Background

Postoperative pain is a common clinical problem that, in preclinical studies, has almost exclusively been studied in males. Altered C-fibre activity-dependent slowing (ADS) is a potential underlying mechanism, given it is altered after tissue inflammation and nerve injury, but this has not been explored post-incision. We therefore investigated the effect of hind-paw incision on C-fibre ADS in both sexes and the involvement of voltage-gated sodium channels (Na_V) as they contribute to ADS. We also assessed mechanical and thermal sensitivity post-incision in both sexes.

Methods

Dorsal roots were isolated from hind-paw incision (2–4 days post-surgery) or naive (control) juvenile rats of both sexes. Compound action potential recordings were made to assess C-fibre ADS in response to ×40 stimuli at 2 and 10 Hz and repeated in the presence of 20 nM tetrodotoxin/vehicle. Data were quantified by the normalised change in latency (negative peak) and width (positive-to-positive peak) of the triphasic C-fibre response. Hind-paw mechanical withdrawal thresholds and thermal withdrawal latencies were measured pre- and post-incision.

Results

Incision facilitates C-fibre ADS in both sexes, with more pronounced facilitation in females. Tetrodotoxin induces sex- and injury-dependent changes in C-fibre ADS that were distinct between latency and width measures. Hind-paw incision induced comparable mechanical hypersensitivity in both sexes but less peak heat hypersensitivity in females.

Conclusions

Hind-paw incision induces sex-dependent changes in C-fibre activity-dependent slowing, which likely contribute to the observed sex difference in peak thermal hypersensitivity. This may reflect sex- and incision-induced differences in functional expression of Na_V channels that differs by C-fibre subtype.

中文翻译：

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术后疼痛促进大鼠 C 纤维活性依赖性减慢并以性别依赖性方式诱导热超敏反应

背景

术后疼痛是一个常见的临床问题，在临床前研究中，几乎只在男性中进行了研究。改变的 C 纤维活动依赖性减慢 (ADS) 是一种潜在的潜在机制，因为它在组织炎症和神经损伤后发生了改变，但这尚未在切口后进行探索。因此，我们研究了后爪切口对两性 C 纤维 ADS 的影响以及电压门控钠通道 (Na _V ) 的参与，因为它们有助于 ADS。我们还评估了两性切口后的机械和热敏感性。

方法

从后爪切口（手术后 2-4 天）或幼年（对照）两性幼鼠中分离背根。进行复合动作电位记录以评估 C 纤维 ADS 响应于 2 和 10 Hz 的 ×40 刺激，并在 20 nM 河豚毒素/载体存在下重复。通过三相 C 纤维响应的潜伏期（负峰）和宽度（正峰到正峰）的标准化变化来量化数据。在切口前后测量后爪机械缩回阈值和热缩回潜伏期。

结果

切口促进两性 C 纤维 ADS，女性更明显促进。河豚毒素诱导 C 纤维 ADS 的性别和损伤依赖性变化，这些变化在潜伏期和宽度测量之间是不同的。后爪切口在两性中引起相当的机械超敏反应，但在女性中的峰值热超敏反应较少。

结论

后爪切口诱导 C 纤维活性依赖性减慢的性别依赖性变化，这可能导致观察到的峰值热超敏反应的性别差异。这可能反映了性别和切口诱导的 Na _V通道功能表达的差异，这种差异因 C 纤维亚型而异。