Figure 6. Acute injection of morphine (3 mg/kg) on day 5 in animals that received saline over 4 days (vehicle group) did not increase dorsal horn tissue levels of TNF-α (A), IL-1β (B), or IL-6 (C) when compared with animals that received an equivalent volume of its vehicle (naive group).

On the other hand, acute administration of morphine in animals that received repeated administration of morphine (morphine group) led to a significant increase in TNF-α, IL-1β, and IL-6 in dorsal horn tissues. This increase was attenuated by coadministration of morphine over 4 days with l-NAME (10 mg/kg/d), MnTBAP^3– (10 mg/kg/d), or FeTM-4-PyP⁵⁺ (30 mg/kg/d). Results are expressed as mean ± SEM for 12 animals. *P < 0.001 for morphine alone versus vehicle; ^†P < 0.001 for morphine plus drug versus morphine alone.