Oral Boldine Administration Attenuates Glia Activation and Prevents Neuropathic Pain in a Murine Spared Nerve Injury Model

Pan, J.; Duarte, Y.; Chow, C.; Toro, C. A.; Saez, J. C.; Cardozo, C. P.; Zhao, W.

doi:10.1101/2024.11.05.622128

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bioRxiv · 10.1101/2024.11.05.622128

Oral Boldine Administration Attenuates Glia Activation and Prevents Neuropathic Pain in a Murine Spared Nerve Injury Model

Pan, J.·Duarte, Y.·Chow, C.·Toro, C. A.·Saez, J. C.·Cardozo, C. P.·Zhao, W.

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Abstract

BackgroundChronic pain is present in about 20% of the population and is a major burden to the health care system. About 30-40% 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. MethodsTo 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). Von Frey filament test, hot/cold plate test and dynamic weight bearing test were used to assess pain phenotypes following SNI. ResultsWe found that boldine inhibited the lipopolysaccharide-induced overexpression of inflammatory markers in BV-2 microglial cells. Oral administration of boldine at 50 mg/kg body weight/day resulted in significant reduction of SNI-induced mechanical and thermal hypersensitivity. Boldine also corrected SNI-induced weight bearing deficits, which are an indication of spontaneous pain. Boldine significantly inhibited SNI-induced peripheral inflammation as indicated by reduced levels of inflammatory cytokines/chemokines in the serum. Immunofluorescence studies revealed that boldine reduced the number of reactive astrocytes and inhibited microglia activation in lumbar spinal cord. ConclusionOur findings suggest that boldine may be a promising therapeutic candidate for the treatment of neuropathic pain, possibly through inhibition of glia activation and neuroinflammation.

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Pan, J., Duarte, Y., Chow, C., Toro, C. A., Saez, J. C., Cardozo, C. P., Zhao, W.. 2024-11-05. Oral Boldine Administration Attenuates Glia Activation and Prevents Neuropathic Pain in a Murine Spared Nerve Injury Model. https://doi.org/10.1101/2024.11.05.622128

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