Abstract

Introduction:Chronic pain is present in approximately 20% of the population and is a major burden to the healthcare system. Approximately 30% to 40% of these patients report neuropathic pain. Neuropathic pain is defined as pain caused by injury or disease of the somatosensory nervous system. Current available treatments for neuropathic pain have limited efficacy and substantial side effects.Objective:To address the need for more effective and safer treatments for neuropathic pain, this study aimed to test whether boldine, a naturally occurring alkaloid, could attenuate neuropathic pain in a murine model of spared nerve injury (SNI).Methods:Von Frey filament test, hot/cold plate test, and dynamic weight-bearing test were used to assess pain phenotypes and functional outcomes after SNI. Multiplex enzyme-linked immunosorbent assay, quantitative PCR, and immunostainings were performed to evaluate cellular and molecular changes after boldine treatment.Results:Oral administration of boldine at 50 mg/kg body weight/day resulted in significant reduction of SNI-induced mechanical and thermal hypersensitivities. Functional outcome measurements showed that boldine corrected SNI-induced weight-bearing deficits. Boldine significantly inhibited SNI-induced elevation of some pain-related inflammatory cytokines/chemokines in the serum. Immunofluorescence studies revealed that boldine reduced the number of reactive astrocytes and inhibited microglia activation in the lumbar spinal cord. In vitro studies showed that boldine inhibited the lipopolysaccharide-induced elevation of inflammatory markers in BV-2 microglial cells.Conclusion:Our findings suggest that boldine may be a promising therapeutic candidate for the treatment of neuropathic pain, possibly through inhibition of glia activation and neuroinflammation.