Capsaicin pretreatment alleviates postoperative pain and reduces primary sensory neuron Ca²⁺ activity

Abstract

After surgeries, especially thoracotomy incision, patients develop unbearable pain. Opioids are used for reducing pain but often cause serious side effects. Previously, we found that capsaicin pretreatment of the incision area alleviated spontaneous and thermal pain in a postoperative pain animal model. In the present study, we aimed to monitor primary sensory neuron Ca2+ activity in in vivo dorsal root ganglia (DRG) in a postoperative pain model using Pirt-GCaMP3 treated with capsaicin or controls. Intraplantar injection of capsaicin (0.05%) alleviated spontaneous, mechanical, and thermal postoperative pain. The Ca2+ response in in vivo DRG and in in situ spinal cord was significantly enhanced in the ipsilateral side compared to 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 alleviates postoperative pain by suppressing Ca2+ response due to degeneration of primary sensory nerve fibers in the skin.

Prdm12 modulates pain-related behavior by remodeling gene expression in mature nociceptors

“…Indeed, capsaicin can be used as analgesic and has been shown to reduce lesion or inflammation-induced pain by triggering receptor endocytosis 48 , 58 or nerve retraction. 17 , 22 , 43 It could also be because of posttranscriptional modifications of TRPV1, its activity being modulated by kinases such as calmodulin-dependent protein kinase (CaMKII), protein kinase C (PKC) and protein kinase A (PKA), and phosphatases (calcineurin) as well as lipids such as PIP2, 46 themselves regulated by G protein-coupled membrane receptors. Nerve growth factor plays a role in the sensitization of nociceptors via different mechanisms, including through the control of trafficking of TRPV1 channels to the plasma membrane.…”