Perineural Treatment with High Mobility Group Box-1 Monoclonal Antibody Prevents Initiation of Pain-Like Behaviors in Female Mice with Trigeminal Neuropathy.

Post-traumatic trigeminal neuropathy (PTTN) is a type of chronic pain caused by damage to the trigeminal nerve. A previous study reported that pretreatment with anti-high mobility group box-1 (HMGB1) neutralizing antibodies (nAb) prevented the onset of PTTN following distal infraorbital nerve chronic constriction injury (dIoN-CCI) in male mice. Clinical evidence indicates a high incidence of PTTN in females. Although our previous study found that perineural HMGB1 is crucial in initiation of PTTN in male mice, it is currently unknown whether HMGB1 is also involved in the pathogenesis of PTTN in female mice. Therefore, in the current study, we examined the effect of anti-HMGB1 nAb on pain-like behavior in female mice following dIoN-CCI surgery. We found that dIoN-CCI surgery enhanced reactivity to mechanical and cold stimuli in female mice, which was suppressed by treatment with anti-HMGB1 nAb. Moreover, the increase in macrophages after dIoN-CCI was significantly attenuated by pretreatment with anti-HMGB1 nAb. Furthermore, anti-HMGB1 nAb treatment inhibited microglial activation in the trigeminal spinal tract nucleus. These data suggest that HMGB1 also plays a crucial role in the onset of PTTN after nerve injury in female mice. Thus, anti-HMGB1 nAb could be a novel therapeutic agent for inhibiting the onset of PTTN in female and male mice.

Mirogabalin alleviates nociceptive hypersensitivity without causing sedation in a mouse model of post-traumatic trigeminal neuropathy.

Post-traumatic trigeminal neuropathy (PTTN) is a chronic sensory disorder that afflicts patients with nerve injury caused by orofacial and dental surgery or cervicofacial trauma. Currently, effective treatment strategies for PTTN are lacking, and patients treated with conventional drugs for PTTN experience adverse effects such as drowsiness and drug addiction. In the present study, we investigated whether mirogabalin, a novel gabapentinoid, could be an effective treatment for PTTN induced by distal infraorbital nerve chronic constriction injury (dIoN-CCI) in the mouse. Increased facial grooming time and hyper-responsiveness to acetone were observed in dIoN-CCI mice. These pain-related behaviors were attenuated by intraperitoneal injection of mirogabalin. In particular, mirogabalin significantly diminished the increase in facial grooming time. The analgesic effect of mirogabalin injection started 45 min after the injection and persisted for 6 h. Additionally, 10 mg/kg mirogabalin did not affect locomotor activity in the open field test, suggesting that it does not cause sedation. Together, the current findings suggest that mirogabalin could be a valuable therapeutic drug for PTTN following orofacial surgeries without sedative side effects.