Compensatory Activation of Cannabinoid CB2 Receptor Inhibition of GABA Release in the Rostral Ventromedial Medulla in Inflammatory Pain

The current study has investigated the involvement of periaqueductal gray (PAG) metabotropic glutamate subtype 7 and 8 receptors (mGluR7 and mGluR8) in modulating rostral ventromedial medulla (RVM) ongoing and tail flick–related on and off cell activities. Our study has also investigated the role of PAG mGluR7 on thermoceptive threshold and PAG glutamate and GABA release. Intra-ventrolateral PAG ( S)-3,4-dicarboxyphenylglycine [( S)-3,4-DCPG (2 and 4 nmol/rat)] or N,N I-dibenzhydrylethane-1,2-diamin dihydrochloride (AMN082, (1 and 2 nmol/rat), selective mGluR8 and mGluR7 agonists, respectively, caused opposite effects on the ongoing RVM on and off cell activities. Tail flick latency was increased or decreased by ( S)-3,4-DCPG or AMN082 (2 nmol/rat), respectively. ( S)-3,4-DCPG reduced the pause and delayed the onset of the off cell pause. Conversely, AMN082 increased the pause and shortened the onset of off cell pause. ( S)-3,4-DCPG or AMN082 did not change the tail flick-induced onset of on-cell peak firing. The tail flick latency and its related electrophysiological effects induced by ( S)-3,4-DCPG or AMN082 were prevented by (RS)-α-methylserine-o-phosphate (100 nmol/rat), a group III mGluR antagonist. Intra-ventrolateral PAG perfusion with AMN082 (10 and 25 μM), decreased thermoceptive thresholds and glutamate extracellular levels. A decrease in GABA release was also observed. These results show that stimulation of PAG mGluR8 or mGluR7 could either relieve or worsen pain perception. The opposite effects on pain behavior correlate with the opposite roles played by mGluR7 and mGluR8 on glutamate and GABA release and the ongoing and tail flick-related activities of the RVM on and off cells.

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Rostral ventromedial medulla μ, but not κ, opioid receptors are involved in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model

Brain Research ◽

10.1016/j.brainres.2011.04.037 ◽

2011 ◽

Vol 1395 ◽

pp. 38-45 ◽

Cited By ~ 17

Author(s):

Yu Zhang ◽

Aihui Li ◽

Lixing Lao ◽

Jiajia Xin ◽

Ke Ren ◽

...

Keyword(s):

Opioid Receptors ◽

Rat Model ◽

Inflammatory Pain ◽

Rostral Ventromedial Medulla ◽

Ventromedial Medulla

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Electroacupuncture Inhibits the Activation of p38MAPK in the Central Descending Facilitatory Pathway in Rats with Inflammatory Pain

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/7531060 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Man-Li Hu ◽

Fei-Yan Zhou ◽

Jing-Jing Liu ◽

Yi Ding ◽

Ju-Ming Zhong ◽

...

Keyword(s):

Inflammatory Pain ◽

Spinal Cord Dorsal Horn ◽

Rostral Ventromedial Medulla ◽

Saline Injection ◽

Paw Edema ◽

Pain Model ◽

Withdrawal Threshold ◽

Ventromedial Medulla ◽

Mitogen Activated Protein ◽

Spinal Cord Dorsal

The mitogen-activated protein kinases (MAPKs), especially p38MAPK, play a pivotal role in chronic pain. Electroacupuncture (EA) relieves inflammatory pain underlying the descending pathway, that is, the periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), and the spinal cord dorsal horn (SCDH). However, whether EA antagonizes inflammatory pain through regulation of p38MAPK in this descending facilitatory pathway is unclear. Complete Freund’s adjuvant (CFA) was injected into the hind paw of rats to establish inflammatory pain model. EA was administrated for 30 min at Zusanli and Kunlun acupoints at 0.5, 24.5, 48.5, and 72.5 h, respectively. The paw withdrawal threshold (PWT), paw edema, and Phosphor-p38MAPK-Immunoreactivity (p-p38MAPK-IR) cells were measured before (0 h) and at 1, 3, 5, 7, 25, and 73 h after CFA or saline injection. EA increased PWT at 1, 3, 25, and 73 h and inhibited paw edema at 25 and 73 h after CFA injection. Moreover, the increasing number of p-p38MAPK-IR cells which was induced by CFA was suppressed by EA stimulation in PAG and RVM at 3 and 5 h and in SCDH at 5, 7, 25, and 73 h. These results suggest that EA suppresses inflammation-induced hyperalgesia probably through inhibiting p38MAPK activation in the descending facilitatory pathway.

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