(150) - Silencing keratinocytes in a postoperative pain model

Abstract

Acute postoperative pain is experienced by the majority who undergo surgery. In addition, mechanical and thermal hyperalgesia are observed at the site of incision. Treatments for postoperative pain are suboptimal and understanding the underlying mechanism of this acute pain is vital to developing improved treatments. Previous experiments have demonstrated that in non-injured skin, hyperpolarization of keratinocytes decreases baseline mechanical and heat sensitivity. However, it is unknown if keratinocytes play a role in mediating the mechanical and thermal hyperalgesia observed in a postoperative incision model. Here, we utilized optogenetics to assess whether silencing keratinocytes by means of hyperpolarization, would reduce post-incisional heat and mechanical hyperalgesia. Transgenic mice that selectively expressed Archaerhodopsin (Arch) in keratinocyte cell membranes were used as a model. A 5 mm incision was made through the skin and underlying plantar muscle. The ipsilateral paw was exposed to amber light, to activate Arch, or blue light (control). Mechanical and heat sensitivity were measured on the ipsilateral medial hind paw, using the von Frey mechanical assay and the Hargreaves heat assay, respectively. Measurements were collected daily, including 2-hours post-incision through 7 days post-incision. Despite all animals developing significant heat and mechanical hyperalgesia following incision, there was no significant difference in post-incision hyperalgesia following the hyperpolarization of keratinocytes. However, after 15 minutes of amber light exposure, a trend in decreased heat hyperalgesia emerged in days 4, 5 and 7. The data suggest that transient silencing of keratinocytes is not sufficient to significantly decrease the sensitization experienced in this post-incision model. As pain sensed by injury to the plantar muscle may be concealing the effects of silencing keratinocytes, future studies will isolate the incision to exclusively skin. Supported by a T35 training grant from the National Heart, Lung, and Blood Institute.