Formoterol alters chemokine expression and ameliorates pain behaviors after moderate spinal cord injury in female mice

Secondary spinal cord injury (SCI) is characterized by increased cytokines and chemokines at the site of injury that have been associated with the development of neuropathic pain. Nearly 80% of SCI patients report suffering from chronic pain, which is poorly managed with available analgesics. While treatment with the US Food and Drug Administration-approved b2-adrenergic receptor agonist formoterol improves various aspects of recovery post-SCI in vivo, its effects on cytokines, chemokines, and neuropathic pain remain unknown. Female mice were subjected to moderate (60 kilodynes [kdyn]) or severe (80 kdyn) SCI followed by daily treatment with vehicle or formoterol (0.3 mg/kg, i.p.) beginning 8 hours after injury. The expression of proinflammatory cytokines/chemokines, such as interferon gamma-induced protein 10, macrophage inflammatory protein 1a, monocyte chemoattractant protein 1, B-cell attracting chemokine 1, and nuclear factor kappa-light-chain-enhancer of activated B-cells, was increased in the injury site of vehicle-treated mice 24 hours post-SCI, which was ameliorated with formoterol treatment, regardless of injury severity. Thermal hyperalgesia and mechanical allodynia, as measured by Hargreaves infrared apparatus and von Frey filaments, respectively, were assessed prior to SCI and then weekly beginning 21 days post-injury (DPI). While all injured mice exhibited decreased withdrawal latency following thermal stimulation compared with baseline, formoterol treatment reduced this response ~15% by 35 DPI. Vehicle-treated mice displayed significant mechanical allodynia, as evidenced by a 55% decrease in withdrawal threshold from baseline. In contrast, mice treated with formoterol maintained a consistent withdrawal time at all times tested. These data indicate that formoterol reduces inflammation post-SCI, likely contributing to mitigation of neuropathic pain and further supporting the therapeutic potential of this treatment strategy.