Sex differences in carbamazepine effects in a rat model of trigeminal neuropathic pain

Carbamazepine (CBZ) represents the first-line treatment for trigeminal neuralgia, a condition of facial pain that affects mainly women. The chronic constriction of the infraorbital nerve (CCI-ION) is a widely used model to study this condition, but most studies do not include females. Thus, this study aimed to characterize sensory and affective changes in female rats after CCI-ION and compare the effect of CBZ in both sexes. Mechanical allodynia was assessed 15 days after CCI-ION surgery in rats treated with CBZ (10 and 30 mg/kg, i.p.) or vehicle, together with the open-field test. Independent groups were tested on the Conditioned Place Preference (CPP) paradigm and ultrasonic vocalization (USV) analysis. Blood samples were collected for dosage of the main CBZ metabolite. CBZ at 30 mg/kg impaired locomotion of CCI-ION male and sham and CCI-ION female rats and resulted in significantly higher plasma concentrations of 10-11-EPX-CBZ in the latter. Only male CCI-ION rats showed increased facial grooming which was significantly reduced by CBZ at 10 mg/kg. CBZ at 10 mg/kg significantly reduced mechanical allodynia and induced CPP only in female CCI-ION rats. Also, female CCI-ION showed reduced emission of appetitive USV but did not show anxiety-like behavior. In conclusion, male and female CCI-ION rats presented differences in the expression of the affective-motivational pain component and CBZ was more effective in females than males. Further studies using both sexes in trigeminal neuropathic pain models are warranted for a better understanding of potential differences in the pathophysiological mechanisms and efficacy of pharmacological treatments.