Reduced Pain Responses With a Digital Automatic Syringe: Behavioral and Molecular Evidence in a Rodent Formalin Model

Manual syringe injections often produce variable pain responses due to inconsistent injection pressure and speed, complicating both clinical procedures and experimental outcomes. The digital automatic syringe, I-ject™, was developed to provide controlled, reproducible injections and thereby reduce injection-associated pain.

Using a formalin-induced acute pain model in rats, we compared nociceptive behavioral and molecular responses between injections delivered by a conventional manual syringe versus the I-ject™ automatic syringe. Pain-related behaviors, limping and licking of the injected paw, were recorded for 60 min. After behavioral observation, spinal cord tissue was collected for quantitative real-time PCR analysis of pain-related genes.

Rats injected with the I-ject™ automatic syringe exhibited a 30.6% reduction in limping and a 66.0% reduction in licking frequency within the 15 min after formalin injection, compared to those injected with a manual syringe (p<0.05). Expression of examined pain-marker genes was significantly lower in the automatic syringe group than in the manual syringe group. Notably, c-fos and GFAP mRNA levels were reduced by 29.7% and 81.8%, respectively. Similar downregulation trends were observed for Oprl1, Htr2a, and Oprm1, indicating that the automatic injection attenuated both neuronal and glial activation associated with pain.

The I-ject™ automatic syringe markedly reduced both behavioral signs of pain and molecular markers of nociceptive activation in this rodent formalin pain model. These findings support the potential of this digital automatic injection system as a safer and more consistent alternative to conventional manual syringes in both preclinical research and clinical settings.