In Vivo Calcium Imaging Visualizes Incision-Induced Primary Afferent Sensitization and Its Amelioration by Capsaicin Pretreatment.

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.

Gait and plantar sensation changes following massage and textured insole application in patients after anterior cruciate ligament reconstruction.

BACKGROUND: Gait impairments following anterior cruciate ligament reconstruction (ACLR) may contribute to reinjury or future osteoarthritis development. Recently, plantar cutaneous sensation deficits have been reported post-ACLR. These sensory deficits may influence gait and represent a mechanism through which to improve gait. RESEARCH QUESTION: Can established sensory interventions change sensation and gait in patients after ACLR and compared to healthy adults? METHODS: Twenty-two adults (n = 11 post-ACLR, age:20.5 ±â€¯1.9years, body mass index[BMI]:24.5 ±â€¯3.6 kg/m2; n = 11 healthy, age:20.7 ±â€¯1.4years, BMI:23.3 ±â€¯2.7 kg/m2) completed two sessions separated by 48 h. Gait and plantar cutaneous sensation were assessed pre- and post-intervention (massage or textured insoles). Gait analysis was completed using 3D motion capture at 1.4 m/s ±â€¯5% and standard inverse dynamics analysis. Plantar cutaneous sensation was assessed using Semmes Weinstein Monofilaments with a 4-2-1 stepping algorithm at the plantar aspect of the first metatarsal head, base of the fifth metatarsal, and lateral and medial malleoli. Plantar massage was a 5-minute massage to both feet. Textured insoles (coarse grit sandpaper) were worn while walking. Biomechanical data were assessed via mixed-models, repeated measures ANOVAs and 90 % confidence intervals. Wilcoxon Signed Rank tests and Mann-Whitney U tests evaluated plantar cutaneous sensation within and between groups, respectively. RESULTS: Knee adduction moment was lower in the ACLR versus the contralateral limb pre-massage. The vGRF was lower during the first half of stance but greater during the second half of stance in the ACLR versus the control group post-massage. Massage improved ACLR limb sensation over the first metatarsal head (P = 0.042) and medial malleolus (P = 0.027). Textured insole application improved ACLR limb sensation over the first (P = 0.043) and fifth (P = 0.027) metatarsals and medial malleolus (P = 0.028). SIGNIFICANCE: Plantar massage and textured insoles improved plantar cutaneous sensation in the ACLR limb. Neither intervention influenced gait. Improving plantar sensation may be beneficial for patients after ACLR; however, sensory interventions to improve gait are necessary.

Surgical incision induces learning impairment in mice partially through inhibition of the brain-derived neurotrophic factor signaling pathway in the hippocampus and amygdala.

Surgical incision-induced nociception contributes to the occurrence of postoperative cognitive dysfunction. However, the exact mechanisms involved remain unclear. Brain-derived neurotrophic factor (BDNF) has been demonstrated to improve fear learning ability. In addition, BDNF expression is influenced by the peripheral nociceptive stimulation. Therefore, we hypothesized that surgical incision-induced nociception may cause learning impairment by inhibiting the BDNF/tropomyosin-related kinase B (TrkB) signaling pathway. The fear conditioning test, enzyme-linked immunosorbent assay, and Western blot analyses were used to confirm our hypothesis and determine the effect of a plantar incision on the fear learning and the BDNF/TrkB signaling pathway in the hippocampus and amygdala. The freezing times in the context test and the tone test were decreased after the plantar incision. A eutectic mixture of local anesthetics attenuated plantar incision-induced postoperative pain and fear learning impairment. ANA-12, a selective TrkB antagonist, abolished the improvement in fear learning and the activation of the BDNF signaling pathway induced by eutectic mixture of local anesthetics. Based on these results, surgical incision-induced postoperative pain, which was attenuated by postoperative analgesia, caused learning impairment in mice partially by inhibiting the BDNF signaling pathway. These findings provide insights into the mechanism underlying surgical incision-induced postoperative cognitive function impairment.