Nucleus raphe magnus modulation of response of rat dorsal horn neurons to unmyelinated fiber inputs: partial involvement of serotonergic pathways

1980 ◽  
Vol 44 (6) ◽  
pp. 1039-1057 ◽  
Author(s):  
J. P. Rivot ◽  
A. Chaouch ◽  
J. M. Besson

1. In the rat under N2O-halothane anesthesia, stimulation of the nucleus raphe magnus (NRM) with stimulus parameters similar to those used to obtain analgesia in freely moving animals strongly inhibits the responses of dorsal horn convergent neurons due to A-delta- and C-afferents. 2. Responses to noxious radiant heat were also depressed, and pronounced post-effects were frequently observed. 3. Comparison between coupled sites of stimulation in NRM and in adjacent bulbar reticular formation (BRF) on responses to C-fibers revealed the preeminent effects of NRM; these were systematically encountered (93% of neurons), much more pronounced, and of longer duration. 4. The latency of these inhibitory effects (around 20 ms) suggests the participation of myelinated axons in such descending action and, consequently, we question the involvement of unmyelinated serotonergic fibers. 5. However, descending inhibitory influences from NRM on responses to C-fibers are reduced after 5-hydroxytryptamine (5-HT) depletion by p-chlorophenylalinine (pCPA), thus demonstrating the implication of both serotonergic and nonserotonergic pathways. 6. In addition, after pCPA pretreatment, long-lasting and sustained excitatory effects from NRM were observed in 35% of convergent neurons; their possible origin is discussed.

1994 ◽  
Vol 71 (6) ◽  
pp. 2430-2445 ◽  
Author(s):  
C. Y. Chiang ◽  
J. W. Hu ◽  
B. J. Sessle

1. The aim of this study was to test whether parabrachial area (PBA) stimulation exerts inhibitory influences on the spontaneous activity and responses evoked by skin and deep afferent inputs in trigeminal subnucleus caudalis (Vc) neurons, and to compare these effects with those of nucleus raphe magnus (NRM) stimulation. A total of 92 nonnociceptive and nociceptive Vc neurons was recorded in urethan/alpha-chloralose-anesthetized rats. Each neuron was functionally classified as low-threshold mechanoceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), nociceptive convergent with both skin and deep inputs (S+D), or deep nociceptive (D); the LTM neurons could be subdivided as rapidly adapting (RA) or slowly adapting (SA). Conditioning stimulation was applied to histologically verified sites in PBA and NRM. 2. The spontaneous or evoked activity of all classes of neurons could be inhibited by PBA as well as by NRM stimulation, but generally the incidence and magnitude of inhibition were lower for the LTM neurons. Occasionally, facilitation of neuronal activity was also produced by PBA and NRM stimulation. 3. The spontaneous activity of 11 LTM neurons (6 RA, 5 SA), 13 nociceptive neurons (6 WDR, 7 NS), and 5 D neurons was tested with stimulation of PBA or NRM or both. LTM spontaneous activity was more significantly inhibited by NRM stimulation than by PBA stimulation, whereas both NRM and PBA stimulation had similar and significant inhibitory effects on NS, WDR, and D neurons. 4. The evoked nonnociceptive responses of 28 LTM neurons (16 RA, 12 SA) and of 6 WDR neurons were also tested with stimulation of PBA or NRM or both. The magnitudes of inhibition of the responses produced by PBA conditioning stimulation were statistically significantly less than those induced by NRM conditioning stimulation. 5. The cutaneous and deep nociceptive responses of cutaneous nociceptive neurons (9 NS, 19 WDR) and seven D neurons, respectively, were also tested with PBA and NRM stimulation. There was a significant difference in potency between PBA- and NRM-induced inhibition, but no difference in the magnitude of inhibitory effects among NS, WDR, and D neurons. For both PBA and NRM conditioning stimulation, graded increases in intensities of stimulation produced linear increases in inhibitory effects on nociceptive responses; an increase in stimulation frequency from 5 to 400 Hz also produced increases in inhibition of the nociceptive responses. 6. In five S+D nociceptive convergent neurons, the responses elicited by deep inputs were more powerfully inhibited by PBA stimulation than those elicited by cutaneous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)


1983 ◽  
Vol 50 (6) ◽  
pp. 1433-1445 ◽  
Author(s):  
G. F. Gebhart ◽  
J. Sandkuhler ◽  
J. G. Thalhammer ◽  
M. Zimmermann

The descending inhibition of spinal neuronal responses by focal electrical stimulation in the periaqueductal gray (PAG) or nucleus raphe magnus (NRM) was quantitatively studied and compared in the anesthetized, paralyzed cat. All 60 dorsal horn neurons studied were driven by electrical stimulation of hindlimb cutaneous nerves at strengths supramaximal for activation of A-alpha,delta- and C-fibers, and 52 also responded to noxious radiant heating (50 degrees C, 10 s) of the skin of the foot- or toepads; 8 units had receptive fields in the hairy skin of the hindlimb. All neurons studied also responded to mechanical stimuli; recording sites were located in laminae I-VI of the dorsal horn. The inhibition of spinal neuronal heat-evoked responses by stimulation in the PAG or NRM differed quantitatively when examined on the same spinal neurons. Inhibition of heat-evoked spinal neuronal responses occurred at a lower threshold of stimulation in the NRM than in the PAG. The mean intensity of stimulation in the NRM producing an attenuation to 50% of the control 50 degrees C heat-evoked response was significantly lower than the mean intensity of stimulation in the PAG producing a 50% attenuation of the same spinal units. The mean magnitude of inhibition produced by stimulation in the NRM was significantly greater than that produced on the same spinal units by the same intensity of stimulation in the PAG. However, stimulation in the NRM and PAG produced the same mean percent change in inhibition per 100-microA increase in the intensity of stimulation. Thus, the slopes of the recruitment of descending inhibition from the PAG and the NRM as a function of increasing intensities of stimulation are the same; the lines of recruitment of inhibition are parallel. When examined on the same dorsal horn units, stimulation in the PAG influenced their intensity coding to graded noxious heating of the skin differently than did stimulation in the NRM. The responses of the class 2 and class 3 spinal units examined to increasing temperatures of heat applied to the skin was a monotonic linear function throughout the temperature range studied (42-50 degrees C). Stimulation in the PAG decreased the slope of the stimulus-response function (SRF) without affecting unit thresholds of response, thus influencing the gain control of nociceptive transmission in the dorsal horn. Stimulation in the NRM produced a parallel shift to the right of the SRF, influencing the set point and threshold of response.(ABSTRACT TRUNCATED AT 400 WORDS)


1977 ◽  
Vol 126 (3) ◽  
pp. 441-453 ◽  
Author(s):  
Howard L. Fields ◽  
Allan I. Basbaum ◽  
Charles H. Clanton ◽  
Stuart D. Anderson

1979 ◽  
Vol 42 (6) ◽  
pp. 1527-1537 ◽  
Author(s):  
I. D. Hentall ◽  
H. L. Fields

1. The effect was studied of various conditioning stimuli on the threshold of single C-fibers near their spinal terminals. Spikes were recorded in L6 and L7 dorsal root ganglia of cats. A stimulating electrode in the superficial dorsal horn delivered periodic pulses whose widths were adjusted automatically to near threshold for antidromic spike production. Most units were classified according to their adequate cutaneous stimuli, as C-mechanoreceptors, high-threshold mechanoreceptors, or polymodal nociceptors. 2. Orthodromic activity in all units increased their threshold for up to several minutes; the maximum and rate of decay depended on the amount of activity. This phenomenon parallels the hyperpolarizing afterpotential of C-fibers in peripheral nerve and, we suggest, is probably due to the aftereffect of impulses. 3. Cutaneous conditioning stimuli were applied for 10-20 s near the receptive fields of tested units, but without activating them. During the brushing of skin hair, all threshold changes were decreases; during pinching most changes were increases; during noxious heating the numbers of increases and decreases were similar. It will be necessary to analyze the responses of postsynaptic cells in order to know the physiological significance of these threshold changes. 4. Stimulation in the nucleus raphe magnus caused in half the units higher intraspinal thresholds. If this result is causally related to the previously reported inhibition of neuronal responses in the dorsal horn by the nucleus raphe magnus (NRM), then increased thresholds could reflect either direct presynaptic inhibition or facilitation of inhibitory connections. 5. No correlation between receptive-field classification and the response of terminals to natural cutaneous stimulation or stimulation of the NRM could be discovered. However, the terminals of all kinds of C-fibers differ from A-fibers in their reaction to noxious cutaneous and NRM stimulation, suggesting they are subject to a different system of control.


1997 ◽  
Vol 77 (5) ◽  
pp. 2831-2835 ◽  
Author(s):  
B. J. Workman ◽  
B. M. Lumb

Workman, B. J. and B. M. Lumb. Inhibitory effects evoked from the anterior hypothalamus are selective for the nociceptive responses of dorsal horn neurons with high- and low-threshold inputs. J. Neurophysiol. 77: 2831–2835, 1997. The aim of the present study was to examine the selectivity of descending control of nociceptive information in the spinal dorsal horn following neuronal activation at “pressor” sites in the anterior hypothalamus. Extracellular single-unit activity was recorded from 11 dorsal horn neurons in the lower lumbar spinal cord of anesthetized rats. Neurons selected for investigation were those that responded to noxious (pinch and radiant heat >46°C) and nonnoxious (prod, stroke, and/or brush) stimulation within their cutaneous receptive fields on the ipsilateral hind paw. These are referred to as Class 2 neurons. Micropipettes were inserted stereotaxically into the anterior hypothalamus at sites where injection of the excitatory amino acidl-homocysteic acid (l-HCA) evoked increases in arterial blood pressure. The effects of microinjection of l-HCA at “pressor” sites in the anterior hypothalamus were then tested on the responses of Class 2 neurons to noxious and nonnoxious stimulation of their excitatory receptive fields. The high-threshold (pinch and/or radiant heat) responses of 7/7 Class 2 neurons tested were inhibited by an average of 66.3 ± 8.8% (mean ± SE) by neuronal activation at hypothalamic pressor sites. The low-threshold (prod) responses of 10/10 Class 2 neurons tested were not inhibited by neuronal activation at hypothalamic pressor sites; in 6 of these cells the response to low-intensity stimulation was increased by between 4 and 20%. Control injections of the inhibitory amino acid γ-aminobutyric acid (GABA) at the same hypothalamic pressor sites had no significant effects on arterial blood pressure or neuronal activity. With regard to sensory processing in the spinal cord, these data suggest that descending inhibitory control that originates from neurons in pressor regions of the anterior hypothalamus is highly selective for nociceptive inputs to Class 2 neurons.


1987 ◽  
Vol 58 (2) ◽  
pp. 327-341 ◽  
Author(s):  
J. Sandkuhler ◽  
Q. G. Fu ◽  
M. Zimmermann

1. The spinal pathways for tonic and stimulation-produced descending inhibition of spinal nociceptive neurons were investigated in anesthetized paralyzed cats. Reversible circumscribed blocks were produced at various depths in the lateral funiculi (LF) at L1-L2 using the microinjection of the local anesthetic lidocaine. The total amount of tonic descending inhibition in the absence of LF blocks was evaluated by monitoring the spinal neuronal activity during reversible spinalization by cold block and compared with the activity of the same neuron during LF blocks. Stimulation-induced descending inhibition of neuronal responses to noxious skin heating was produced by bipolar focal electrical stimulation in the periaqueductal gray (PAG) or nucleus raphe magnus (NRM) and compared with the inhibition of the same neurons during LF blocks. The relative significance of ipsi- and contralateral pathways in the dorsal, medial, or ventral aspects of the lateral funiculi for these types of descending inhibition are quantitatively described. 2. All 35 lumbar spinal dorsal horn neurons studied responded to noxious and innocuous mechanical and noxious thermal stimuli applied within the receptive fields on the glabrous skin of the hindlimb. Responses to noxious skin stimuli (50 degrees C, 10 s at 3-min intervals) were constant over time and served as a parameter to evaluate tonic and stimulation-produced descending inhibition. All neurons also responded to electrical stimulation of hindlimb cutaneous nerves supramaximal for the activation of A-beta-, delta-, and C-fibers. Neurons were located in laminae I-VI of the dorsal horn at L5-L7 levels. LF blocks were produced by the microinjection of 1 microliter lidocaine at each of one to six sites in the ipsilateral and/or contralateral LF 500, 1,500, and/or 2,500 microns below cord surface. 3. LF blocks ipsilateral to the recording sites in the cord significantly reduced tonic inhibition, with blocks in the dorsal part of the LF [i.e., the dorsolateral funiculus (DLF)] being equally effective to complete LF blocks. Stimulation-produced inhibition from PAG or NRM was, however, not significantly affected by ipsilateral LF blocks. 4. Contralateral LF blocks significantly reduced stimulation-produced descending inhibition and failed to affect tonic descending inhibition. Ventral LF blocks attenuated inhibition from the PAG but not from NRM, whereas DLF blocks were more effective on inhibition from the NRM. 5. Bilateral LF blocks significantly reduced tonic as well as stimulation-produced descending inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)


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