Src family kinases maintain latent sensitization, a model of inflammatory and neuropathic pain

Abstract

Latent sensitization is a long-term model of chronic pain in which hyperalgesia is continuously suppressed by opioid receptors. This is 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 it 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 in rats with latent sensitization induced by complete Freunds adjuvant (CFA) or by spared nerve injury. After measures of mechanical allodynia returned to baseline, the SFK inhibitor PP2 or vehicle were injected intrathecally. The opioid antagonist naltrexone injected intrathecally 15 min later produced allodynia in control rats but not in rats injected with PP2. PP2 or vehicle 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 either with CFA or spared nerve injury. We concluded that an SFK, likely Fyn, maintains latent sensitization induced by inflammation or nerve injury. PerspectiveThis article presents evidence that a Src family kinase, likely Fyn, maintains latent sensitization induced by inflammation or nerve injury. If latent sensitization is a valid model of chronic pain, inhibiting its maintenance with Src family kinase inhibitors may cure chronic pain.