The role of descending fibers from the rostral ventromedial medulla in opioid analgesia in rats

2002 ◽  
Vol 449 (1-2) ◽  
pp. 75-84 ◽  
Author(s):  
Annie-Kim Gilbert ◽  
Keith B.J Franklin
Keyword(s):  
Rostral Ventromedial Medulla ◽  
Opioid Analgesia ◽  
Descending Fibers ◽  
Ventromedial Medulla

scholarly journals Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors

2012 ◽  
Vol 107 (4) ◽  
pp. 1210-1221 ◽  
Author(s):  
Thaddeus S. Brink ◽  
Cholawat Pacharinsak ◽  
Sergey G. Khasabov ◽  
Alvin J. Beitz ◽  
Donald A. Simone
Keyword(s):  
Rostral Ventromedial Medulla ◽  
Intraplantar Injection ◽  
Nociceptive Transmission ◽  
Descending Facilitation ◽  
Pain Transmission ◽  
Ventromedial Medulla ◽  
Neurokinin 1 ◽  
Excitatory Responses ◽  
Heat Hyperalgesia

The rostral ventromedial medulla (RVM) is part of descending circuitry that modulates nociceptive processing at the level of the spinal cord. RVM output can facilitate pain transmission under certain conditions such as inflammation, and thereby contribute to hyperalgesia. Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending facilitation of nociception. We showed previously that injection of NK-1 receptor antagonists into the RVM attenuated mechanical and heat hyperalgesia produced by intraplantar injection of capsaicin. Furthermore, intraplantar injection of capsaicin excited ON cells in the RVM and inhibited ongoing activity of OFF cells. In the present studies, we therefore examined changes in responses of RVM neurons to mechanical and heat stimuli after intraplantar injection of capsaicin and determined the role of NK-1 receptors by injecting a NK-1 receptor antagonist into the RVM prior to capsaicin. After capsaicin injection, excitatory responses of ON cells and inhibitory responses of OFF cells evoked by mechanical and heat stimuli applied to the injected, but not contralateral, paw were increased. Injection of the NK-1 antagonist L-733,060 did not alter evoked responses of ON or OFF cells but attenuated the capsaicin-evoked enhanced responses of ON cells to mechanical and heat stimuli with less of an effect on the enhanced inhibitory responses of OFF cells. These data support the notion that descending facilitation from RVM contributes to hyperalgesia and that NK-1 receptors, presumably located on ON cells, play an important role in initiating descending facilitation of nociceptive transmission.

scholarly journals Activation of the Mammalian Target of Rapamycin in the Rostral Ventromedial Medulla Contributes to the Maintenance of Nerve Injury-Induced Neuropathic Pain in Rat

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Jian Wang ◽  
Da-Yun Feng ◽  
Zhi-Hua Li ◽  
Ban Feng ◽  
Han Zhang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Mtor Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Brain Slices ◽  
Rostral Ventromedial Medulla ◽  
Target Of Rapamycin ◽  
Ventromedial Medulla ◽  
Relay Region

The mammalian target of rapamycin (mTOR), a serine-threonine protein kinase, integrates extracellular signals, thereby modulating several physiological and pathological processes, including pain. Previous studies have suggested that rapamycin (an mTOR inhibitor) can attenuate nociceptive behaviors in many pain models, most likely at the spinal cord level. However, the mechanisms of mTOR at the supraspinal level, particularly at the level of the rostral ventromedial medulla (RVM), remain unclear. Thus, the aim of this study was to elucidate the role of mTOR in the RVM, a key relay region for the descending pain control pathway, under neuropathic pain conditions. Phosphorylated mTOR was mainly expressed in serotonergic spinally projecting neurons and was significantly increased in the RVM after spared nerve injury- (SNI-) induced neuropathic pain. Moreover, in SNI rat brain slices, rapamycin infusion both decreased the amplitude instead of the frequency of spontaneous excitatory postsynaptic currents and reduced the numbers of action potentials in serotonergic neurons. Finally, intra-RVM microinjection of rapamycin effectively alleviated established mechanical allodynia but failed to affect the development of neuropathic pain. In conclusion, our data provide strong evidence for the role of mTOR in the RVM in nerve injury-induced neuropathic pain, indicating a novel mechanism of mTOR inhibitor-induced analgesia.

Sign in / Sign up

Export Citation Format

Share Document