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Effect of Gabapentin Administered With Prednisolone, Ciclosporin or a Placebo on Clinical Outcomes and Motor Activity in Cats With Atopic Skin Syndrome: A Prospective, Blinded, Placebo- Controlled Study
加巴喷丁联合泼尼松龙、环孢素或安慰剂对患有特应性皮肤综合征的猫的临床症状及运动活动的影响：一项前瞻性、双盲、安慰剂对照研究
作者：Jeanne Morency Andrea Gonzales Jason Ross Maxim Moreau | Jean-Pierre Pelletier Colombe Otis Frédéric Sauvé
翻译：王帆
ABSTRACT
摘要
Background: Gabapentin reportedly decreases central sensitisation, a disorder associated with chronic pruritus in humans, although this is not well documented in cats. Its combined use with the standard antipruritic therapy for feline atopic skin syn drome (FASS) is not yet described.
Objectives: To evaluate the impact of prednisolone, ciclosporin or placebo, with or without gabapentin, on lesional scores and actimetry in FASS cats.
Animals: Twenty- six cats from a laboratory colony with naturally acquired FASS.
Methods and Materials: Following a 12- week washout period, cats were allocated to one of three groups: prednisolone (1 mg/ kg, n = 9), ciclosporin (7 mg/kg, n = 8) and placebo (Avicel, n = 9). Treatments were administered orally, once daily for 5 weeks (Week [W]0 to W4), then combined with gabapentin (10–15 mg/kg) for another 3 weeks. The Feline Dermatitis Extent and Severity Index (FeDESI) was assessed at baseline and W2, W4 and W7. Actimetry was recorded and analysed over weekend (WE) time points. A repeated- measures generalised mixed model was applied using the zero- inflated negative binomial (FeDESI) or log- normal (actimetry) distribution (α = 0.05).
Results: Prednisolone alone significantly improved FeDESI (p = 0.008), while ciclosporin required the addition of gabapentin to achieve a significant effect (p < 0.034). Gabapentin decreased FeDESI scores in all groups (p < 0.001) and demonstrated the high est incidence rate ratio (2.59) compared to placebo. Improvements in FeDESI were associated with significant (corresponding in intensity) decreases in motor activity.
Conclusions and Clinical Relevance: Gabapentin, particularly when combined with prednisolone or ciclosporin, may reduce lesional score and actimetry- assessed itch in FASS cats, suggesting a potential central sensitisation in some cats.
背景：加巴喷丁据报道能够减轻中枢敏化现象，这是一种与人类慢性瘙痒症相关的病症，不过在猫上尚未有明确的文献记载。其与用于治疗猫特应性皮肤综合征（FASS）的标准抗瘙痒疗法的联合使用尚未有相关描述。
目的：评估泼尼松龙、环孢素或安慰剂（与加巴喷丁联合使用或单独使用）对患有 FASS 猫的病变评分和活动度测量值的影响。
动物：来自一个实验室群居的猫群，这些猫是自然感染 FASS 。
方法与材料：在 12 周的洗脱期后，将猫分配到三个组中：泼尼松龙组（1 毫克/千克，n = 9）、环孢素组（7 毫克/千克，n = 8）和安慰剂组（Avicel，n = 9）。治疗采用口服方式，每日一次，持续 5 周（第 0 周W0至第 4 周W4），然后与加巴喷丁（10 - 15 毫克/千克）另外联合使用 3 周。在基线、W2 、W4和W7评估猫的皮炎范围和严重程度指数（FeDESI）。记录并分析周末（WE）时间点的活动度测量值。采用重复测量广义混合模型，使用零膨胀负二项式（FeDESI）或对数正态（活动度测量值）分布（α = 0.05）。
结果：单独使用泼尼松龙显著改善了 FeDESI 评分（p = 0.008），而环孢素则需要添加加巴喷丁才能达到显著效果（p < 0.034）。加巴喷丁在所有组中均降低了 FeDESI 评分（p < 0.001），并且与安慰剂相比，其发生率比值最高（2.59），显示出显著优势。FeDESI 评分的改善与运动活动的显著（强度相当）降低相关。
结论及临床意义：加巴喷丁，尤其是与泼尼松龙或环孢素联合使用时，可能降低 FASS 猫的病变评分和通过动作计数评估的瘙痒程度，这表明某些猫可能存在中枢敏化现象。
Keywords: anti- hyperalgesic | feline | gabapentinoid | immune modulation | itch | pruritus
关键词：抗痛觉过敏|猫|加巴喷丁素|免疫调节|瘙痒|瘙痒
1 | Introduction
1介绍
Feline atopic skin syndrome (FASS) is a chronic inflamma tory skin disease of the cat, with pruritus as its cornerstone. Four characteristic reaction patterns are associated with this condition: miliary dermatitis, self- induced alopecia, face, head and neck pruritus and lesions of the eosinophilic granuloma complex. These patterns, typical in FASS, are not an exclusive manifestation of this syndrome. Therefore, it is essential to rule out other clinically indistinguishable aetiologies, such as food allergy or flea bite hypersensitivity, before diagnosis. It is noteworthy that several challenges arise with this pathology, in cluding the cat's ability to conceal pruritus-related behaviours, difficulty in administering medication and the limited available effective antipruritic therapies.
猫特应性皮肤综合征（FASS）是一种猫的慢性炎性皮肤病，其主要症状为瘙痒。这种病症与之相关的四种典型反应模式为：粟粒性皮炎、自损性脱毛、头面颈部瘙痒以及嗜酸性肉芽肿复合物的病变。这些模式在 FASS 中较为常见，但并非该综合征的唯一表现形式。因此，在诊断之前，必须排除其他临床表现相似的病因，如食物过敏或跳蚤叮咬过敏等。值得注意的是，这种病理状况存在一些挑战，包括猫能够掩饰与瘙痒相关的行为、给药的困难以及可用的有效止痒疗法有限等。
The latter point is relevant, as the aetiopathogenesis of FASS is not fully elucidated. A recent study described a systemic upregulation of cytokines associated with a molecular and cel lular inflammatory response along with a complex network of chemokines and growth factors in FASS cats, while an other study showed no evidence of elevated circulating immune markers in feline atopic syndrome. Consequently, current treatments are not highly specific. In Canada, the only approved systemic medication for FASS is ciclosporin, though other standard treatments are commonly used. Notably, glucocorticoids or allergen- specific immunotherapy (ASIT) are used, each associated with potential adverse effects, financial considerations or lack of patient tolerability and compliance. Assessing ASIT efficacy in FASS also is challenging, which may contribute to the issues encountered during therapy. Other therapies, such as oclacitinib, maropitant, essential fatty acids and oral H1-receptor blocking antihistamines, have been suggested, although there is limited evidence of their efficacy in FASS cats.
后一点具有相关性，因为 FASS 的病因机制尚未完全阐明。最近的一项研究描述了 FASS 猫体内与分子和细胞炎症反应相关的细胞因子出现系统性上调，同时还有复杂的趋化因子和生长因子网络。而另一项研究则表明，过敏性综合征患猫的循环免疫标志物没有升高。因此，目前的治疗方法并不具有高度特异性。在加拿大，唯一获批用于 FASS 的全身性药物是环孢素，不过其他标准治疗方法也常被使用。值得注意的是，糖皮质激素或过敏原特异性免疫疗法（ASIT）被使用，但每种方法都伴随着潜在的不良反应、经济因素或患猫耐受性和依从性的缺乏。评估 ASIT 在 FASS 中的疗效也具有挑战性，这可能导致治疗过程中遇到的问题。其他疗法，如奥拉替尼、马罗皮坦、必需脂肪酸和口服 H1 受体阻断型抗组胺药，已被提出，但在 FASS 猫中的有效性证据有限。
Some standard treatments described above are thought to act through anti- inflammatory or immunomodulatory mechanisms. A possible explanation for the lack of response in some FASS cats may be the involvement of neurological mechanisms, such as cen tral sensitisation. This phenomenon has been described in chronic pruritus in humans and pain in osteoarthritic cats. Similar to pain sensitisation, chronic cutaneous neuroimmune interactions can heighten pruriceptive neuron responsiveness in the central nervous system (CNS), leading to alloknesis (itch from non- pruritic stimuli) and hyperknesis (exaggerated itch response). Although central sensitisation is recognised in atopic humans, it remains unstudied in cats with chronic pruritus. Gabapentin is a structural analogue of the gamma- aminobutyric acid (GABA) neurotransmitter, and a selective blocker of the α2δ subunit of voltage- gated calcium channels (participating in neuronal sensitisation). A common use of gabapentin in veterinary medicine, including for cats, is as a sedative. However, it has been shown to decrease chronic pruritus in humans as well as manifestations of central sensitisation in osteoarthritic cats with chronic osteoarthritis- related pain. Considering these facts, it is worth exploring whether gabapentin might be beneficial in cats with chronic pruritus. To the best of the authors' knowledge, no published studies have reported the use of gabapentin in cats with pruritus.
上述所描述的一些标准治疗方法被认为是通过抗炎或免疫调节机制起作用的。一些 FASS 猫缺乏反应的可能原因可能是涉及神经机制，例如中枢敏化。这种现象在人类的慢性瘙痒症和骨关节炎猫的疼痛中都有描述。与疼痛敏化类似，慢性皮肤神经免疫相互作用可以增强中枢神经系统（CNS）中的瘙痒神经元的反应性，导致异位性瘙痒（由非瘙痒刺激引起的瘙痒）和过度瘙痒（瘙痒反应过度）。虽然在特应性疾病人类中已认识到中枢敏化现象，但在患有慢性瘙痒症的猫中对其的研究仍处于起步阶段。加巴喷丁是一种γ-氨基丁酸（GABA）神经递质的结构类似物，是一种电压门控钙通道α2δ亚基的选择性阻滞剂（参与神经元敏化）。加巴喷丁在兽医用药中的一种常见用途是作为镇静剂，包括用于猫。然而，已有研究表明，它能够减轻人类的慢性瘙痒症状，同时还能缓解患有慢性骨关节炎相关疼痛的骨关节炎猫的中枢敏化症状。鉴于这些事实，值得探究加巴喷丁是否对患有慢性瘙痒的猫有益。据作者所知，目前尚未有关于加巴喷丁用于患有瘙痒症状的猫的已发表研究。
In order to evaluate the effectiveness of antipruritic treat ments in cats, various parameters, such as lesional score, can be assessed. One such tool is the Feline Dermatitis Extent and Severity Index (FeDESI), commonly used to assess clinical score in FASS. This clinical scale provides a specific score based on the severity of erythema, self- induced alopecia and excoriations in different regions of the body.
为了评估猫抗瘙痒疗法的效果，可以对多种参数进行评估，比如病变评分等。其中一种工具是猫皮炎范围与严重程度指数（FeDESI），它常用于评估 FASS 中的临床评分。这个临床量表根据机体不同部位的发红、自损性脱毛和抓痕的严重程度给出一个具体的评分。
Another complementary tool used to assess pruritus is actimetry, which involves accelerometer- based motor activity recording. Previous studies have shown that accelerometers are practical and safe and provide objective quantification of itch- associated movements in both children and adults suffering from atopic dermatitis (AD). In veterinary medicine, their use was documented to evaluate itch in atopic dogs. More recently, it has been used to evaluate activity profiles in osteoarthritic dogs and cats.
用于评估瘙痒的另一种辅助工具是放射测量学，它利用加速度计来记录运动活动。先前的研究表明，加速度计既实用又安全，并能客观地量化患有特应性皮炎（AD）的儿童和成人的瘙痒相关动作。在兽医领域，它们被用于评估特应性犬的瘙痒情况。最近，它还被用于评估骨关节炎犬和猫的活动模式。
The primary aim of this study was to assess the effect of prednis olone, ciclosporin and placebo, administered alone or in combi nation with gabapentin, on lesional score and motor activity in cats with FASS. The secondary aim was to describe the changes observed in actimetry as a complementary approach for pruritus assessment in this species.
本研究的主要目的是评估泼尼松龙、环孢素以及安慰剂（单独使用或与加巴喷丁联合使用）对患有 FASS 疾病的猫的皮肤病变评分和运动活动的影响。次要目的是描述通过活动计数法所观察到的变化，作为评估该物种瘙痒症状的辅助方法。
2 | Materials and Methods
2材料和方法
2.1 | Ethics
2.1伦理
All data were collected in compliance with the principles out lined in the Guide to the Care and Use of Experimental Animals published by the Canadian Council on Animal Care (CCAC) and the Guide for the Care and Use of Laboratory Animals pub lished by the US National Institutes of Health [28]. The study protocols were approved by the Institutional Animal Care and Use Committee of both Zoetis (no. A182W- CA- 22- 284) and the Faculty of Veterinary Medicine of the University of Montreal (no. 23- Rech- 2220). An ethical concern was a request to apply a controlled distribution of cats by exposing more severely af fected cats to the standard treatments and to put in the placebo group mostly cats with less severe lesions.
所有数据的收集均遵循了加拿大动物护理委员会（CCAC）发布的《实验动物护理与使用指南》以及美国国立卫生研究院发布的《实验室动物护理与使用指南》中所阐述的原则[28]。研究方案已获得佐特斯公司（编号：A182W- CA- 22- 284）和蒙特利尔大学兽医学院（编号：23- Rech- 2220）的机构动物护理与使用委员会的批准。伦理方面的一个关注点是提出了一种控制性分发猫的方案，即让病情更严重的猫接受标准治疗，并将病情较轻的猫主要安排在安慰剂组中。
2.2 | Animals
2.2动物
A total of 26 cats from a laboratory colony diagnosed with FASS were enrolled in this prospective, blinded, placebo- controlled study. The sample was a convenience sample, con strained by the size of the FASS cat colony, which limited the number of available subjects. Owing to the exploratory nature of the study, a power calculation was not performed. All animals were sterilised, with a majority being females (22 of 26). The mean age was 7.8 years (range 5–13 years). Most cats (23 of 26) were domestic short hair and long hair cats, with one of each of the following pure- bred cats: Devon rex, Birman and Abyssinian. Detailed inclusion and exclusion criteria, as well as the descrip tion of the five phases summarising the establishment of the colony, have already been published. All cats underwent a standard stepwise approach to rule out ectoparasites and skin infections, as well as an 8- week elimination diet trial. Both in tradermal (Stallergenes Greer) and serological (ALLERCEPT North American East panel; Heska diagnostic laboratory) test ing for environmental allergens were performed in all cats.
来自一个实验室猫群的 26 只被诊断患有 FASS 的猫被纳入了这项前瞻性、盲法、安慰剂对照研究。该样本为便利样本，受限于 FASS 猫群的规模，这限制了可用样本的数量。由于该研究具有探索性，因此未进行功效计算。所有动物均进行了绝育手术，其中大多数为雌性（22/26）。平均年龄为 7.8 岁（范围 5 - 13 岁）。大多数猫（23/26）是家养短毛猫和家养长毛猫，还有以下纯种猫各一只：德文卷毛猫、比尔曼猫和阿比西尼亚猫。详细的纳入和排除标准，以及总结该猫群建立过程的五个阶段的描述，已经发表过。所有猫都接受了标准的逐步方法来排除体外寄生虫和皮肤感染，并进行了为期 8 周的食物排查试验。在所有猫上都进行了环境过敏原的皮内测试（Stallergenes Greer）和血清学测试（ALLERCEPT 北美东部面板；Heska 诊断实验室）。
2.3 | Treatment Groups
2.3治疗组
Group assignments complied with ethical guidelines set by the International Animal Care and Use Committee (IACUC), with the most severely lesional cats allocated to either the prednis olone or ciclosporin groups. Cats were then assigned to three groups: prednisolone (Teva Canada Ltd) 1 mg/kg once daily per os (n = 9), ciclosporin (Atopica; Elanco) 7 mg/kg once daily p.o. (n = 8) and placebo (microcrystalline cellulose, Avicel; Chiron Compounding Pharmacy Inc.) 1 capsule once daily p.o. (n = 9). After a 12- week washout period, each treatment was adminis tered alone once daily for 5 weeks (Week [W]0 to W4), followed by combination with gabapentin (10 mg/kg once daily p.o. for 2 weeks, then 15 mg/kg twice daily p.o. for 1 week) for 3 weeks (W5–W7). In this study, the nomenclature W0 includes day (D)0 to D6, W1 includes D7 to D13 and so on.
实验组的分组遵循了国际动物护理和使用委员会（IACUC）制定的伦理准则，病情最严重的猫被分配到泼尼松龙组或环孢素组。随后，这些猫又被分为三个组：泼尼松龙1 毫克/千克，每日口服一次（n = 9），环孢素7 毫克/千克，每日口服一次（n = 8），以及安慰剂（微晶纤维素，Avicel）1 袋，每日口服一次（n = 9）。经过 12 周的洗脱期后，每种治疗单独进行，每日一次，持续 5 周（W 0至W4），随后与加巴喷丁（10 毫克/千克，每日口服一次，持续 2 周，然后 15 毫克/千克，每日口服两次，持续 1 周）联合使用 3 周（W5-W7）。在本研究中，“W0”包括D0 天至D6，W1包括D7 天至D13，以此类推。
2.4 | Assessment of Clinical (Lesional) Score (FeDESI)
2.4 |临床（病变）评分评估（FeDESI）
Clinical score was assessed using the FeDESI at multiple time points: W−8, W−4, W−1, W2, W4 and W7. Baseline (BSL) was established at W−1. The same two investigators conducted all assessments together and were blinded to key information, in cluding which cat belonged to which group and the correspond ing treatment received during the experiment. All cats were evaluated sequentially and consistently, with 42 body regions assessed for erythema, self- induced alopecia, and erosions/ex coriations. A severity score ranging from 0 to 5 was assigned for each type of lesion at each body region, yielding a maximal FeDESI score of 630.
临床评分通过 FeDESI 在多个时间点进行评估：W-8 周、W-4 、W-1、W2 、W4 和 W7 。基线（BSL）设定在 W-1 。同一两名研究人员共同进行所有评估，并且对关键信息（包括哪只猫属于哪个组以及实验期间所接受的相应治疗）保持保密。所有猫依次且一致地接受评估，对 42 个机体部位的发红、自损性脱毛和糜烂/抓痕进行评估。在每个机体部位上，针对每种类型的病变给予 0 到 5 的严重程度评分，从而得出最大 FeDESI 评分 630 分。
2.5 | Motor Activity Recordings
2.5 运动活动记录
Actimetry (locomotor activity monitoring) was assessed using a collar- attached accelerometer- based activity sensor (Actiwatch- Mini, Minimitter/Respironics, distributed by Bio- Lynx Scientific Equipment Inc.) set to local time and configured to record an epoch event (1 count/2 min). The amplitude of each count was later translated to a numeric value (from 0 to infinity) corresponding to the intensity of the actimetry count. Following an acclimatisation period before data collection, the device was maintained in place from W−9 to W8. To limit interference re lated to usual care and social activities by the laboratory team, 4 days of the week (Friday, Saturday, Sunday and Monday) were considered for the analysis and referred to as ‘weekends’ (WE) (total of 18 time points). Analyses focused on night- time actim etry (NAM) (between 17:00 and 06:59 h; 42 h per WE) to min imise the human–feline interactions. Inferential analysis was made by using a transformation of raw data in % of change, for each time point over time, versus BSL mean value (average of WE-9 to WE-1).
通过佩戴在颈圈上的基于加速度计的活动传感器（Actiwatch- Mini，由 Minimitter/Respironics 公司生产，由 Bio- Lynx 科学设备公司分销）来评估活动测量（运动活动监测）情况。该传感器设定为当地时间，并配置为记录一个事件周期（每 2 分钟记录 1 次计数）。每个计数的幅度随后被转换为一个数值（从 0 到无穷大），该数值对应于活动计数的强度。在数据收集前进行了一个适应期，然后从 W−9 到 W8 期间将设备保持在原位。为了减少实验室团队与常规护理和社交活动相关的干扰，将一周中的 4 天（星期五、星期六、星期天和星期一）用于分析，并将其称为“周末”（WE）（每个 WE 共有 18 个时间点）。分析重点是夜间活动测量（NAM）（17：00 至 06：59 之间；每个 WE 为 42 小时），以尽量减少人与猫的互动。通过将原始数据进行转换（以百分比变化形式）并与基线标准值（WE-9 至 WE-1 的平均值）进行比较，进行了推断性分析。
2.6 | Statistical Methods
2.6统计学方法
For inferential analyses related to the clinical score (FeDESI), a linear mixed model (LMM) was initially used. A log transforma tion of the dependent variable was applied to meet the residual normality assumption. Type III effects (effect of time, treatment and interaction between time × treatment) were calculated. Secondly, a repeated- measures generalised linear mixed (GLM) model was applied, using a zero- inflated negative binomial dis tribution to better discriminate a possible treatment effect with an α- value of 0.05. Incidence rate ratios were calculated by com paring the rate of the characteristic being studied in the group of interest (e.g., those receiving one treatment) to the rate in the comparison group (e.g., those receiving a different treatment).
对于与临床评分（FeDESI）相关的推断性分析，最初采用了线性混合模型（LMM）。对因变量进行了对数转换，以满足残差的正态性假设。计算了第三类效应（时间效应、治疗效应以及时间×治疗的交互效应）。其次，应用了重复测量广义线性混合（GLM）模型，使用零膨胀负二项分布来更好地区分可能的治疗效果，α值设为 0.05。通过将研究对象组（例如接受一种治疗的患者）中所研究特征的发生率与对照组（例如接受不同治疗的患者）的发生率进行比较，计算了发病率比值。
Normality of the NAM outcome was verified using the Shapiro Wilk test for all time points, and homogeneity of variances at BSL using the Levene test. Intra- and intergroup differences over time were analysed using a LMM for repeated measures employing the log- normal distribution. Treatment time points and their interactions were included as fixed effects. Data (in % change versus BSL mean) are represented as the estimated mean (least square mean [LSM]) with a 95% confidence interval (CI). When justified, Bonferroni correction for multiple comparisons was applied. To assess the relationship between FeDESI and NAM at baseline, a Spearman correlation test was performed, producing a Spearman correlation coefficient (rho). A boot strapping method (random resampling with 10,000 repetitions) was used to generate a 95% CI around the Pearson correlation coefficient.
使用夏皮罗-威克检验对所有时间点的 NAM 结果进行了正态性验证，并使用莱文检验对基线时的方差齐性进行了验证。通过重复测量的线性混合模型（采用对数正态分布）分析了不同组间和组内随时间的变化差异。将治疗时间点及其相互作用作为固定效应纳入模型。数据（相对于基线平均值的百分比变化）以估计均值（最小二乘均值[LSM]）的形式呈现，并附有 95%置信区间（CI）。在有合理依据的情况下，对多重比较应用了博尔菲尼奥校正。为了评估 FeDESI 与 NAM 在基线时的关系，进行了斯皮尔曼相关性检验，得出斯皮尔曼相关系数（rho）。使用随机抽样方法（10，000 次重复）生成了皮尔逊相关系数的 95%置信区间。
3 | Results
3结果
3.1 | Clinical Score (FeDESI)
3.1临床评分（FeDESI）
The study population exhibited overall mild- to- moderate dis ease severity. The results of the descriptive analyses, including all individuals, are shown in Figure 1. The median FeDESI score at baseline was 12.0 (mean 17.1, range 0–46) for the predniso lone group, 8.5 (mean 13.3, range 0–32) for the ciclosporin group and 2.0 (mean 3.7, range 0–12) for the placebo group. Post hoc analysis revealed no significant differences between groups at baseline (p = 0.710). Median scores [range] for each group for every time point are shown in Table 1. With the LMM, there were significant effects of time (p < 0.001) and a time × treat ment interaction (p = 0.021), yet no significant intercept effect of treatment (p = 0.710) and no difference at BSL (W−1) among the three groups.
研究对象的整体病情严重程度为轻至中度。描述性分析的结果（包括所有个体）如图 1 所示。基线时，泼尼松组的 FeDESI 中位数评分是 12.0（平均值 17.1，范围 0 - 46），环孢素组为 8.5（平均值 13.3，范围 0 - 32），安慰剂组为 2.0（平均值 3.7，范围 0 - 12）。事后分析显示，各组在基线时无显著差异（p = 0.710）。每个时间点各组的中位分数[范围]如表 1 所示。使用线性混合模型（LMM），时间（p < 0.001）和时间×治疗交互作用（p = 0.021）有显著影响，但治疗的截距效应无显著差异（p = 0.710），且三组在基线（W−1）时无差异。
Intragroup comparisons (within- time) also were tested. In the prednisolone group, a significant decrease in FeDESI scores was noted between W−1 and W4 (p = 0.008), W−1 and W7 (p < 0.001), W2 and W7 (p = 0.003) and between W4 and W7 (p = 0.026). In the ciclosporin group, a significant FeDESI scores decrease was noted between W−1 and W7 (p = 0.002), W2 and W7 (p = 0.017) and between W4 and W7 (p = 0.034). By contrast, the placebo group showed no statistically significant variation in FeDESI score.
还进行了组内比较（时间维度内）的测试。在泼尼松龙组中，从 W−1 到 W4（p = 0.008）、W−1 到 W7（p < 0.001）、W2 到 W7（p = 0.003）以及 W4 到 W7（p = 0.026）之间，FeDESI 评分均显著下降。在环孢素组中，从 W−1 到 W7（p = 0.002）、W2 到 W7（p = 0.017）以及 W4 到 W7（p = 0.034）之间，FeDESI 评分也显著下降。相比之下，安慰剂组的 FeDESI 评分没有显示出统计学上的显著变化。
Throughout the study, the FeDESI score remained 0 for three individuals—one per treatment group. These cats were excluded from inferential analyses to better reflect the effect of treat ment in responders, as treatment effect cannot be appreciated in persistently alesional cats. Therefore, subsequent inferential analyses were performed on 23 of 26 cats using a GLM model with a zero- inflated negative binomial distribution. The mean percentage of change in FeDESI score reported to BSL for each group over time is illustrated in Figure 2. From W−1 (BSL) to W4, FeDESI scores decreased by 45.6% and 24.1% in the prednis olone and ciclosporin groups, respectively and increased by 4.4% in the placebo group.
在整个研究过程中，有三只猫的 FeDESI 评分始终为 0——分别来自两个治疗组中的各一只。为了更准确地反映治疗对反应者的影响，这些猫被排除在推断性分析之外，因为持续性皮肤病变的猫无法体现治疗效果。因此，后续的推断性分析是在 26 只猫中的 23 只上进行的，使用具有零膨胀负二项分布的 GLM 模型。各组 FeDESI 评分随时间的变化的平均百分比变化情况如图 2 所示。从 W−1（BSL）到 W4，泼尼松组和环孢素组的 FeDESI 评分分别下降了 45.6%和 24.1%，而安慰剂组则增加了 4.4%。
When compared to placebo, both the prednisolone and ciclosporin groups showed significantly greater reductions in FeDESI scores (p < 0.001). After the addition of gabapen tin from W5 onwards, the FeDESI scores steeply decreased in all three groups, presenting a similar downward slope in all three groups. Gabapentin significantly improved FeDESI scores in all groups (p < 0.001). From W4 to W7, after the addi tion of gabapentin, FeDESI scores further decreased by 37.4%, 48.8% and 43.2% in the prednisolone, ciclosporin and placebo groups, respectively. Overall, compared to BSL, FeDESI scores decreased by 83.0%, 72.9% and 31.1% in the prednisolone, ciclosporin and placebo groups complemented with gabapentin, respectively, at W7. The calculated incidence rate ratio (IRR) to significantly decrease FeDESI score versus placebo for gabapentin, prednisolone and ciclosporin was 2.59, 1.90 and 1.31 (p < 0.001), respectively. All IRR coefficients were significantly different from 0 (p < 0.0001) (see Table S1). However, only prednisolone and gabapentin significantly improved the incidence rate of FeDESI scores compared to placebo, as in dicated by their IRRs having 95% CIs with lower bounds > 1. By contrast, ciclosporin did not significantly improve the inci dence rate of FeDESI scores compared to placebo, because the lower bound of its 95% CI was < 1. Additionally, prednisolone did not significantly improve the incidence rate of FeDESI scores compared to ciclosporin, as the 95% CI of its IRR in cluded 1. When receiving gabapentin, cats had 2.59- fold more chances to decrease their FeDESI score than if they received only a placebo.
与安慰剂组相比，泼尼松龙组和环孢素组的 FeDESI 评分均显著降低（p < 0.001）。从 W5 开始添加加巴喷丁后，所有三组的 FeDESI 评分均大幅下降，且三组的下降趋势相似。加巴喷丁显著改善了所有组的 FeDESI 评分（p < 0.001）。从 W4 到 W7，在添加加巴喷丁后，泼尼松龙组、环孢素组和安慰剂组的 FeDESI 评分分别进一步下降了 37.4%、48.8%和 43.2%。总体而言，在 W7 时，与基础状态（BSL）相比，泼尼松龙组、环孢素组和安慰剂组加上加巴喷丁后，FeDESI 评分分别降低了 83.0%、72.9%和 31.1%。加巴喷丁、泼尼松龙和环孢素显著降低 FeDESI 评分与安慰剂相比的计算发生率比值（IRR）分别为 2.59、1.90 和 1.31（p < 0.001），所有 IRR 系数均与 0 显著不同（p < 0.0001）（见表 S1）。然而，只有泼尼松龙和加巴喷丁显著提高了 FeDESI 评分的发生率，这与它们的 IRR（干预组与对照组的相对风险）具有 95% 置信区间（下限大于 1）的情况相符。相比之下，环孢素并未显著提高 FeDESI 评分的发生率，因为其 95% 置信区间的下限小于 1。此外，泼尼松龙也没有显著提高 FeDESI 评分的发生率，与环孢素相比，其 IRR 的 95% 置信区间包含 1。当使用加巴喷丁时，猫咪降低 FeDESI 评分的几率是仅使用安慰剂的 2.59 倍。
3.2 | Motor Activity Recording (Actimetry)
3.2 |运动活动记录（放射测量学）
Evolution of NAM over each WE revealed significant effects for treatment and time (p < 0.0001), as well as the time × treat ment interaction (p = 0.005). A graphical representation of the percentage of change in NAM compared to BSL at each time point is illustrated in Figure 3. At baseline, there was no significant correlation between NAM and FeDESI scores (Spearman = 2335.40; n = 27; p = 0.323); the rho between the two variables was 0.20 [−0.22; 0.57], indicating a weak correlation.
在每个WE内对 NAM 的演变分析显示，治疗和时间因素具有显著影响（p < 0.0001），同时时间×治疗的交互作用也具有显著意义（p = 0.005）。图 3 展示了每个时间点与基线状态相比 NAM 的变化百分比与 FeDESI 评分之间的关系图。在基线时，NAM 与 FeDESI 评分之间没有显著相关性（斯皮尔曼相关系数 = 2335.40；n = 27；p = 0.323）；这两个变量之间的相关系数为 0.20 [−0.22； 0.57]，表明相关性较弱。
For the intergroup NAM pairwise comparison, a signifi cant difference in actimetry data (LSM ± 95% CI) was noted among the three groups as soon as after the first week of ad ministration, WE0 (p < 0.028), with a decreased motor activ ity for treated FASS cats and particularly in the prednisolone group. The motor activity in the prednisolone group remained lower at WE1 (−42.84% ± 16.99%) compared to the ciclospo rin (−9.68% ± 18.02%) and placebo (8.19% ± 16.99%) groups (p < 0.009). All time points were significantly different from BSL (p < 0.001) for the prednisolone group, with a stabilised decrease from WE0 to WE4 (approximatley 50%). Over the same period, NAM in the placebo group did not evolve significantly, while a delayed NAM decrease (starting at WE2) was noted in the cic losporin group, lower (approximately 27.5%) at WE2 and WE3. The introduction of gabapentin led to a further decrease in motor activity for the prednisolone (WE5 −55.66% ± 16.99%; WE6 −67.64% ± 16.99%) and ciclosporin (WE5 −33.54% ± 18.02%; WE6 −33.83% ± 18.02%; p < 0.041) groups. There was no more intergroup difference between the ciclosporin and the placebo groups (p > 0.053) as gabapentin induced a significant decrease in NAM of the placebo group from WE5 to WE7, compared to WE4 (approximately 32.5%; p < 0.008). A nonsignificant increase in motor activity was observed between W6 and W7 in the pred nisolone (p = 0.062), the ciclosporin (p = 0.190) and the placebo (p = 0.340) groups. Stopping gabapentin was reflected, at WE8, by an increase in motor activity for all three groups (WE8 pred nisolone −45.80% ± 31.36%; ciclosporin −25.68% ± 26.82%; pla cebo 20.29% ± 21.37%), more importantly for the placebo group (p < 0.009).
对于组间 NAM 的两两比较，从给药第一周开始，三个组的活动测定数据（LSM ± 95%置信区间）就显示出显著差异，即 WE0 时（p < 0.028），接受治疗的 FASS 猫的运动活动减少，尤其是泼尼松龙组。在 WE1 时，泼尼松龙组的运动活动仍低于环孢素组（-42.84% ± 16.99%）和安慰剂组（8.19% ± 16.99%）（p < 0.009）。对于泼尼松龙组，所有时间点与基线值（BSL）相比均显著不同（p < 0.001），从 WE0 到 WE4 逐渐减少（大约 50%）。在同一时期，安慰剂组的 NAM 没有显著变化，而环孢素组则出现了延迟的 NAM 减少（从 WE2 开始），在 WE2 和 WE3 时更低（约 27.5%）。加巴喷丁的引入导致泼尼松龙组（WE5 -55.66% ± 16.99%；WE6 -67.64% ± 16.99%）和环孢素组（WE5 -33.54% ± 18.02%；WE6 -33.83% ± 18.02%）的运动活动进一步减少（p < 0.041）。环孢素组与安慰剂组之间的组间差异不再存在（p > 0.053）。而加巴喷丁使安慰剂组从 WE5 到 WE7 的神经活动幅度（NAM）显著降低，相较于 WE4（约 32.5%；p < 0.008）。在泼尼松龙组（p = 0.062）、环孢素组（p = 0.190）和安慰剂组（p = 0.340）中，W6 到 W7 期间的运动活动未观察到显著增加。在 WE8 时停止加巴喷丁治疗后，所有三组的运动活动均有所增加（泼尼松龙组 -45.80% ± 31.36%；环孢素组 -25.68% ± 26.82%；安慰剂组 20.29% ± 21.37%），其中安慰剂组更为显著（p < 0.009）。
4 | Discussion
4讨论
This study showed a significant improvement in clinical score in FASS cats treated with prednisolone and ciclosporin, which was faster and more intense with prednisolone, along with a corre sponding decrease in motor activity. A supplemental effect was observed when gabapentin was added to all treatment regimens, further decreasing both clinical scores and motor activity.
这项研究表明，使用泼尼松龙和环孢素治疗的 FASS 猫在临床评分方面有显著改善，其中使用泼尼松龙的效果更快、更显著，同时运动活跃度也有所降低。当在所有治疗方案中添加加巴喷丁时，还观察到了一种辅助效果，进一步降低了临床评分和运动活跃度。
Although not formally validated, the FeDESI used in this study has been described as a more practical and granular scale. Based on the results of this study, as expected, both predniso lone and ciclosporin significantly improved FeDESI scores,consistent with their common use in treating FASS. A significant decrease in FeDESI scores was noted in the prednisolone group from W−1 to W4, unlike in the ciclosporin group, sug gesting a faster onset of action. This is in agreement with studies reporting a delayed onset of ciclosporin's full therapeutic effect, typically at around 4 weeks. Moreover, advanced statisti cal modelling confirmed that the prednisolone group exhib ited a more rapid and pronounced reduction in FeDESI scores compared to the ciclosporin group. Following the addition of gabapentin, all treatment groups showed further score reductions with a similar downward slope, while the placebo group showed no such improvement before its addition. Interestingly, the highest IRR was observed for gabapentin (2.59), indicating that cats treated with gabapentin were 2.59- fold more likely to reduce their FeDESI scores than those on placebo. This may be attributed to a reduction in central sensitisation, which in turn led to fewer pruritus- induced lesions, such as self- inflicted alo pecia or excoriations.
尽管该研究中所使用的 FeDESI 方法尚未经过正式验证，但据描述，它具有更实用且更精细的测量尺度。根据本研究的结果，正如预期的那样，泼尼松龙和环孢素均显著提高了 FeDESI 评分，这与它们在治疗 FASS 中的常规应用相一致。从W-1 周到W4，泼尼松龙组的 FeDESI 评分显著下降，而环孢素组则没有出现这种情况，这表明其作用的显现速度更快。这与一些研究报告的环孢素完全治疗效果的延迟显现（通常在约 4 周时）相一致。此外，先进的统计模型证实，泼尼松龙组在 FeDESI 评分方面的下降速度比环孢素组更快、更显著。在添加加巴喷丁后，所有治疗组的评分均进一步下降，且下降趋势相似，而安慰剂组在添加加巴喷丁之前没有出现这种改善。有趣的是，加巴喷丁的累积反应率最高（2.59），这表明接受加巴喷丁治疗的猫比接受安慰剂的猫减少 FeDESI 评分的可能性高出 2.59 倍。这可能是由于中枢敏化作用的减弱所致，而这种减弱又导致了较少由瘙痒引起的病变，比如自损性脱毛或抓痕。
A statistical model was used to exclude cats with a persistently zero FeDESI score throughout the study to better isolate the treatment effect in cats with varying FeDESI scores. However, the inclusion of these cats was still justified owing to the diverse clinical presentation of pruritus in FASS, where significant pru ritus can occur despite minimal lesions. This is particularly rel evant given that one of the study's objectives was to assess motor activity (actimetry) even in cats presenting with mild clinical signs or low FeDESI scores, as this may highlight the value of this tool in detecting pruritus- associated behaviours in the ab sence of visible skin lesions. Previous studies have reported that accelerometers are use ful for assessing night- time itch both in children and adults suffering from AD. Likewise, this modality of evalu ation has been used in dogs to assess pruritus. In cats, actimetry has been used to record motor activity under various feeding and housing conditions, in response to weight management strategies, and in the context of pain assessment and its management in osteoarthritic cats.
采用了一种统计模型，将在整个研究过程中 FeDESI 评分始终为零的猫排除在外，以更好地分离出不同 FeDESI 评分的猫的治疗效果。然而，将这些猫纳入研究仍然是合理的，因为 FASS 中的瘙痒症状表现形式多种多样，即使有轻微的病变也可能出现严重的瘙痒。这一点尤为重要，因为该研究的一个目标是评估即使在表现出轻微临床症状或 FeDESI 评分较低的猫中，运动活动（活动计数法）的情况，因为这可能凸显出该工具在没有可见皮肤病变的情况下检测瘙痒相关行为的价值。先前的研究报告称，加速度计可用于评估儿童和成人特应性皮炎患者夜间瘙痒的情况。同样，这种评估方式也用于评估犬的瘙痒情况。在猫中，活动计数法被用于记录在各种喂食和居住条件下、对体重管理策略的反应以及在骨关节炎猫的疼痛评估及其管理中的运动活动。
In this study, actimetry was used as an adjunctive tool to monitor itch- related behaviours in studied cats, based on the premise that the intensity of motor activity may correlate with the severity of pruritus- associated behaviours such as scratching, licking, nibbling and rubbing. FASS cats treated with prednisolone or ciclosporin exhibited a significant de crease in motor activity (by approximatively 50% and 27.5%, respectively), in NAM data compared to BSL. The decreased intensity in NAM was associated with the improvement rate and intensity in FeDESI, being more important for predniso lone than for ciclosporin. Although only a weak correlation was suggested, a tendency was still observed. Furthermore, the decrease in motor activity after the addition of gabapen tin in all three groups may suggest a supplementary beneficial effect on pruritus, which may have reduced the occurrence of itch- related behaviours. Compared to the last time point (WE4) before introducing the gabapentin, the NAM down ward slope observed in the placebo group (Figure 3) suggests an effect on central sensitisation rather than a decrease that might be attributed solely to the passage of time. Interestingly,it was associated with a concomitant benefit in cutaneous le sions, where the downward slope in FeDESI score was similar in all three groups receiving the same gabapentin treatment (see Figure 2). Moreover, the loss of a significant difference in motor activity between the ciclosporin and the placebo groups at WE5, WE6 and WE7, and its reoccurrence at WE8 (after stopping gabapentin), supports the notion that gabapentin contributed to a similar reduction of pruritus in both groups.
在本研究中，采用动作计数法作为辅助手段来监测研究对象猫的瘙痒相关行为，其依据是运动活动的强度可能与瘙痒相关行为（如抓挠、舔舐、咀嚼和摩擦）的严重程度相关。接受泼尼松龙或环孢素治疗的 FASS 猫与基础正常状态（BSL）相比，其运动活动显著减少（分别减少了约 50%和 27.5%）。在 NAM 数据中，运动活动的减少与 FeDESI 的改善率和强度相关，而对泼尼松龙的这种影响比对环孢素的影响更为显著。尽管仅显示出较弱的相关性，但仍观察到了一种趋势。此外，在所有三组中添加加巴喷丁后运动活动的减少可能表明对瘙痒有补充的有益作用，这可能减少了瘙痒相关行为的发生。与引入加巴喷丁之前的时间点（WE4）相比，安慰剂组观察到的 NAM 下降斜率（图 3）表明其作用是针对中枢敏化，而非仅仅由于时间的推移而产生的减少。有趣的是，它还带来了皮肤病变方面的同步改善，即在所有接受相同加巴喷丁治疗的三组中，FeDESI 评分的下降趋势是相似的（见图 2）。此外，在 WE5、WE6 和 WE7 时，环孢素组和安慰剂组在运动活动方面的显著差异消失，并且在停止加巴喷丁治疗后的 WE8 时又重新出现这种差异（这支持了加巴喷丁在两组中均对瘙痒症状的减轻起到了类似作用的观点）。
Another possible explanation for this trend could be the sedative effects of gabapentin. However, a previous study in osteoarthritic cats using a similar dose reported increased night- time activity and reduced central sensitisation, which was likely to be at tributed to analgesic effects rather than sedation. Moreover, a recent study evaluating the effectiveness of trazodone and gabapentin and their combination, for oral sedation in healthy cats showed that a single 10 mg/kg oral dose of gabapentin failed to provide significant sedation in any of the 21 cats included in the study. Van Haaften et al. also examined a single preap pointment dose of gabapentin (100 mg per cat; 13.0–29.4 mg/kg) and demonstrated its efficacy in reducing stress and aggression. Only two of 20 cats showed marked sedation after returning home (doses of 25.6 and 29.4 mg/kg, respectively). While the dosage used in the present study was much lower (10–15 mg/ kg), a sedative effect remains possible. Anecdotally, no signs of ataxia, behavioural changes or altered mentation were observed in this study. Lastly, a nonsignificant increase in motor activity at W7, following a dose increase, further suggests that sedation was unlikely to cause reduced activity. This increase may reflect other factors, such as osteoarthritis, rather than pruritus.
这种趋势的另一种可能解释可能是加巴喷丁的镇静作用。然而，此前一项针对骨关节炎猫的研究（使用相同剂量）报告称，夜间活动增加且中枢敏化现象减轻，这很可能归因于镇痛作用而非镇静作用。此外，最近一项评估曲唑酮和加巴喷丁及其组合在健康猫中口服镇静效果的研究表明，单次 10 毫克/千克的加巴喷丁口服剂量在纳入研究的 21 只猫中均未能提供显著的镇静效果。Van Haaften等人还研究了单次术前剂量的加巴喷丁（每只猫 100 毫克；13.0 - 29.4 毫克/千克），并证明其在减轻压力和攻击行为方面的有效性。在回家后的 20 只猫中，只有 2 只表现出明显的镇静（分别为 25.6 和 29.4 毫克/千克）。尽管本研究中使用的剂量要低得多（10 - 15 毫克/千克），但仍有镇静作用的可能性。据传闻，在这项研究中未观察到共济失调、行为变化或意识改变的症状。最后，在剂量增加后第 7 周时，运动活动量并未出现显著增加，这进一步表明镇静作用不太可能导致活动量减少。这种增加可能反映了其他因素，如骨关节炎，而非瘙痒。
In order to minimise confounding factors, this study focused on NAM data. This choice was based on the prevalence of night-time pruritus, as supported by several studies. One reported higher night-time activity in atopic dogs compared to healthy ones. Another showed a correlation between ac celerometer data and observed pruritus in kennelled dogs. Additionally, night-time data (24.00–6.00h) also showed better repeatability when comparing untreated and prednisolone- treated dogs. Given the laboratory context of the current study, it was hypothesised that cats would exhibit less interfer ence with their natural behaviours during the night when feeding, medication administration, playing and cleaning routines were suspended. Although WE time points were analysed, future studies may benefit from using broader timeframes to better assess daily variation in activity and pruritus. This could provide a more comprehensive understanding of treatment effects.
为了尽量减少干扰因素，本研究重点关注了 NAM 数据。这一选择是基于夜间瘙痒症的普遍发生情况，这一点得到了多项研究的支持。一项研究显示，过敏症犬在夜间活动量高于健康犬。另一项研究则表明，加速度计数据与寄养犬观察到的瘙痒之间存在关联。此外，夜间数据（24:00 - 6:00）在未治疗犬和泼尼松龙治疗犬的比较中也显示出更好的重复性。鉴于当前研究的实验室背景，假设猫在夜间进食、用药、玩耍和清洁等常规活动暂停时，其自然行为受到的干扰会更小。尽管分析了 WE 时间点，但未来的研究或许可以从更宽的时间框架中受益，以便更好地评估日常活动和瘙痒的差异。这可能会提供更全面的治疗效果理解。
In humans, actimetry has been shown to have a good sensitivity, yet its specificity is limited. To improve the positive predictive value, additional tools are needed. Although not well- described in cats, the integration of artificial intelligence with video data may help differentiate normal activity from itch- related behaviours. Future studies may explore these avenues to enhance itch detection and support the ongoing need for effective adjunctive tools in pruritus research.
在人类中，动作计数法已被证明具有良好的敏感性，但其特异性却有限。为了提高阳性预测值，还需要其他辅助手段。虽然在猫上这方面尚未有详细描述，但将人工智能与视频数据相结合或许有助于区分正常活动与与瘙痒相关的行为。未来的研究或许会探索这些途径，以提高瘙痒检测的准确性，并满足瘙痒研究中对有效辅助工具的持续需求。
Emerging evidence supports the role of central sensitisation in chronic itch. While pruritus can be transmitted through specific neuronal pathways (e.g., pruritus- specific histamine- dependent mechanically insensitive C- fibres), numerous neurotransmitters (e.g., substance P, glutamate, opioids) are in volved in both pain and itch. Central sensitisation, a well- studied phenomenon in algology, involves heightened CNS responses after prolonged stimulation, persisting even after the initial trigger has resolved. The same process has been described in humans suffering from chronic itch. A parallel can be drawn with itch, as previous studies highlight overlapping neurological pathways, with both conditions sharing features such as generalised sensations and sensitisation- associated signs and similar treatment approaches.
新的研究证据表明，中枢敏化在慢性瘙痒中起着重要作用。虽然瘙痒可以通过特定的神经元通路（例如，与瘙痒相关的特异性组胺依赖性机械不敏感 C 神经纤维）进行传递，但许多神经递质（例如，P 物质、谷氨酸、阿片类物质）都参与了疼痛和瘙痒的产生过程。在痛觉学领域中，中枢敏化这一现象已被深入研究，它指的是在长时间刺激后中枢神经系统反应增强的现象，即使最初的触发因素已经消失，这种反应仍会持续存在。在患有慢性瘙痒的人类患者中也发现了同样的过程。与瘙痒类似，先前的研究表明存在重叠的神经通路，两种情况都具有共同的特征，如普遍的感觉和与敏化相关的症状，以及类似的治疗方法。
Central sensitisation has been demonstrated in cats with os teoarthritis. A preliminary study (unpublished data) compared mechanical temporal summation tolerance in 33 FASS, 10 osteoarthritic and 24 healthy cats. Results showed similar tolerance in FASS and osteoarthritic cats, yet differed from healthy cats, suggesting similar spinal sensitisation and/ or neural pathways for pain and itch. A related study (published abstract) further supported central sensitisation in FASS cats, demonstrating a response to gabapentin, enhanced by ciclosporin.
在患有骨关节炎的猫上已证实存在中枢敏化现象。一项初步研究（未发表数据）对 33 只 FASS 猫、10 只骨关节炎猫和 24 只健康猫的机械时间总和耐受能力进行了比较。结果显示，FASS 猫和骨关节炎猫的耐受能力相似，但与健康猫不同，这表明它们的脊髓存在类似的敏化现象以及/或者疼痛和瘙痒的神经通路相似。另一项相关研究（已发表摘要）进一步证实了 FASS 猫存在中枢敏化现象，表明它们对加巴喷丁有反应，并且这种反应在环孢素的辅助下会增强。
Gabapentin, an effective treatment for neuropathic pain in hu mans and animals, has shown promise in managing chronic itch unresponsive to conventional therapy in people as a conse quence of its modulatory effects on the CNS. Its action on central sensitisation is well documented, reducing allodynia and hyperalgesia by decreasing NMDA receptor activation, thereby inhibiting excitatory neurotransmitter release, such as glutamate. The latter plays a key role in excitatory signal ling in the CNS and in the maintenance of central sensitisation. Considering the potential role of gabapentin in central sensitisation, it may help explain the effectiveness in re ducing pruritus in FASS.
加巴喷丁是一种对人类和动物神经性疼痛有显著疗效的药物，其在治疗对常规疗法无反应的慢性瘙痒方面也展现出了良好的效果，这是因为其对中枢神经系统的调节作用。其对中枢敏化的作用已被充分证实，通过减少 NMDA 受体的激活来减轻异常感觉和过度疼痛反应，从而抑制兴奋性神经递质的释放，如谷氨酸。谷氨酸在中枢神经系统的兴奋信号传导以及中枢敏化的维持中起着关键作用。鉴于加巴喷丁在中枢敏化方面可能发挥的作用，它或许有助于解释其在减轻 FASS 引起的瘙痒方面的有效性。
Although a somatosensory profile for cats has not yet been pub lished, the findings of our study suggest that central sensitisation may be involved in FASS. Assessing their somatosensory profile through quantitative sensory tests such as response to mechanical temporal summation or punctate tactile paw withdrawal threshold, would be beneficial for further inves tigating the role of central sensitisation in this context.
虽然关于猫的躯体感觉特征尚未有相关研究成果发表，但我们的研究结果表明，中枢敏感能力可能与FASS有关。通过诸如对机械时间叠加的反应或点状触觉爪部撤回阈值等定量感觉测试来评估它们的躯体感觉特征，将有助于进一步探究中枢敏感能力在这一情况下的作用。
This study has limitations, including the small sample size and social context of the cat colony. The laboratory setting may have altered normal cat behaviour, preventing full expression of itch behaviours. Additionally, no healthy control cats were included, which could have helped establish a baseline for motor activity in non- FASS cats. Another limitation is the potential sedative ef fect of gabapentin, which may have influenced actimetry results and FeDESI scores. Finally, the inability to distinguish pruritus- related from normal motor activity without video validation re mains a limitation.
本研究存在一些局限性，包括样本量较小以及猫群所处的社会环境因素。实验室环境可能会改变猫的正常行为，从而阻碍了瘙痒行为的完全表现。此外，未纳入健康的对照猫，这可能会有助于为非 FASS 猫的运动活动建立一个基准。另一个局限性是加巴喷丁可能产生的镇静作用，这可能影响了活动计数结果和 FeDESI 评分。最后，由于无法在没有视频验证的情况下区分与瘙痒相关的正常运动活动和非相关活动，这一问题仍然是一个局限性。
5 | Conclusions
5结论
To the best of the authors' knowledge, this is the first study eval uating gabapentin's effect on clinical scores and device- recorded motor activity in FASS cats. The results of this study suggest that gabapentin may enhance the beneficial effects of prednisolone and ciclosporin in alleviating pruritus, possibly by mitigating the contribution of central sensitisation in perpetuating clinical signs. Further studies are required to better define the somato sensorial profile in pruritic cats and to clarify the beneficial role of gabapentin in cats with FASS.
据作者们所知，这是首次对 FASS 猫进行的研究，旨在评估加巴喷丁对临床评分和设备记录的运动活动的影响。本研究的结果表明，加巴喷丁可能增强泼尼松龙和环孢素在缓解瘙痒方面的有益效果，这可能是通过减轻中枢敏化的作用来缓解临床症状的持续发展。还需要进一步的研究来更明确瘙痒性猫的躯体感觉特征，并阐明加巴喷丁在患有 FASS 的猫中的有益作用。
FIGURE 1 | Clinical score (FeDESI) evaluation for each treatment group over time. FeDESI, Feline Dermatitis Extent and Severity Index; W, week. Bold line, median; outliers, ×; box, 1st–3rd quartile; bars, 10th and 90th percentile. a,b,cWithin- time difference. When considering two time points, different letters indicate a significant difference (p < 0.05; see text for exact p- values).
图 1 | 各治疗组临床评分（FeDESI）随时间的变化情况。FeDESI，猫皮炎范围与严重程度指数；W，周。粗线表示中位数；异常值用×表示；方框表示第一至第三四分位数；条形表示第 10 百分位数和第 90 百分位数。a、b、c 同一时间内的差异。当考虑两个时间点时，不同的字母表示存在显著差异（p < 0.05；见文内详细 p 值）。
TABLE 1 | Median Feline Dermatitis Extent and Severity Index (FeDESI) score [range] for each treatment group at each time point.
表 1 | 各治疗组在每个时间点的猫皮炎程度与严重程度指数（FeDESI）得分[范围]。
FIGURE 2 | Mean percentage of change from baseline in FeDESI score by group over time. FeDESI, Feline Dermatitis Extent and Severity Index; BSL, baseline; W, week. FeDESI scores decreased significantly from W−1 to W4 in both the prednisolone (by 45.6%) and ciclosporin (by 24.1%) groups, compared to a 4.4% increase in the placebo group. Overall, by W7, FeDESI scores were reduced by 83.0%, 72.9% and 31.1% in the prednisolone- gabapentin, ciclosporin- gabapentin and placebo- gabapentin groups, respectively.
图 2 | 各组随时间推移的 FeDESI 评分基线变化的平均百分比。FeDESI，猫皮炎范围与严重程度指数；BSL，基线；W，周。与安慰剂组相比，泼尼松龙组（下降 45.6%）和环孢素组（下降 24.1%）的 FeDESI 评分从 W−1 到 W4 显著降低，而安慰剂组则有 4.4%的上升。总体而言，到 W7 时，泼尼松龙-加巴喷丁组、环孢素-加巴喷丁组和安慰剂-加巴喷丁组的 FeDESI 评分分别降低了 83.0%、72.9%和 31.1%。
FIGURE 3 | Night- time actimetry monitoring (estimated mean of model) for each group over time, expressed as percentage of change versus BSL (baseline). NAM, night- time actimetry monitoring; WE, weekend. a,b,cIntergroup significant difference: Different letters indicate a significant dif ference (p < 0.05; see text for exact p- values)
图 3 | 各组夜间活动监测数据（模型估算平均值）随时间的变化情况，以相对于基线（初始状态）的百分比形式呈现。NAM，夜间活动监测；WE，周末。a、b、c 各组间存在显著差异：不同的字母表示存在显著差异（p < 0.05；请参阅文后获取确切的 p 值） | 
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发表于 2025-7-19 18:51:49
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