Parabrachial area: electrophysiological evidence for an involvement in cold nociception

1996 ◽  
Vol 75 (5) ◽  
pp. 2099-2116 ◽  
Author(s):  
L. Menendez ◽  
H. Bester ◽  
J. M. Besson ◽  
J. F. Bernard

1. Thirty-five percent of 120 neurons recorded extracellularly in the parabrachial (PB) area of anesthetized rats responded to a peripheral cold stimulus (0 degrees C). The cold-sensitive neurons were located in the lateral PB area, and most of those exhibiting a strong response to cold stimuli were inside or in close vicinity to the area receiving a high density of projections from superficial neurons of the dorsal horn. 2. The receptive fields for cold stimulation often were restricted to one or two parts of the body with a contralateral predominance for the limbs. No side predominance was observed for the face. 3. From a low spontaneous activity (10th percentile < median < 90th percentile: 0.1 < 1.5 < 5 Hz), the PB neurons responded to cold noxious stimuli (0 degree C water bath or waterjet, 20 s), without observable delay, with a sustained discharge. The mean maximal response to the stimulus was 16.1 +/- 1.2 Hz (mean +/- SE; n = 42). 4. About one-half (45%) of these cold-sensitive neurons were activated specifically by cold stimulation and did not respond or were inhibited by noxious heat and/or pinch. The remaining (55%) cold-sensitive neurons were also driven by heat and/or pinch. 5. The cold-sensitive neurons exhibited a clear capacity to encode cold stimuli in the noxious range: the stimulus-response function was always positive and monotonic from 30 to 0 degrees C; the mean curve was linear between 20 and 0 degrees C before plateauing between 0 to -10 degrees C; the mean threshold to cold stimulation was 17.1 +/- 1 degrees C (n = 21) and the mean t50 was 10.7 +/- 1.1 degrees C (n = 13). 6. The cold-sensitive neurons responded to intense transcutaneous electrical stimulation with an early and/or a late peak of activation, the latencies of which were in the 15-50 ms and 80-170 ms ranges (n = 8), respectively, i.e., compatible with the activation of A delta and C fibers. Interestingly, the cold-specific neurons predominantly responded with a late peak, suggesting these neurons were primarily driven by peripheral C fibers. 7. The intravenous injection of morphine depressed the responses of PB neurons to cold noxious stimuli in a dose-related (1, 3, and 9 mg/kg) and naloxone reversible fashion. The ED50 value was estimated approximately 2 mg/kg. Furthermore, two populations of neurons could be separated according to their morphine sensitivity. 8. It is concluded that PB cold-nonspecific neurons could be involved in affective-emotional, autonomic and neuroendocrine reactions in response to noxious cold events. The PB cold-specific neurons could be, in addition, involved in some thermoregulatory processes.

2000 ◽  
Vol 83 (4) ◽  
pp. 2239-2259 ◽  
Author(s):  
Hervé Bester ◽  
Victoria Chapman ◽  
Jean-Marie Besson ◽  
Jean-François Bernard

Single-unit extracellular recordings of spino-parabrachial (spino-PB) neurons ( n = 53) antidromically driven from the contralateral parabrachial (PB) area were performed in the lumbar cord in anesthetized rats. All the spino-PB neurons were located in the lamina I of the dorsal horn. Their axons exhibited conduction velocities between 2.8 and 27.8 m/s, in the thin myelinated fibers range. They had an extremely low spontaneous activity (median = 0.064 Hz) and a small excitatory receptive field (≤2 toes or pads). They were all activated by both peripheral A (mainly Aδ) and C fibers after intense transcutaneous electrical stimulation. Their discharge always increased in response to noxious natural stimuli of increasing intensities. The great majority (75%) of spino-PB neurons were nociceptive specific, i.e., they were excited only by noxious stimuli. The remaining (25%) still were excited primarily by noxious stimuli but also responded moderately to innocuous stimuli. Almost all spino-PB neurons (92%, 49/53) were activated by both mechanical and heat noxious stimuli. Among them, 35% were in addition moderately activated by noxious cold (thresholds between +20 and −10°C). Only (8%, 4/53) responded exclusively to noxious heat. Spino-PB neurons clearly encoded the intensity of mechanical ( n = 39) and thermal ( n = 38) stimuli in the noxious range, and most of the individual stimulus-response functions were monotonic and positive up to 40/60 N · cm−2 and 50°C, respectively. For the mechanical modality, the mean threshold was 11.5 ± 1.25 N · cm−2 (mean ± SE), the response increased almost linearly with the logarithm of the pressure between 10 and 60 N · cm−2, the mean p 50(pressure evoking 50% of the maximum response) and the maximum responsiveness were: 30 ± 2.4 N · cm−2 and 40.5 ± 5 Hz, respectively. For the thermal modality, the mean threshold was 43.6 ± 0.5°C, the mean curve had a general sigmoid aspect, the steepest portion being in the 46–48°C interval, the mean t 50 and the maximum responsiveness were: 47.4 ± 0.3°C and 40 ± 4.4 Hz, respectively. Most of the spino-PB neurons tested (13/16) had their noxiously evoked responses clearly inhibited by heterotopic noxious stimuli. The mean response to noxious stimuli during heterotopic stimuli was 31.7 ± 6.1% of the control response. We conclude that the nociceptive properties of the lamina I spino-PB neurons are reflected largely by those of PB neurons that were suggested to be involved in autonomic and emotional/aversive aspects of pain.


1990 ◽  
Vol 63 (3) ◽  
pp. 473-490 ◽  
Author(s):  
J. F. Bernard ◽  
J. M. Besson

1. Neurons were recorded in the parabrachial (PB) area, located in the dorsolateral region of the pons (with the use of extracellular micropipette), in the anesthetized rat. Parabrachioamygdaloid (PA) neurons (n = 67) were antidromically identified after stimulation in the centralis nucleus of the amygdala (Ce). The axons of these neurons exhibit a very slow conduction velocity, between 0.26 and 1.1 m/s, i.e., in the unmyelinated range. 2. These PA neurons were located in a restricted region of the PB area: the subnuclei external lateral (PBel) and external medial (PBem). A relative somatotopic organization was found in this region. 3. These units were separated into two groups: 1) a group of nociceptive-specific (NS) neurons (69%), which responded exclusively to noxious stimuli, and 2) a group of nonresponsive (NR) neurons (31%). 4. The NS neurons exhibited low or lacked spontaneous activity. They responded exclusively to mechanical (pinch or squeeze) and/or thermal (waterbath or waterjet greater than 44 degrees C) noxious stimuli with a marked and sustained activation with a rapid onset and generally without afterdischarge. Noxious thermal stimuli generally induced a stronger response than the noxious mechanical stimuli. These neurons exhibited a clear capacity to encode thermal stimuli in the noxious range: 1) the stimulus-response function was always positive and monotonic; 2) the slope of the curve progressively increased up to a maximum where it was very steep, then the steepness of the slope decreased close to the maximum response; and 3) the mean threshold was 44.1 +/- 2 degrees C, and the point of steepest slope of the mean curve was around 47 degrees C. 5. The excitatory receptive fields of the NS neurons were large in the majority (70%) of the cases and included several areas of the body. A more marked activation was often obtained from stimuli applied to one part of the body, denoted as the preferential receptive field (PRF). In the other cases (30%), the excitatory receptive field was relatively small (SRF) and restricted to one part of the body (the tail, a paw, a hemiface, or the tongue). Both the PRF and SRF were more often located on the contralateral side. In addition, noxious stimuli applied outside the excitatory receptive field were found to strongly inhibit the responses of NS neurons. 6. All the NS neurons responded to intense transcutaneous electrical stimulation applied to the PRF or SRF with two peaks of activation.(ABSTRACT TRUNCATED AT 400 WORDS)


1995 ◽  
Vol 73 (2) ◽  
pp. 568-585 ◽  
Author(s):  
H. Bester ◽  
L. Menendez ◽  
J. M. Besson ◽  
J. F. Bernard

1. Parabrachiohypothalamic (PB-H) neurons (n = 71) were recorded with extracellular micropipettes in the parabrachial (PB) area and were antidromically driven from the ventromedial nucleus (VMH) or the retrochiasmatic area (RCh) of the hypothalamus, in the anesthetized rat. The spontaneous activity of these neurons was very low, (10th percentile < median frequency < 90th percentile were 0.01 < 0.2 < 7 Hz). The axons of these neurons exhibited a very slow conduction velocity in the range of 0.2-1.4 m/s, i.e., corresponding to thin unmyelinated fibers. 2. Most PB-H neurons (89%) were located in the mesencephalic division of the PB area (mPB) mainly in the superior lateral (mPBsl) and external lateral (mPBel) subnuclei. 3. These units were separated in three groups: 1) a group of nociceptive-specific (NS) neurons (49%) activated by mechanical and/or thermal (heat) cutaneous stimuli only in noxious range; 2) a group of inhibited neurons (7%), not activated by any of the mechanical or thermal cutaneous stimuli but inhibited, by at least one of these stimuli, which had to be in noxious range; and 3) a group of nonresponsive neurons (44%). 4. The NS neurons responded exclusively to mechanical (pinch or squeeze) and/or thermal (waterbath or waterjet > 44 degrees C) noxious stimuli with a rapid onset, a marked and sustained activation, and generally no afterdischarge. The magnitude of the responses was between 2 and 30 Hz with a mean value of 14.8 +/- 1.4 Hz (mean +/- SE, n = 49). These neurons exhibited a clear capacity to encode thermal stimuli in the noxious range: 1) the stimulus-response function was always positive and monotonic; 2) the slope of the mean curve increased up to a maximum (between 46 and 50 degrees C) then beyond the slope decreased; and 3) the mean threshold was 44.3 +/- 2.2 degrees C. 5. The excitatory receptive fields of the NS neurons were often large including all (22% of the population) or several (67% of the population) parts of the body. In the few remaining cases (11%) they were restricted to one part of the body. In addition, in several cases, noxious stimuli applied outside the excitatory receptive field were found to strongly inhibit the discharge of NS neurons. 6. Most NS neurons responded to intense transcutaneous electrical stimulation with two peaks of activation.(ABSTRACT TRUNCATED AT 400 WORDS)


1986 ◽  
Vol 56 (5) ◽  
pp. 1397-1410 ◽  
Author(s):  
S. L. Jones ◽  
G. F. Gebhart

A total of 51 dorsal horn units responsive to heat were isolated and their receptive fields characterized (i.e., response properties and adequate stimuli determined) in pentobarbital-anesthetized, paralyzed rats. In 39 of the 51 units, the descending inhibition of heat-evoked activity produced by focal electrical stimulation in the locus ceruleus/subceruleus (LC/SC) was examined. All units studied responded to mechanical stimulation, to electrical stimulation of the ipsilateral tibial nerve at intensities supramaximal to activate A-alpha, delta- and C-fibers, and to noxious heating (50 degrees C) of the footpad. The cutaneous receptive fields of all units were confined to the glabrous skin of the toes and footpad. All neurons examined were located in the dorsal horn of the spinal cord in laminae I-VI. Tracking experiments established that inhibition of heat-evoked dorsal horn unit activity could be reliably produced by focal electrical stimulation in both the contralateral and ipsilateral LC/SC. The inhibition produced by electrical stimulation in the LC/SC was intensity-, pulse duration-, and frequency-dependent. In six experiments, the efficacy of LC/SC stimulation-produced inhibition of heat-evoked activity was compared using two pulse durations (100 and 400 microseconds); greater inhibition of heat-evoked activity was produced at lower intensities of stimulation at the 400-microseconds pulse duration. In 10 experiments, the frequency of stimulation was varied (25-200 Hz); stimulation at a frequency of 100 Hz resulted in maximal inhibition of heat-evoked activity for stimulation sites both inside (n = 7) and outside (n = 3) the LC/SC. Inhibition of heat-evoked dorsal horn unit activity could be reliably produced by focal electrical stimulation in sites inside the LC/SC (n = 18). Significant descending inhibition of noxious heat-evoked spinal neuronal activity could also be produced by stimulation in pontine sites located outside the LC/SC, however, not as reliably. Systematic electrode tracks were made through the pons, using a searching stimulus of 100 microA, to locate sites medial, lateral, and ventral to the LC/SC from which significant descending inhibition could be produced. Stimulation in 156 sites outside the LC/SC at 100 microA produced inhibition of heat-evoked spinal unit activity to 50% of control or less in only 37 sites. Descending inhibition was characterized quantitatively from 14 of these 37 sites; the mean intensities of stimulation to inhibit heat-evoked activity to 50% of control were experimentally determined, and the mean thresholds of stimulation for inhibition and the mean recruitment indices were calculated.(ABSTRACT TRUNCATED AT 400 WORDS)


1988 ◽  
Vol 60 (3) ◽  
pp. 980-1009 ◽  
Author(s):  
L. Villanueva ◽  
D. Bouhassira ◽  
Z. Bing ◽  
D. Le Bars

1. In anesthetized rats recordings were made from neurons in the medulla caudal to the obex. In the medullary dorsal horn, typical trigeminal noxious specific, nonnoxious specific, and convergent neurons were found. In nucleus cuneatus, typical dorsal column units were recorded. In subnucleus reticularis dorsalis (SRD), recordings were made from neurons which exhibited convergence of nociceptive inputs from the entire body. In subnucleus reticularis ventralis (SRV) we recorded both from neurons with spontaneous activity that were either unaffected or inhibited by noxious stimuli applied to various parts of the body and from respiratory neurons. The present paper deals particularly with the nature of the stimuli that activated reticular neurons exhibiting nociceptive convergence. 2. Neurons with nociceptive convergence could be activated by mechanical, thermal, or chemical noxious stimuli applied to widespread areas of the body. By using percutaneous electrical stimulation, we found that they responded to the activation of peripheral fibers in the A delta- and C-range. Two neuronal subpopulations were defined according to the way in which SRD neurons responded to the electrical stimuli, namely: "neurons with total nociceptive convergence" (TNC) and "neurons with partial nociceptive convergence" (PNC). 3. The great majority (84%) of TNC neurons did not exhibit spontaneous activity and none of these neurons gave responses to heterosensory (flashes, whistle sounds) or proprioceptive stimuli. Most (88%) did not respond to any kind of innocuous cutaneous stimuli. By contrast, the entire population of TNC neurons responded to noxious mechanical, thermal, and visceroperitoneal stimuli. In the majority of cases (71%) long-lasting afterdischarges were observed following cessation of the application of the nociceptive stimulus. 4. All the TNC neurons responded to suprathreshold percutaneous electrical stimulation (2-ms duration) with two peaks of activation no matter which part of the body was stimulated. By stimulating two regions of the tail, 100 mm apart, we determined that the early and late peaks of activation were triggered by activities in peripheral fibers with mean conduction velocities of 10.8 +/- 0.5 and 0.74 +/- 0.05 (SE) m/s, respectively, i.e., A delta- and C-fibers. The mean thresholds for obtaining A delta-fiber components were found in the 0.4-0.7-mA range; the mean thresholds for obtaining C-fiber components were found in the 6-7.5- and 3-4-mA range for the face and the other parts of the body, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)


1992 ◽  
Vol 68 (2) ◽  
pp. 551-569 ◽  
Author(s):  
J. F. Bernard ◽  
G. F. Huang ◽  
J. M. Besson

1. Neurons (n = 177) were recorded with extracellular micropipettes in and around the nucleus centralis of the amygdala (Ce), in anesthetized rats. The spontaneous activity of these neurons was variable (0.25 less than 3 less than 35 Hz, n = 175; 10th percentile less than median less than 90th percentile). A majority (80%) of these neurons were excited or inhibited exclusively or preferentially by noxious stimuli. These units were separated into two groups: 1) a group of neurons excited by noxious stimuli (46% of the whole population) and 2) a group of neurons inhibited by noxious stimuli (34% of the whole population). 2. The receptive fields of both groups of neurons were very large: in about one-half the cases the neurons responded similarly from all parts of the body, and in the other cases the responses were greater when the stimuli were applied to a restricted part of the body. 3. Seventy-seven percent of the excited neurons had responses of relatively high magnitudes. In this group, most cells (75%) were exclusively driven by noxious stimuli; the others (25%) were preferentially activated by noxious stimuli. These neurons responded to mechanical (pinch or squeeze) and/or thermal (water bath or water jet greater than 44 degrees C) noxious stimuli with a marked and sustained activation. 4. Sixty percent of the inhibited neurons had a marked decrease of activity in response to noxious stimuli. In this group, most of them (81%) were exclusively inhibited by noxious stimuli, whereas the remainder (19%) were preferentially inhibited by noxious stimuli. These neurons responded to mechanical (pinch or squeeze) and/or thermal (water bath or waterjet greater than 44 degrees C) noxious stimuli with a suppression or a marked and sustained decrease in activity. 5. All of the nociceptive neurons responded to intense transcutaneous electrical stimulation with one or several components of activation or inhibition. According to their latencies, three types of components were distinguished: early, intermediate, and late components. We estimate that the early and the intermediate components would be triggered by the activity of peripheral fibers in the 6- to 20-m/s range and therefore could be in the A delta fibers range, whereas the late component would be triggered by fibers in the 0.5- to 1-m/s range and therefore could be in the C fibers range. 6. The neurons excited or inhibited by noxious stimuli were not homogeneously distributed in and around the Ce.(ABSTRACT TRUNCATED AT 400 WORDS)


1983 ◽  
Vol 50 (6) ◽  
pp. 1479-1496 ◽  
Author(s):  
D. R. Kenshalo ◽  
O. Isensee

Recordings were made from single SI cortical neurons in the anesthetized macaque monkey. Each isolated cortical neuron was tested for responses to a standard series of mechanical stimuli. The stimuli included brushing the skin, pressure, and pinch. The majority of cortical neurons responded with the greatest discharge frequency to brushing the receptive field, but neurons were found in areas 3b and 1 that responded maximally to pinching the receptive field. A total of 68 cortical nociceptive neurons were examined in 10 animals. Cortical neurons that responded maximally to pinching the skin were also tested for responses to graded noxious heat pulses (from 35 to 43, 45, 47, and 50 degrees C). If the neuron failed to respond or only responded to 50 degrees C, the receptive field was also heated to temperatures of 53 and 55 degrees C. Fifty-six of the total population of nociceptive neurons were tested for responses to the complete series of noxious heat pulses: 46 (80%) exhibited a progressive increase in the discharge frequency as a function of stimulus intensity, and the spontaneous activity of two (4%) was inhibited. One population of cortical nociceptive neurons possessed restricted, contralateral receptive fields. These cells encoded the intensity of noxious mechanical and thermal stimulation. Sensitization of primary afferent nociceptors was reflected in the responses of SI cortical nociceptive neurons when the ascending series of noxious thermal stimulation was repeated. The population of cortical nociceptive neurons with restricted receptive fields exhibited no adaptation in the response during noxious heat pulses of 47 and 50 degrees C. At higher temperatures the response often continued to increase during the stimulus. The other population of cortical nociceptive neurons was found to have restricted, low-threshold receptive fields on the contralateral hindlimb and, in addition, could be activated only by intense pinching or noxious thermal stimuli delivered on any portion of the body. The stimulus-response functions obtained from noxious thermal stimulation of the contralateral hindlimb were not different from cortical nociceptive neurons with small receptive fields. However, nociceptive neurons with large receptive fields exhibited a consistent adaptation during a noxious heat pulse of 47 and 50 degrees C. Based on the response characteristics of these two populations of cortical nociceptive neurons, we conclude that neurons with small receptive fields possess the ability to provide information about the localization, the intensity, and the temporal attributes of a noxious stimulus.4+.


1984 ◽  
Vol 51 (3) ◽  
pp. 467-480 ◽  
Author(s):  
W. D. Willis ◽  
K. D. Gerhart ◽  
W. S. Willcockson ◽  
R. P. Yezierski ◽  
T. K. Wilcox ◽  
...  

Recordings were made from 132 raphe- and reticulospinal tract neurons in the medial part of the lower brain stem in 32 anesthetized monkeys. Recording sites were in the nucleus raphe magnus, the rostral nucleus raphe obscurus, and the reticular formation adjacent to the raphe. The neurons were identified by antidromic activation from the upper lumbar spinal cord. Of the population sampled, 83 cells were activated antidromically from the left dorsal lateral funiculus (DLF), 32 from the right DLF, and 17 from both sides. The mean latency for antidromic activation was 8.2 +/- 7.1 ms, corresponding to a mean conduction velocity of 22.8 m/s. No conduction velocities characteristic of unmyelinated axons were observed. Collision tests indicated that raphe-spinal axons that bifurcated to descend in both DLFs branched within the spinal cord. The effects of stimulation in the periaqueductal gray (PAG) or adjacent midbrain reticular formation were tested on 102 spinally projecting neurons in the medial medulla. Of these, 60 cells were excited, 9 cells were inhibited, 8 showed mixed excitation and inhibition, and 25 cells were unaffected. The mean latency for excitation was 11.6 ms and for inhibition, 17.8 ms. Threshold for excitation of raphe- and reticulospinal neurons ranged from 50 to 400 microA. Raphe- and reticulospinal tract cells could often (31/46 cells tested) be excited following stimulation in the ventral posterior lateral nucleus of the thalamus. The mean latency of excitation was 35.6 ms (range, 6-112 ms). Receptive fields could be demonstrated for 80 raphe- and reticulospinal cells, while 48 neurons possessed no demonstrable cutaneous receptive field. Most cells had large excitatory receptive fields, often encompassing the surface of the entire body and face. Some neurons had complex excitatory and inhibitory receptive fields, whereas other cells had large inhibitory receptive fields over much of the surface of the body and face. For most cells (52/55) with excitatory receptive fields, the only effective stimuli were noxious mechanical or noxious heat stimuli. Nonnoxious mechanical stimuli, such as brushing the skin, were capable of activating only a few (3/55) raphe- and reticulospinal neurons, and these were more effectively excited by noxious stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)


2005 ◽  
Vol 94 (1) ◽  
pp. 219-225 ◽  
Author(s):  
S. K. Sauer ◽  
C. Weidner ◽  
R. W. Carr ◽  
B. Averbeck ◽  
U. Nesnidal ◽  
...  

Threshold tracking of individual polymodal C- and Aδ-fiber terminals was used to assess membrane potential changes induced by de- or hyperpolarizing stimuli in the isolated rat skin–nerve preparation. Constant current pulses were delivered (1 Hz) through a tungsten microelectrode inserted in the receptive field, and the current amplitude was controlled by feedback with a laboratory computer programmed to serially determine the electrical threshold using the method of limits. During threshold tracking, the receptive fields of the fibers were heated (32–46°C in 210 s) or superfused with modified synthetic interstitial fluid containing either 0, 20, 40, 50, or 60 mM [K+], phosphate buffer to pH 5.2 or 6.1, or bradykinin (BK, 10−8–10-5 M). High [K+]e decreased the current threshold for activation by 6–14% over 120 s, whereas K+-free superfusion augmented the threshold by >5%, and after some delay, also induced ongoing discharge in 60% of units. pH 6.1 and 5.2 caused an increase in threshold of 6 and 18%, respectively, and 30% of the fibers were excited by low pH, although the change in threshold of pH responsive and unresponsive fibers did not differ significantly, suggesting a general excitability decrease induced by protons. Heat stimulation increased the mean threshold and conduction velocity of the fibers tested and resulted in activity in 78% of units. Additionally, for these units, activation was preceded by a significant decrease in threshold compared with the tracked thresholds of fibers unresponsive to heat. Bradykinin also led to a significant threshold decrease before activation. In conclusion, the technique of threshold tracking proved suitable to assess changes in excitability resulting from receptor currents evoked by noxious heat and bradykinin in the terminal arborization of cutaneous nociceptors.


1990 ◽  
Vol 64 (6) ◽  
pp. 1712-1723 ◽  
Author(s):  
D. Bouhassira ◽  
Z. Bing ◽  
D. Le Bars

1. Diffuse noxious inhibitory controls (DNIC) were compared in control sham-operated rats and in rats with lesions of mesencephalic structures involved in the modulation of pain, namely the periaqueductal gray (PAG), cuneiformis nucleus (CNF), and parabrachial nucleus (PB). 2. Lesions were induced by ibotenic acid: 4 micrograms (0.2 microliter) injected bilaterally in the PAG or the CNF-PB area or 10 micrograms (0.5 microliter) injected unilaterally in the CNF or PB. Control animals were microinjected with the vehicle (artificial CSF) alone. Histological controls were performed at the end of each electrophysiological experiment. Only the animals in which the target structure (PAG, CNF, or PB) was completely destroyed in its entire rostrocaudal length were selected. With the exception of the cell bodies of the trigeminal mesencephalic nucleus, all neurons were destroyed in these regions. 3. At least 1 wk after the microinjection procedure, recordings were made from convergent neurons in both the right and left trigeminal nucleus caudalis. These neurons were activated by both noxious and nonnoxious stimuli applied to their excitatory receptive fields and gave responses due to activation of both A- and C-fibers after percutaneous electrical stimulation of their receptive fields. These types of response were inhibited by applying noxious conditioning stimuli to heterotopic areas of the body, namely immersing a paw in a 50 degrees C water bath. A virtually total block of the responses was observed during the application of the noxious conditioning stimulus, and this was followed by long-lasting poststimulus effects. 4. The general properties of neurons (sizes of receptive fields, spontaneous activity, thresholds to obtain C-fiber-evoked responses, responses to C-fiber activation) were all found to be similar in the control and the lesioned animals. The percentage inhibition of the C-fiber-evoked responses of the trigeminal convergent neurons elicited by the noxious conditioning stimuli were found to not be significantly different in any group of animals; in all the animals, inhibitions exceeded 85% during the immersion of either paw and were followed by long-lasting poststimulus effects. 5. We conclude that the PAG, CNF, and PB, three structures that are putatively involved in the modulation of pain, do not participate directly in the supraspinal part of the loop subserving DNIC. The involvement of other structure(s) and a possible indirect modulation of DNIC are discussed. It is also concluded that the PAG, CNF, and PB do not participate directly in the tonic descending inhibitory controls, which are presumed to modulate the activity of convergent neurons.


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