Von Frey Assessment of Mechanical Sensitivity Following a Revised Sciatic Nerve Constriction Procedure in Mice

• Aadi Varshney, Biological Sciences, University of Delaware

• Austin Keeler, Biological Sciences, University of Delaware

Neuropathic pain can develop following peripheral nerve injury. This pain is commonly modeled in mice using sciatic nerve constriction (SCC), in which catgut ligatures are tied directly around the sciatic nerve. Pain-related behaviors such as mechanical hypersensitivity resulting from the SCC procedure can be assessed using electronic von Frey (eVF) testing. This assay involves the use of eVF filaments that are gradually applied to the plantar surface of the hind paw until a nocifensive response occurs. Lower paw-withdrawal thresholds indicate an increase in mechanical sensitivity. Previous SCC experiments in the Keeler Lab did not produce a consistent reduction in mechanical withdrawal threshold with eVF. An IACUC-approved revised postoperative protocol was implemented in which ketoprofen, a drug used to treat pain and inflammation, was omitted following the advice of colleagues with extensive experience using the SCC model. This pilot study assessed whether the revised SCC protocol produced detectable mechanical allodynia when compared with previous data from the original protocol. Twelve age-matched adult male mice were included across the original and revised protocol cohorts, with three sham and three SCC mice in each cohort. Mechanical withdrawal thresholds were measured in the right ipsilateral hind paw at baseline and one week following surgery. Within the revised cohort, sham mice showed minimal average change between baseline and week 1, whereas all three SCC mice demonstrated reduced withdrawal thresholds, indicating increased sensitivity to mechanical stimuli. However, the reduction in the SCC group did not reach statistical significance in the paired analysis (p = 0.3019), and the observed effect was smaller than anticipated. Previous SCC data obtained under the original postoperative protocol did not show a consistent sensitivity change. These findings suggest that the revised SCC procedure may improve detection of neuropathic mechanical hypersensitivity, but the study is still underpowered. Future studies will focus on increasing sample size and combining SCC with gonadectomies to investigate hormonal influences on chronic neuropathic pain