Evidence of silent nociceptor activation during the formalin test in rats

In male and female rats, C-mechano-insensitive (C-Mi) nociceptors show ongoing activity in both formalin test phases, with 33.3% in phase 1 and 31.0% in phase 2.

• Why it matters: Silent C-Mi nociceptors are linked to chronic pain, yet they are often missed in preclinical models because they lack mechanical sensitivity. The formalin test’s phase 2 depends on disputed peripheral drive, so C-Mi behavior was unclear.
• What they did: Using multi-contact microneurography from the saphenous nerve, the authors applied an activity dependent slowing protocol to classify C-fibres as C-M or C-Mi. They then measured formalin- (2.5%) versus saline-evoked activity across phase 1 and phase 2.
• The result: ADS-classified C-Mi nociceptors were active in both phases (n=18 and n=16), while there was no evidence that formalin mechanically sensitises C-Mi nociceptors or changes ADS profiles. This suggests ongoing C-Mi activity may contribute to phase 2 sensitisation in the formalin assay.

AI summary of the abstract · may contain errors · not medical advice · read the paper.