The midbrain periaqueductal gray (PAG) is a crucial area involved in the descending pain inhibitory pathway. Using the whole cell patch clamp recording technique in the brain slices containing the PAG, we have proved the cellular mechanism of  mu-opioid-induced disinhibition in vlPAG neurons and the role of K_ATP channels in opioid-mediating antinociception. The PAG is one of dense distributed regions of a novel family member of opioid receptors, the nociceptin/orphanin FQ (N/OFQ) peptide  (NOP) receptor. Using PAG slice preparations, we have characterized the pharmacological profiles of tens of novel ligands of NOP receptors (6) and found there is functional heterogeneity of NOP receptors (3). We also explored the antinociceptive action of orexins (4), a novel hypothalamic neuropeptide family know for their roles in sleep, metabolic and reward regulations. Recently, we revealed a novel supraspinal antinociceptive mechanism mediated by orexin receptor-initiated endocannabinoid signaling in the PAG (1). Besides, we also found TRPV1 channel activation in the PAG can lead to analgesia via mGluR5 receptor-mediated endocannabinoid signaling (2). We are currently elucidating the role(s) of N/OFQ and orexins in the pathogenesis of several neurological and psychiatric disorders, including migraine, Tourette syndrome, schizophrenia, addiction, depression, parkinsonism, Alzheimer's diseases, and sleep disorders. In addition, using a postoperative pain model, we have revealed the role of the a2d subunit of calcium channels in the antinociceptive action of gabapentin (Neurontin) (7). My colleagues and I are also interested in the factors regulating hippocampal synaptic plasticity and learning and memory functions. We have found high-fat diet impairs hippocampal synaptic plasticity and learning in male but not female mice (5).

近期代表著作：

1] Orexins contribute to restraint stress-induced cocaine relapse by endocannabinoid-mediated disinhibition of dopaminergic neurons. Nature Communications 7:12199. DOI: 10.1038/ncomms12199. 2016.  [Abstract]

2] Stress induces analgesia via orexin 1 receptor-initiated endocannabinoid/CB1 signaling in the mouse periaqueductal gray. Neuropharmacology 105:577-586. 2016.  [Abstract]

3] Orexin A induces bidirectional modulation of synaptic plasticity: Inhibiting long-term potentiation but preventing depotentiation. Neuropharmacology 107:168-180. 2016. [Abstract]

4] Impairment of adenylyl cyclase-mediated glutamatergic synaptic plasticity in the periaqueductal gray in a rat model of neuropathic pain. J Physiol 593.13:2955-2973. 2015.  [Abstract]

5] Elevated plasma orexin A levels in a subgroup of patients with schizophrenia associated with fewer negative and disorganized symptoms. Psychoneuroendocrinology 53:1-9. DOI: 10.1016/j.psyneuen.2014.12.012. 2015.  [Abstract]

6] Hypofunction of glutamatergic neurotransmission in the periaqueductal gray contributes to nerve injury-induced neuropathic pain. J Neurosci 33:7825-7836. 2013.  [Abstract]

7] Activation of orexin 1 receptors in the periaqueductal gray of male rats leads to antinociception via retrograde endocannabinoid (2-arachidonoylglycerol)-induced disinhibition. J. Neurosci,31(41): 14600-10. 2011.  [Abstract]

1] Pharmacological characterization of novel NOP receptor ligands in rat PAG slices.

2] Heterogeneity of NOP receptors

3] Clinical implications of nociceptin and orexin A in neurological or psychiatric disorders

4] Antinociceptive mechanisms of orexins and capsaicin in the PAG

5] Interplays among nociceptin, orexins and endocannabinoids in stress-mediated effects

6] Synaptic plasticity changes induced by high-fat diets

1] Patch-clamp whole cell recording setups for brain slices: blind and visualized

2] Extracellular (conventional and multiple channels )and conventional intracellular recording setups for brain slices

3] Pain animal models: postoperative pain, migraine, acute pain, neuropathic pain

4] Radioimmunoassay of N/OFQ and orexin A