Accumulation of ß-aminoisobutyric acid mediates hyperalgesia in ovariectomized mice through Mas-related G protein-coupled receptor D signaling.

Hyperalgesia is typified by reduced pain thresholds and heightened responses to painful stimuli, with a notable prevalence in menopausal women, but the underlying mechanisms are far from understood. ß-Aminoisobutyric acid (BAIBA), a product of valine and thymine catabolism, has been reported to be a novel ligand of the Mas-related G protein coupled receptor D (MrgprD), which mediates pain and hyperalgesia. Here, we established a hyperalgesia model in 8-week-old female mice through ovariectomy (OVX). A significant increase in BAIBA plasma level was observed and was associated with decline of mechanical withdrawal threshold, thermal and cold withdrawal latency in mice after 6 weeks of OVX surgery. Increased expression of MrgprD in dorsal root ganglion (DRG) was shown in OVX mice compared to Sham mice. Interestingly, chronic loading with BAIBA not only exacerbated hyperalgesia in OVX mice, but also induced hyperalgesia in gonadally intact female mice. BAIBA supplementation also upregulated the MrgprD expression in DRG of both OVX and intact female mice, and enhanced the excitability of DRG neurons in vitro. Knockout of MrgprD markedly suppressed the effects of BAIBA on hyperalgesia and excitability of DRG neurons. Collectively, our data suggest the involvement of BAIBA in the development of hyperalgesia via MrgprD-dependent pathway, and illuminate the mechanisms underlying hyperalgesia in menopausal women.

Reconstruction of Large Area of Deep Wound in the Foot and Ankle with Chimeric Anterolateral Thigh Perforator Flap.

OBJECTIVE: To evaluate the clinical application and surgical efficacy of the chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap for the reconstruction of the large area of deep wound in foot and ankle. METHODS: Clinical data of 32 cases who underwent chimeric anterolateral thigh perforator flap to repair the large area of deep wound of the foot and ankle from January 2015 to December 2018 were retrospectively analyzed. The sizes of the defects ranged from 18 cm × 10 cm to 35 cm × 20 cm, with exposed tendon and bone and/or partial defects and necrosis, contaminations, accompanied by different degrees of infection. Following the radical debridement and VSD, chimeric anterolateral thigh perforator flap was employed to repair the deep wounds according to the position, site and deep-tissue injury of the soft-tissue defects. The skin flap and muscle flap were fanned out on the wound, and single- or two-staged split-thickness skin grafting was performed on the muscle flap. The operation time and blood loss were recorded. The survival and healing conditions of the operational site with chimeric anterolateral thigh perforator flap were evaluated post-operationally. Complications at both recipient site and donor site were carefully recorded. RESULTS: The mean time of the operation was 325.5 min and average blood loss was 424.8 mL. Among the 32 cases, two cases developed vascular crisis, which were alleviated with intensive investigation and treatment; Four cases suffered from partial necrosis of the flap or skin graft on the muscle flap or on the residual local wound, which were improved after treatment of further dressing change and skin grafting. Another four cases experienced post-traumatic osteomyelitis accompanied by bone defect were treated with simple bone grafting or Mesquelet bone grafting at 6-8 months after wound healing. Postoperatively, the wounds were properly healed, and the infection was effectively controlled without sinus tract forming. Overall, all 32 cases received satisfactory efficacy, without influencing subsequent functional reconstruction, and observed infection during the 12-36 months post-operational follow-up. CONCLUSION: The chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap provides an effective and relative safe procedure for the repair of a large area of deep wound in the foot and ankle, particularly with irregular defect or deep dead space.

A neglected problem in the utilization of free anterolateral thigh flap toward reconstructing complicated wounds of extremities: the obliteration of deep dead space.

BACKGROUND: Deep dead space may be thought as an independent risk factor of the poor infection control after flap reconstruction in complex limb wounds. But it can be easily neglected. The conventional skin flap and musculocutaneous flap are difficult to obliterate the deep dead space in irregular shape effectively. It was investigated that the clinical application of chimeric anterolateral thigh perforator flap in the treatment of complex wounds complicated with deep dead space of the extremities in the paper. METHODS: Fifty-six cases complicated with deep dead space wounds were registered in group. Following thorough debridement and treatment with VSD, the granulation tissues grew with well-controlled infection. And then the chimeric anterolateral thigh perforator flap was used to obliterate the deep dead space and repair the wounds. The postoperative flap survival and infection conditions were evaluated. RESULTS: Overall, the infection was effectively controlled, without persistent exudation or sinus tract formation after wound healing. While 5 cases lost to follow-up, the remaining 51 cases were followed up until 15 months on average. Generally, the affected extremities recovered satisfactorily with normal appearances and texture of the flaps, along with normal functions. Importantly, no recurrence of infection was observed. CONCLUSION: During the grafting of chimeric perforator flap pedicled with lateral thigh muscle flap, the muscle flap is recommended to obliterate the deep dead space while the skin flap is being used to cover the wound. The combination of these two technologies performed well in the repair and reconstruction of the complex wounds of the extremities, possessing potential for broader clinical application.