Latent sensitization is a long-term model of chronic pain in which hyperalgesia is continuously suppressed by opioid receptors, as demonstrated by the induction of mechanical allodynia by opioid antagonists. Different intracellular signals may mediate the initiation, maintenance and expression of latent sensitization. Our criterion for the involvement of a signal in the maintenance of latent sensitization is that inhibitors should permanently eliminate the allodynia produced by an opioid antagonist. We hypothesized that Src family kinases (SFKs) maintain latent sensitization and tested this hypothesis by inducing latent sensitization in rats with complete Freund’s adjuvant (CFA) or spared nerve injury. After measures of mechanical allodynia returned to baseline, vehicle or the SFK inhibitor PP2 were injected intrathecally. The opioid antagonist naltrexone injected intrathecally 15 min later produced allodynia in control rats but not in rats injected with PP2. Vehicle or PP2 were injected daily for two more days and naltrexone was injected five days later. Again, naltrexone induced allodynia in the control rats but not in the rats injected with PP2. Results were similar when latent sensitization was induced with CFA or spared nerve injury. We concluded that an SFK, likely Fyn, maintains latent sensitization induced by inflammation or nerve injury.

潜在致敏是一种慢性疼痛的长期模型，其中痛觉过敏被阿片受体持续抑制，如阿片拮抗剂诱导机械性异常性疼痛所证明的那样。不同的细胞内信号可能介导潜在致敏的启动、维持和表达。我们关于信号参与维持潜在致敏的标准是抑制剂应永久消除阿片类拮抗剂产生的异常性疼痛。我们假设 Src 家族激酶 (SFK) 维持潜在致敏作用，并通过在完全弗氏佐剂 (CFA) 或未受神经损伤的大鼠中诱导潜在致敏作用来测试这一假设。机械异常性疼痛测量值恢复至基线后，鞘内注射媒介物或 SFK 抑制剂 PP2。 15 分钟后，鞘内注射阿片拮抗剂纳曲酮，在对照大鼠中产生异常性疼痛，但在注射 PP2 的大鼠中则没有。连续两天每天注射赋形剂或PP2，五天后注射纳曲酮。同样，纳曲酮在对照大鼠中引起异常性疼痛，但在注射 PP2 的大鼠中则没有。当用 CFA 诱导潜在致敏或避免神经损伤时，结果相似。我们得出的结论是，SFK（可能是 Fyn）保持着由炎症或神经损伤引起的潜在致敏作用。