Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains.

IF 5.9 2区 医学 Q2 CELL BIOLOGY Neural Regeneration Research Pub Date : 2025-09-01 Epub Date: 2024-06-26 DOI:10.4103/NRR.NRR-D-23-01846
Liwen Zhou, Karthik Venkudusamy, Emily A Hibbard, Yessenia Montoya, Alexa Olivarez, Cathy Z Yang, Adelaide Leung, Varun Gokhale, Guhan Periyasamy, Zeal Pathak, Dale R Sengelaub, George D Bittner
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Abstract

JOURNAL/nrgr/04.03/01300535-202509000-00028/figure1/v/2024-11-05T132919Z/r/image-tiff Successful polyethylene glycol fusion (PEG-fusion) of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to: (1) rapidly restore electrophysiological continuity; (2) prevent distal Wallerian Degeneration and maintain their myelin sheaths; (3) promote primarily motor, voluntary behavioral recoveries as assessed by the Sciatic Functional Index; and, (4) rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex (e.g., toe twitch) or voluntary behaviors. The preceding companion paper describes sensory terminal field reorganization following PEG-fusion repair of sciatic nerve transections or ablations; however, sensory behavioral recovery has not been explicitly explored following PEG-fusion repair. In the current study, we confirmed the success of PEG-fusion surgeries according to criteria (1-3) above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats. Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws. Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections. Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex. Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats. Following sciatic transection, all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury. However, PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats. Furthermore, PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recovery compared with those without Sciatic Functional Index recovery, suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries. This correlation was independent of the sex or strain of the rat. Furthermore, our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths. No chronic hypersensitivity developed in any rat up to 12 weeks. All these data suggest that PEG-fusion repair of transection peripheral nerve injuries could have important clinical benefits.

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聚乙二醇融合修复切断的坐骨神经可加速不同品系雌雄大鼠痛觉知觉的恢复。
摘要:据报道,在外周神经损伤后对切断的轴突进行聚乙二醇融合(PEG-融合)是成功的:(1)迅速恢复电生理连续性;(2)防止远端沃勒里变性并保持其髓鞘;(3)根据坐骨神经功能指数评估,主要促进运动和自主行为的恢复;以及(4)以多种可能的组合迅速产生正确和不正确的连接,从而快速、广泛地恢复外周神经系统/中枢神经系统的功能连接以及反射(如脚趾抽动)或自主行为。前一篇论文介绍了坐骨神经横断或消融的 PEG 融合修复术后感觉末梢场重组的情况,但尚未明确探讨 PEG 融合修复术后感觉行为恢复的情况。在本研究中,我们根据上述标准(1-3)确认了 PEG 融合手术的成功,并更广泛地研究了 PEG 融合是否能增强雄性和雌性外交 Sprague-Dawley 大鼠和近交 Lewis 大鼠坐骨神经横断后的机械痛觉恢复。机械痛觉反应是通过使用后爪背侧和跖中部的 von Frey 细丝测量抽离阈值来评估的。在评估坐骨神经横断后的机械痛觉敏感性时,背侧 von Frey 灯丝测试比跖侧 von Frey 灯丝测试更可靠。坐骨神经介导的外侧背侧区域的基线牵拉阈值在不同应变之间存在显著差异,但在性别上没有差异。慢性未手术大鼠和 Sham 手术大鼠的牵拉阈值与基线相比没有显著变化。坐骨神经横断后,所有大鼠对损伤同侧后爪外侧背区的刺激都表现出严重的低敏感性。然而,与阴性对照组大鼠相比,融合 PEG 的大鼠恢复到基线戒断阈值的时间明显更早。此外,与坐骨神经功能指数未恢复的大鼠相比,术后 4 周或 4 周后坐骨神经功能指数评分明显改善的 PEG 融合大鼠表现出更早的 von Frey 细丝恢复,这表明成功的 pPEG 融合与运动主导型和感觉主导型行为恢复之间存在相关性。这种相关性与大鼠的性别或品系无关。此外,我们的数据还显示,von Frey丝感觉加速恢复到基线完全是由于PEG融合坐骨神经而不是隐神经侧支生长所致。在长达 12 周的时间里,没有大鼠出现慢性过敏反应。所有这些数据表明,PEG-融合修复横断周围神经损伤可能会带来重要的临床益处。
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来源期刊
Neural Regeneration Research
Neural Regeneration Research CELL BIOLOGY-NEUROSCIENCES
CiteScore
8.00
自引率
9.80%
发文量
515
审稿时长
1.0 months
期刊介绍: Neural Regeneration Research (NRR) is the Open Access journal specializing in neural regeneration and indexed by SCI-E and PubMed. The journal is committed to publishing articles on basic pathobiology of injury, repair and protection to the nervous system, while considering preclinical and clinical trials targeted at improving traumatically injuried patients and patients with neurodegenerative diseases.
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