A Src family kinase maintains latent sensitization in rats, a model of inflammatory and neuropathic pain.

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.