Previous studies have shown that infiltration of
capsaicin into the surgical site can prevent incision-induced spontaneous
pain like behaviors and heat
hyperalgesia. In the present study, we aimed to monitor primary sensory neuron Ca2+ activity in the intact dorsal root ganglia (DRG) using Pirt-GCaMP3 male and female mice pretreated with
capsaicin or vehicle before the plantar incision. Intraplantar injection of
capsaicin (0.05%) significantly attenuated spontaneous
pain, mechanical, and heat
hypersensitivity after plantar incision. The Ca2+ response in in vivo DRG and in in situ spinal cord was significantly enhanced in the ipsilateral side compared with contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in
capsaicin-pretreated animals detected by immunohistochemistry and
placental alkaline phosphatase (PLAP) staining. Thus,
capsaicin pretreatment attenuates incisional
pain by suppressing Ca2+ response because of degeneration of primary sensory nerve fibers in the skin.SIGNIFICANCE STATEMENT Postoperative surgery
pain is a major health and economic problem worldwide with ∼235 million major
surgical procedures annually. Approximately 50% of these patients report uncontrolled or poorly controlled
postoperative pain. However, mechanistic studies of postoperative surgery
pain in primary sensory neurons have been limited to in vitro models or small numbers of neurons. Using an innovative, distinctive, and interdisciplinary in vivo populational dorsal root ganglia (DRG) imaging (>1800 neurons/DRG) approach, we revealed increased DRG neuronal Ca2+ activity from
postoperative pain mouse model. This indicates widespread DRG primary sensory neuron plasticity. Increased neuronal Ca2+ activity occurs among various sizes of neurons but mostly in small-diameter and medium-diameter nociceptors.
Capsaicin pretreatment as a therapeutic option significantly attenuates Ca2+ activity and
postoperative pain.