Injectable Nerve-Selective Cold Neurolysis for Pain Management: Sensory Neuron Modulation and Clinical Translation

We previously demonstrated that selective cold neurolysis (SCN) of the sciatic nerve, with ice slurry, leads to long-lasting analgesia in rats. To decipher the molecular signatures of analgesia, rat dorsal root ganglia (DRG) were analyzed using RNA-seq after SCN.

SCN induced an upregulation of regeneration-associated genes and concomitant changes in genes related to neuronal excitability. We explored the clinical translational potential of SCN through a single-arm, first-in-human pilot investigation involving 16 patients with chronic pain secondary to knee osteoarthritis. These results show that SCN is safe and tolerable, and associated with a 4-point reduction (p < 0.001) in pain levels, assessed through self-reported Numeric Rating Scores, which peaked at 7 days and persisted for up to 12 weeks after a single injection.