Co-application of lidocaine and QX-572 induces divergent pain behaviours in mice

Abstract

Objectives We investigated the analgesic effects of lidocaine (LDC) and lidocane derivative, QX-572, co-application on the evoked pain behaviour (complete Freund's Adjuvant (CFA)-induced) and spontaneous pain behaviour (formalin-induced) in mice. Methods The experiments were performed using adult male Kunming mice. Formalin-induced acute pain model and CFA-induced chronic pain model was established by injecting formalin and CFA, respectively. Separate injections of LDC and QX-572, or co-injection of LDC and QX-572, were performed to observe the differences in neurobehavioural responses, paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT). Key findings QX-572 injection alone did not influence PWL and MWT, but injection of LDC alone led to a substantial, but short-lived, elevation in PWL and MWT (45 min). Co-injection of LDC and QX-572, however, resulted in a significant increase in PWL and MWT (120 min) compared with the LDC group. Injection of LDC and QX-572 combination in the adjacent sciatic nerve also produced a long-lasting sensory-specific nerve block. Additionally, intraplantar co-injection of LDC and QX-572 combination inhibited spontaneous pain in formalin-treated mice, but did not detectably attenuated hyperalgesia and allodynia in CFA-treated mice. Conclusions Our results provide evidence that QX-572 induced sensory-selective blockade and co-injection of QX-572 and LDC enhance pain blockade, as evident from formalin-treated mice.