['Opioids may cause progressive enhancement of pain sensitivity (opioid-induced hyperalgesia [OIH]) and thus, exacerbate existing pain. Animal studies also demonstrate paradoxical OIH with an ultralow dose (ULD, subanalgesic) of opioid; eg, the μ-opioid, morphine. Repeated administration of ULD-morphine resulted in tolerance to ULD-OIH. Prior exposure to ULD-morphine prolonged subsequent morphine antinociception in intact rats (delay of tolerance) and blocked neuropathic pain in nerve-injured rats (no hyperalgesia). Hence, pre-emptive desensitization of the excitatory function of opioid receptors may reduce further activation of a pain facilitatory system exerted by opioid or nerve injury.', 'We determined if ULD-fentanyl (μ-opioid) and U50488H (κ-opioid) also affect post-nerve-injury neuropathy (a rat model of chronic constriction nerve injury [CCI]).', 'Fentanyl (0.5-500 ng/kg) was administered acutely in noninjured rats. Chronic fentanyl (5 ng/kg/day) was initiated either immediately after CCI (day 1-28) or when neuropathy was established (day 7-14) in nerve-injured rats. U50488H (25 μg/kg/day) was given on day 1-28 post-CCI. Saline served as control. Responsiveness was assessed using tail-flick and paw-pressure tests, respectively, in intact and CCI Sprague-Dawley rats of both sexes.', 'ULD-fentanyl evoked pain sensitization in noninjured rats. ULD-OIH was related to dose (inversely), gender (female > male), and was reversed by ketamine. Neuropathy developed after CCI in control (saline) rats. This was not observed in rats of either sex exposed to ULD-fentanyl on day 1-28 post-CCI. Rats treated with ULD-fentanyl from day 7 after CCI exhibited hyperalgesia similar to control rats. U50488H did not block post-CCI neuropathy (regardless of gender).'] Does ultralow dose fentanyl prevent development of chronic neuropathic pain in rats?