Is the response pattern of on- and off-cells in the rostral ventromedial medulla to noxious stimulation independent of stimulation site?

2001 ◽  
Vol 136 (3) ◽  
pp. 394-399 ◽  
Author(s):  
Jens Ellrich ◽  
Coskun Ulucan ◽  
Cathrin Schnell
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.


2014 ◽  
Vol 112 (9) ◽  
pp. 2199-2217 ◽  
Author(s):  
Nabil El Bitar ◽  
Bernard Pollin ◽  
Daniel Le Bars

In thermal neutral condition, rats display cyclic variations of the vasomotion of the tail and paws, synchronized with fluctuations of blood pressure, heart rate, and core body temperature. “On-” and “off-” cells located in the rostral ventromedial medulla, a cerebral structure implicated in somatic sympathetic drive, 1) exhibit similar spontaneous cyclic activities in antiphase and 2) are activated and inhibited by thermal nociceptive stimuli, respectively. We aimed at evaluating the implication of such neurons in autonomic regulation by establishing correlations between their firing and blood pressure, heart rate, and skin and core body temperature variations. When, during a cycle, a relative high core body temperature was reached, the on-cells were activated and within half a minute, the off-cells and blood pressure were depressed, followed by heart rate depression within a further minute; vasodilatation of the tail followed invariably within ∼3 min, often completed with vasodilatation of hind paws. The outcome was an increased heat loss that lessened the core body temperature. When the decrease of core body temperature achieved a few tenths of degrees, sympathetic activation switches off and converse variations occurred, providing cycles of three to seven periods/h. On- and off-cell activities were correlated with inhibition and activation of the sympathetic system, respectively. The temporal sequence of events was as follows: core body temperature → on-cell → off-cell ∼ blood pressure → heart rate → skin temperature → core body temperature. The function of on- and off-cells in nociception should be reexamined, taking into account their correlation with autonomic regulations.


1995 ◽  
Vol 74 (4) ◽  
pp. 1742-1759 ◽  
Author(s):  
H. L. Fields ◽  
A. Malick ◽  
R. Burstein

1. The rostral ventromedial medulla (RVM) participates in the modulation of nociceptive transmission by spinal cord neurons. Previous anatomic studies have demonstrated that RVM neurons project to laminae I, II, and V of the dorsal horn; laminae VII and VIII of the intermediate and ventral horns; the intermediolateral column; and lamina X. The RVM contains at least three physiologically defined classes of neurons, two of which, the ON and the OFF cells, have been implicated in nociceptive modulation. Because these cells classes are intermingled in the RVM, it has not been possible to determine the spinal laminar projection targets of ON and OFF cells by anatomic methods. Therefore in the current study we employed antidromic microstimulation methods to determine the laminar projections of two of the three classes of RVM neurons, the ON and the OFF cells. 2. In lightly anesthetized (with methohexital sodium) rats, single-unit extracellular recordings were made from 48 RVM neurons that were physiologically characterized as ON (30) or OFF (18) cells. The recording locations of 45 of these neurons were recovered. Thirty-seven were found in the nucleus raphe magnus and eight were located near its dorsal and lateral borders. 3. Thirty-two physiologically identified RVM neurons (18 ON and 14 OFF cells) were antidromically activated from the cervical spinal cord using a monopolar stimulating electrode. The stimulating electrode was moved systematically in the white matter until antidromic activation could be produced with currents of < or = 20 microA (6.1 +/- 0.7 microA, mean +/- SE). The points from which minimum currents were required to antidromically activate the neurons were located mainly in the ipsilateral dorsolateral funiculus (DLF) (27 of 32). In a few cases, lowest antidromic threshold currents were found near the border between the DLF and ventrolateral funiculus (VLF) or, rarely, in the VLF itself. In these cases, the cell recordings were found to be near the dorsal boundary of the RVM. 4. While one electrode was used to stimulate the parent axon in the lateral funiculus, a second was used to explore the gray matter for the presence of collateral branches. The identification of a branch was initially determined by an increase in antidromic latency. At the same rostrocaudal plane of the spinal cord, stimulation of the DLF induced an antidromic spike that invaded the neuron earlier than the antidromic spike elicited by stimulation in the gray matter. Collateral branches were confirmed by establishing that the location of the minimum threshold point for antidromic activation of the neurons from the second electrode was in the gray matter, that the minimum current required to antidromically activate the neuron from that point was too low to activate the parent axon in the DLF, and that a collision occurred between the spikes induced by the two stimulating electrodes. 5. In 17 cases, physiologically identified RVM neurons (10 ON and 7 OFF cells) were antidromically activated from the gray matter of the cervical spinal cord using a current of 8.4 +/- 2.1 (SE) microA. Minimum threshold points for antidromic activation were found in laminae I-II (3 ON and 4 OFF cells), lamina V (5 ON and 6 OFF cells), and regions ventral to the lateral reticulated area (3 ON and 2 OFF cells) of the gray matter. As indicated by these numbers, some neurons were antidromically activated from more than one gray matter region. In general, all OFF cells and 9 of 10 ON cells were antidromically activated from low threshold points in either laminae I-II or lamina V. 6. In six cases, neurons were activated from separate points located in two or three different laminae of the gray matter. Three OFF cells were activated from laminae I-II and V, one OFF cell and one ON cell were activated from lamina V and from more ventral points, and one ON cell was activated from laminae I-II and from points ventral to lamina V.


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