Effect of pregabalin on nociceptive thresholds and immune responses in a mouse model of incisional pain

Abstract

Background It is known that some analgesics as well as pain can affect the immune system. The aim of this study was to investigate the analgesic effect and immunomodulation of pregabalin (PGB) in a mouse incisional pain model. Methods A postoperative pain model was induced by hind paw plantar incision in male BALB/c mice. Mice were randomly divided into four groups (n = 8) a saline-treated incision (incision), PGB-treated incision (PGB-incision), sham controls without incision or drug treatment (control), and a PGB-treated control (PGB-control). In the PGB treated groups, PGB was administered intraperitoneally (IP) 30 minutes before and 1 hour after the plantar incision. Changes of the mechanical nociceptive thresholds following incision were investigated. Mice were euthanized for spleen harvesting 12 hours after the plantar incision, and natural killer (NK) cytotoxicity to YAC 1 cells and lymphocyte proliferation responses to phytohemagglutinin were compared among these four groups. Results Mechanical nociceptive thresholds were decreased after plantar incision and IP PGB administration recovered these decreased mechanical nociceptive thresholds ( P < 0.001). NK activity was increased by foot incision, but NK activity in the PGB-incision group was significantly lower than that in the Incision group ( P < 0.001). Incisional pain increased splenic lymphocyte proliferation, but PGB did not alter this response. Conclusions Incisional pain alters cell immunity of the spleen in BALB/c mice. PGB showed antinocieptive effect on mouse incisional pain and attenuates the activation of NK cells in this painful condition. These results suggest that PGB treatment prevents increases in pain induced NK cell activity.

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

“…Note that the plasma concentration two hours after i.p. administration of 30 mg/kg to mice is 7.7 μg/mL 73 , which corresponds to 48 μM, and this exceeds the affinity of pregabalin for its primary targets alpha-2-delta-1 and alpha-2-delta-2 74 . Although reflexive pain-response alleviation after pregabalin administration was described in RIM3 rats 15 , 33 , 75 , the present study first describes the antihyperalgesic effect of pregabalin in the RIM6 and ASI model in the mouse, thus validating both models as suitable for use in pharmacological studies addressing the alleviation of sensory, nociplastic/FMS pain-related behaviors.…”