Connections between EM2-containing terminals and GABA/μ-opioid receptor co-expressing neurons in the rat spinal trigeminal caudal nucleus.
Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect via the μ-opioid receptor (MOR). To provide morphological evidence for the pain control effect of EM2, the synaptic connections between EM2-immunoreactive (IR) axonal terminals and γ-amino butyric acid (GABA)/MOR co-expressing neurons in lamina II of the spinal trigeminal caudal nucleus (Vc) were investigated in the rat. Dense EM2-, MOR- and GABA-IR fibers and terminals were mainly observed in lamina II of the Vc. Within lamina II, GABA- and MOR-neuronal cell bodies were also encountered. The results of immunofluorescent histochemical triple-staining showed that approximately 14.2 or 18.9% of GABA-IR or MOR-IR neurons also showed MOR- or GABA-immunopositive staining in lamina II; approximately 45.2 and 36.1% of the GABA-IR and MOR-IR neurons, respectively, expressed FOS protein in their nuclei induced by injecting formalin into the left lower lip of the mouth. Most of the GABA/MOR, GABA/FOS, and MOR/FOS double-labeled neurons made close contacts with EM2-IR fibers and terminals. Immuno-electron microscopy confirmed that the EM2-IR terminals formed synapses with GABA-IR or MOR-IR dendritic processes and neuronal cell bodies in lamina II of the Vc. These results suggest that EM2 might participate in pain transmission and modulation by binding to MOR-IR and GABAergic inhibitory interneuron in lamina II of the Vc to exert inhibitory effect on the excitatory interneuron in lamina II and projection neurons in laminae I and III.
Department of Nutrition and Food Hygiene, The Fourth Military Medical University Xi'an, China.
Meng-Ying
MY
Li
Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University Xi'an, China.
Zhen-Yu
ZY
Wu
Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University Xi'an, China.
Ya-Cheng
YC
Lu
Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University Xi'an, China.
Jun-Bin
JB
Yin
Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University Xi'an, China.
Jian
J
Wang
Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University Xi'an, China.
Ting
T
Zhang
Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University Xi'an, China.
Yu-Lin
YL
Dong
Department of Nutrition and Food Hygiene, The Fourth Military Medical University Xi'an, China.
Feng
F
Wang
D000818:Animals; D002452:Cell Count; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009842:Oligopeptides / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism* / Q000648:ultrastructure; D017450:Receptors, Opioid, mu / Q000378:metabolism* / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D014275:Trigeminal Caudal Nucleus / Q000166:cytology*
D009842:Oligopeptides; D018079:Receptors, GABA; D017450:Receptors, Opioid, mu; C105294:endomorphin 2
endomorphin 2; inhibitory interneuron; spinal trigeminal caudal nucleus; synapse; γ-amino butyric acid; μ-opioid receptor