Objective Previous studies have shown that the ventrolateral orbital cortex (VLO) is part of the endogenous analgesic system, which consists of an ascending pathway from the spinal cord to the VLO through the thalamic nucleus submedius and a descending pathway to the spinal cord via the periaqueductal gray (PAG).And the GABAergic interneurons tonically depress this antinociceptive pathway via GABAA receptors.The present study examined the role of GABAB receptor, an autoreceptor, in the VLO-evoked antinociception in rats with neuropathic pain and inflammatory pain.Methods The paw withdrawal threshold (PWT) was measured for 60-min in response to mechanical stimulation (von Frey hairs) using the up-down method in a 10-min interval in spared nerve injury (SNI) rats, and the number of flinches and the durations of licking/biting of the affected paw during each 5-min period were record for 60-min as well as the expression of Fos in the spinal dorsal horn was counted by two experimenters blind to the different groups in formalin test model.Results (1) Microinjection ofbaclofen (0.5, 1, 2 μg/0.5 μL), a GABAB receptor agonist, into the VLO attenuated the SNI-induced mechanical allodynia in a dose-dependent manner.This effect was completely blocked by the GABAB receptor antagonist CGP35348 (2.5 μg/0.5 μL).(2) Microinjection of baclofen (2 μg/0.5 μL) into the VLO also decreased the formalin-induced nociceptive behavior and the expression of Fos in the spinal dorsal horn.These effects were also completely reversed by the CGP35348 (2.5 μg/0.5 μL).(3) When CGP35348 was injected alone into the VLO, there was no effect on the SNI-induced mechanical allodynia and formalin-induced nociceptive behavior as well as the expression of Fos in the spinal dorsal horn, suggesting that the blocking effects of CGP35348 on the baclofen-induced inhibition are not a result of facilitation of the nociceptive responses own.Conclusion GABAa receptors are involved in the VLO-evoked antinociception in rats with neuropathic and inflammatory pain.It provides support for the hypothesis that activation of the GABAB receptors inhibit the inhibitory action of GABAergic neuron on the VLO projection neuron leading to activation of the VLO PAG brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal cord level.