Milnacipran, a
serotonin and noradrenalin reuptake inhibitor (
SNRI), is efficacious in rodents in various models of acute or
chronic pain (traumatic, neuropathic, inflammatory, visceral). However, its activity against arthritic
pain has never been explored. Here, we assessed the activity of acute treatment with
milnacipran in a polyarthritic rat model. Rats were injected in the tail base with complete
Freund's adjuvant to induce a state of
polyarthritis.
Analgesic effects of acute treatment with intraperitoneal administration of
milnacipran were then evaluated, using the Randall-Selitto model, against two levels of pressure applied to both hind paws (a lower one, addressing
mechanical allodynia and a higher one, addressing
mechanical hyperalgesia). The other
SNRI duloxetine and the nonsteroidal anti-inflammatory drug
indomethacin were tested as positive controls.
Milnacipran was significantly and dose dependently active against the decrease of paw withdrawal threshold produced by complete
Freund's adjuvant for low (minimum effective dose=5 mg/kg, range tested: 2.5-10 mg/kg) and high (minimum effective dose=10 mg/kg, range tested: 5-20 mg/kg)-pressure levels.
Duloxetine (20 mg/kg, intraperitoneally) was significantly active against low pressure only.
Indomethacin (3 mg/kg per os) was efficacious against both pressure levels. These rodent data suggest that
milnacipran should be efficacious in painful conditions associated with chronic inflammatory states, such as
arthritis.