Baclofen modulates the immune response after spinal cord injury with locomotor benefits

Br J Pharmacol. 2025 Jan 22. doi: 10.1111/bph.17438. Online ahead of print.

Abstract

Background and purpose: Spinal cord injury (SCI) is a neurological condition that affects motor and sensory functions below the injury site. The consequences of SCI are devastating for the patients, and although significant efforts have been done in the last years, there is no effective therapy. Baclofen has emerged in the last few years as an interesting drug in the SCI field. Already used in the SCI clinical setting to control spasticity, baclofen has shown important impact on SCI recovery in animal models, such as lampreys and mice.

Experimental approach and key results: Herein, we proposed to go deeper into baclofen's mechanism of action and to study its role on the modulation of the immune response after SCI, a major process associated with the severeness of the lesion. Using a SCI compression mice model, we confirmed that baclofen leads to higher locomotor performance, but only at 1 mg·kg-1 and not in higher concentrations, as 5 mg·kg-1. Moreover, we found that baclofen at 1 mg·kg-1 can strongly modulate the immune response after SCI at local, systemic and peripheric levels. This is interesting and intriguingly at the same time, since now, additional studies should be performed to understand if the modulation of the immune response is the responsible for the locomotor outcomes observed on Baclofen treated animals.

Conclusion and implications: Our findings showed, for the first time, that baclofen can modulate the immune response after SCI, becoming a relevant drug in the field of the immunomodulators.

Keywords: baclofen; functional response; inflammatory response; microglia; spinal cord injury.