Effect of prolonged administration of bovine lactoferrin in neuropathic pain: involvement of opioid receptors, nitric oxide and TNF-alpha.

Objective: This study aimed to investigate the effect of prolonged administration of bovine milk lactoferrin (bLF) on hyperalgesia and allodynia in a rat model of neuropathic pain and to determine the involvement of c-Fos, TNF-alpha, nitric oxide and opioidergic systems in this effect.

Methods: Neuropathic pain was induced in rats by loose ligation of the right sciatic nerve and evaluated by tests measuring the mechanical and thermal hyperalgesia and allodynia. bLF (50, 100, and 200mg/kg) alone or in combination with opioidergic antagonists were administered intraperitoneally to the rats with neuropathic pain. c-Fos and NADPH-d immunocytochemistry and Western blotting for TNF-alpha, iNOS and nNOS were performed in the lumbar spinal cord of rats. Plasma TNF-alpha levels were determined with ELISA.

Results: Prolonged, but not single, administration of bLF produced antihyperalgesic and antiallodynic effects in neuropathic rats. Pretreatment with opioidergic antagonists significantly decreased this effect. Prolonged administration of bLF decreased c-Fos and NADPH-d immunoreactivity and TNF-alpha and iNOS expressions at 50 and 100mg/kg and nNOS expression at 100mg/kg in the lumbar spinal cord of neuropathic rats. Plasma TNF-alpha levels remained unchanged after bLF treatment.

Conclusions: Prolonged administration of bLF exerts antihyperalgesic and antiallodynic effect in neuropathic rats; down-regulation of both TNF-alpha and iNOS expressions and potentiation of opioidergic system in the lumbar spinal cord can contribute to this effect.