilateral hypersensitivity of mechanical pain responses and weight bearing deficits including reduced rearing duration, ipsilateral/contralateral weight support ratio, and ipsilateral hind paw posed duration.

Boldine treatment substantially attenuated CCI-induced mechanical allodynia, but not the weight bearing deficits. Gene expression analysis showed that boldine inhibited CCI-induced upregulation of inflammatory markers in the spinal cord. RNA sequencing analysis revealed several pain-related canonical pathways and upstream factors after CCI, and boldine treatment markedly reversed these CCI-induced transcriptomic changes.

Conclusions: In a mouse model of CCI, oral administration of boldine reduced nerve injury-induced mechanical allodynia and counter-regulated injury-associated transcriptomic changes in the spinal cord, possibly through regulating inflammation and immune responses.