Responses of neurons in rostral ventromedial medulla to nociceptive stimulation of craniofacial region and tail in rats

2021 ◽  
pp. 147539
Author(s):  
Jing-Shi Tang ◽  
Chen Yu Chiang ◽  
Jonathan O. Dostrovsky ◽  
Dongyuan Yao ◽  
Barry J. Sessle
2014 ◽  
Vol 111 (11) ◽  
pp. 2196-2209 ◽  
Author(s):  
Francesca Rossi ◽  
Ida Marabese ◽  
Maria De Chiaro ◽  
Serena Boccella ◽  
Livio Luongo ◽  
...  

The present study investigated the role of metabotropic glutamate receptor subtype 8 (mGluR8) in the dorsal striatum (DS) in modulating thermonociception and rostral ventromedial medulla (RVM) ON and OFF cell activities in conditions of neuropathic pain induced by spared nerve injury (SNI) of the sciatic nerve in rats. The role of DS mGluR8 on mechanical allodynia was also investigated. Intra-DS ( S)-3,4-dicarboxyphenylglycine [( S)-3,4-DCPG], a selective mGluR8 agonist, did not modify the activity of the ON and OFF cells in sham-operated rats. In SNI rats, which showed a reduction of the mechanical withdrawal threshold, intra-DS microinjection of ( S)-3,4-DCPG inhibited the ongoing and tail flick-evoked activity of the ON cells while increasing the activity of the OFF cells. AZ12216052, a selective mGluR8 positive allosteric modulator (PAM), behaved like ( S)-3,4-DCPG in increasing tail flick latency and OFF cell activity and decreasing ON cell activity in SNI rats only but was less potent. VU0155041, a selective mGluR4 PAM, was ineffective in changing thermal nociception and ON and OFF cell activity in both sham-operated and SNI rats. ( S)-3,4-DCPG did not change mechanical withdrawal threshold in sham-operated rats but increased it in SNI rats. Furthermore, a decreased level of mGluR8 gene and immunoreactivity, expressed on GABAergic terminals, associated with a protein increase was found in the DS of SNI rats. These results suggest that stimulation of mGluR8 inhibits thermoceptive responses and mechanical allodynia. These effects were associated with inhibition of ON cells and stimulation of OFF cells within RVM.


2015 ◽  
Vol 113 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Sergey G. Khasabov ◽  
Patrick Malecha ◽  
Joseph Noack ◽  
Janneta Tabakov ◽  
Keiichiro Okamoto ◽  
...  

The rostral ventromedial medulla (RVM) projects to the medullary and spinal dorsal horns and is a major source of descending modulation of nociceptive transmission. Traditionally, neurons in the RVM are classified functionally as ON, OFF, and NEUTRAL cells on the basis of responses to noxious cutaneous stimulation of the tail or hind paw. ON cells facilitate nociceptive transmission, OFF cells are inhibitory, whereas NEUTRAL cells are unresponsive to noxious stimuli and their role in pain modulation is unclear. Classification of RVM neurons with respect to stimulation of craniofacial tissues is not well defined. In isoflurane-anesthetized male rats, RVM neurons first were classified as ON (25.5%), OFF (25.5%), or NEUTRAL (49%) cells by noxious pinch applied to the hind paw. Pinching the skin overlying the temporomandibular joint (TMJ) altered the proportions of ON (39.2%), OFF (42.2%), and NEUTRAL (19.6%) cells. To assess the response of RVM cells to specialized craniofacial inputs, adenosine triphosphate (ATP; 0.01–1 mM) was injected into the TMJ and capsaicin (0.1%) was applied to the ocular surface. TMJ and ocular surface stimulation also resulted in a reduced proportion of NEUTRAL cells compared with hind paw pinch. Dose-effect analyses revealed that ON and OFF cells encoded the intra-TMJ concentration of ATP. These results suggest that somatotopy plays a significant role in the functional classification of RVM cells and support the notion that NEUTRAL cells likely are subgroups of ON and OFF cells. It is suggested that a portion of RVM neurons serve different functions in modulating craniofacial and spinal pain conditions.


Cephalalgia ◽  
2019 ◽  
Vol 39 (13) ◽  
pp. 1720-1727 ◽  
Author(s):  
Laura H Schulte ◽  
Kuan-Po Peng

Aim To describe neuronal networks underlying commonly reported migraine premonitory symptoms and to discuss how these might precipitate migraine pain. Background Migraine headache is frequently preceded by a distinct and well characterized premonitory phase including symptoms like yawning, sleep disturbances, alterations in appetite and food intake and hypersensitivity to certain external stimuli. Recent neuroimaging studies strongly suggest the hypothalamus as the key mediator of the premonitory phase and also suggested alterations in hypothalamic networks as a mechanism of migraine attack generation. When looking at the vast evidence from basic research within the last decades, hypothalamic and thalamic networks are most likely to integrate peripheral influences with central mechanisms, facilitating the precipitation of migraine headaches. These networks include sleep, feeding and stress modulating centers within the hypothalamus, thalamic pathways and brainstem centers closely involved in trigeminal pain processing such as the spinal trigeminal nucleus and the rostral ventromedial medulla, all of which are closely interconnected. Conclusion Taken together, these networks represent the pathophysiological basis for migraine premonitory symptoms as well as a possible integration site of peripheral so-called “triggers” with central attack facilitating processes.


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