Nociceptive responses of neurons in medial thalamus and their relationship to spinothalamic pathways

1978 ◽  
Vol 41 (6) ◽  
pp. 1592-1613 ◽  
Author(s):  
W. K. Dong ◽  
H. Ryu ◽  
I. H. Wagman

1. An extracellular study of the cat medial thalamus has revealed four types of somatosensory neurons. These were located primarily in the n. parafascicularis, n. subparafascicularis, and n. centralis lateralis; none were found in the n. centrum medianum. There was no functional segregation of neurons within each nucleus or between nuclei. Each type of neuron had large and often bilateral receptive areas. No somatotopic organization of neurons was found within the medial thalamus. 2. Noxious (N) and noxious-tap (NT) neurons comprising 72% of the sample (78 of 109 total) were considered to be nociceptive. N cells responded exclusively to noxious mechanical stimulation of skin, muscle fascia, tendons, and joints, and to direct stimulation of A-delta- and C-fiber groups in cutaneous, articular, and muscle nerves. NT cells responded to noxious and tap stimulation in a differential manner and to stimulation of the entire spectrum of A- and C-fibers. N and NT cells accurately signaled the duration of noxious mechanical stimulation. Their nociceptive responses were also graded as a function of both noxious stimulus intensity and the number of activated A-delta- and C-fibers. Stimulation of A- and C-fibers evoked, respectively, an inital burst and a late burst of discharges. A brief period of inhibition intervened between the initial and late bursts of NT cells. Prolonged afterdischarge was often observed following noxious natural stimulation or stimulation of A-delta- and C-fibers. The phenomenon of discharge "windup" was observed during iterative stimulation of C-fibers. 3. Tap (T) neurons (10%) responded only to brisk but innocuous taps applied to skin or underlying tissue. These cells were driven only by activation of A-alpha- and A-beta-fibers. The response to such stimulation was seen as an initial burst of discharges followed by an inhibitory period. 4. Inhibited (I) neurons (18%) had resting discharges that were inhibited by noxious stimuli and stimulation of A-beta- and C-fiber groups. 5. The results obtained from monitoring the peripherally evoked responses of nociceptive N and NT neurons before and after selective lesions of the spinal cord strongly suggested that the spinothalamic tracts were the only spinal projections mediating A- and C-fiber input to these cells. Each spinothalamic tract apparently carried information originating from both sides of the body.

1985 ◽  
Vol 54 (1) ◽  
pp. 73-89 ◽  
Author(s):  
W. S. Ammons ◽  
M. N. Girardot ◽  
R. D. Foreman

Spinothalamic tract neurons projecting to medial thalamus (M-STT cells), ventral posterior lateral nucleus (VPL) of the thalamus (L-STT cells), or both thalamic regions (LM-STT cells) were studied in 19 monkeys anesthetized with alpha-chloralose. Twenty-seven M-STT cells were antidromically activated from nucleus centralis lateralis, nucleus centrum medianum, or the medial dorsal nucleus. Stimulation of VPL elicited antidromic responses from 22 cells and 13 cells were activated from both VPL and medial thalamus. Antidromic conduction velocities of M-STT cells were significantly slower than those of L-STT or LM-STT cells. M-STT cells were located in laminae I, IV, V, and VII with greater numbers found in the deepest laminae. L-STT cells were located mostly in lamina IV, whereas most LM-STT cells were found in lamina V. Twenty-four of 27 M-STT cells, all L-STT cells, and all LM-STT cells received input from both cardiopulmonary sympathetic and somatic afferent fibers. WDR cells were most common among the L-STT and LM-STT groups, whereas HT cells were the most common class in the M-STT cell group. Excitatory receptive fields of M-STT cells were large, and often bilateral. Receptive fields of L-STT cells were simple and never bilateral. Receptive fields of LM-STT cells could be similar to M-STT or L-STT cells. Thirty-three percent of the M-STT cells, 37% of the L-STT cells, and 62% of the LM-STT cells had inhibitory receptive fields. Inhibition was elicited most often by a noxious pinch of the hindlimbs. Sixteen of 23 (70%) M-STT cells received C-fiber cardiopulmonary sympathetic input in addition to A-delta-fiber input. The other 7 cells received only A-delta-fiber input. Only 45% of the L-STT cells and 38% of the LM-STT cells received both A-delta- and C-fiber inputs. The maximum number of spikes elicited by A-delta-input was related to segmental locations for L-STT cells with greatest responses in T2 and lesser responses in more caudal segments; however, no such trend was apparent for M-STT cells or for responses to C-fiber input for either group. Electrical stimulation of the left thoracic vagus nerve inhibited 7 of 18 M-STT cells, 10 of 16 L-STT cells, and 6 of 12 LM-STT cells. These results are the first description of visceral input to cells projecting to medial thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)


1990 ◽  
Vol 63 (5) ◽  
pp. 1118-1127 ◽  
Author(s):  
L. Villanueva ◽  
K. D. Cliffer ◽  
L. S. Sorkin ◽  
D. Le Bars ◽  
W. D. Willis

1. Recordings were made in anesthetized monkeys from neurons in the medullary reticular formation (MRF) caudal to the obex. Responses of 19 MRF neurons to mechanical, thermal, and/or electrical stimulation were examined. MRF neurons exhibited convergence of nociceptive cutaneous inputs from widespread areas of the body and face. 2. MRF neurons exhibited low levels of background activity. Background activity increased after periods of intense cutaneous mechanical or thermal stimulation. Nearly all MRF neurons tested failed to respond to heterosensory stimuli (flashes, whistle sounds), and none responded to joint movements. 3. MRF neurons were excited by and encoded the intensity of noxious mechanical stimulation. Responses to stimuli on contralateral limbs were greater than those to stimuli on ipsilateral limbs. Responses were greater to stimuli on the forelimbs than to stimuli on the hindlimbs. 4. MRF neurons responded to noxious thermal stimulation (51 degrees C) of widespread areas of the body. Mean responses from stimulation at different locations were generally parallel to those for noxious mechanical stimulation. Responses increased with intensity of noxious thermal stimulation (45-50 degrees C). 5. MRF neurons responded with one or two peaks of activation to percutaneous electrical stimulation applied to the limbs, the face, or the tail. The differences in latency of responses to stimulating two locations along the tail suggested that activity was elicited by activation of peripheral fibers with a mean conduction velocity in the A delta range. Stimulation of the contralateral hindlimb elicited greater responses, with lower thresholds and shorter latencies, than did stimulation of the ipsilateral hindlimb. 6. Electrophysiological properties of monkey MRF neurons resembled those of neurons in the medullary subnucleus reticularis dorsalis (SRD) in the rat. Neurons in the caudal medullary reticular formation could play a role in processing nociceptive information. Convergence of nociceptive cutaneous input from widespread areas of the body suggests that MRF neurons may contribute to autonomic, affective, attentional, and/or sensory-motor processes related to pain.


2002 ◽  
Vol 87 (4) ◽  
pp. 1889-1901 ◽  
Author(s):  
D. Andrew ◽  
A. D. Craig

Noxious mechanical stimuli that are maintained for minutes produce a continuous sensation of pain in humans that augments during the stimulus. It has recently been shown with systematic force-controlled stimuli that, while all mechanically responsive nociceptors adapt to these stimuli, the basis for such pain can be ascribed to A-fiber rather than C-fiber nociceptors, based on distinctions in their respective response profiles and stimulus-response functions. The present experiments investigated whether similar distinctions could be made in subsets of nociceptive lamina I spinothalamic tract (STT) neurons using similar maintained stimuli. Twenty-eight lamina I STT neurons in the lumbosacral dorsal horn of barbiturate-anesthetized cats were tested with noxious mechanical stimuli applied with a probe of 0.1 mm2 contact area at forces of 25, 50, and 100 g for 2 min. The neurons were classified as nociceptive-specific (NS, n = 14) or polymodal nociceptive (HPC, n = 14) based on their responses to quantitative thermal stimuli. The NS neurons had greater responses and showed less adaptation than the HPC neurons in response to these stimuli, and they encoded stimulus intensity better. Comparison of the normalized response profiles of all 28 nociceptive lamina I STT neurons, independent of cell classification, revealed 2 subgroups that differed significantly: “Maintained” cells with responses that remained above 50% of the initial peak rate during stimulation and “Adapting” cells with responses that quickly declined to <50%. The Maintained neurons encoded the intensity of the mechanical stimuli better than the Adapting neurons, based on ratiometric functions. A k-means cluster analysis of all 28 cells distinguished the identical two subgroups. These categories corresponded closely to the NS and HPC categories: Maintained cells were mostly NS neurons (10 NS, 3 HPC), and Adapting cells were mostly HPC neurons (4 NS, 11 HPC). Thus the present data are consistent with the distinctions between A-fiber and C-fiber nociceptors observed previously, because A-fiber nociceptors are the predominant input to NS lamina I STT neurons and C-fiber nociceptors are the predominant input to HPC neurons. These findings support the view that NS, but perhaps not HPC, lamina I STT neurons have a role in the pain caused by maintained mechanical stimuli and contribute to the sensations of “first” pain and “sharpness.” Nonetheless, none of the units studied showed increasing responses during the stimuli, suggesting a role for other ascending neurons or forebrain integration in the augmenting pain produced by maintained mechanical stimulation.


1985 ◽  
Vol 54 (3) ◽  
pp. 491-501 ◽  
Author(s):  
V. K. Shea ◽  
E. R. Perl

The cutaneous receptive properties of unmyelinated (C) fibers of the rabbit's great auricular nerve were determined by single-unit recordings. The majority of C-fiber units could be excited by cutaneous stimulation, and such sensory units fell into three major categories on the basis of responses to mechanical and thermal stimulation of their cutaneous receptive fields: low-threshold mechanoreceptors, nociceptors, or specific thermoreceptors. The majority of afferent elements were nociceptive, and all nociceptors responded to strong mechanical stimulation. Three types of nociceptors could be distinguished by their responses to thermal stimuli. Polymodal nociceptors responded to heat with thresholds of 40-55 degrees C and typically displayed enhanced responses or sensitization after noxious heating of their receptive fields. High-threshold mechanoreceptors failed to respond promptly to heat before noxious cutaneous stimulation which, however, elicited subsequent back-ground activity or sensitivity to heat. A third type of nociceptor responded to cold but not to heat. Low-threshold mechanoreceptors were identified by their brisk responses to very gentle, slowly moving mechanical stimulation of their receptive fields, and were readily distinguished from any element classified as nociceptive by their lower mechanical thresholds. Rapid innocuous warming or cooling excited some of the low-threshold mechanoreceptors. Specific thermoreceptors, both warming and cooling types, were rare, insensitive to mechanical stimulation, and responded to very slight changes in temperature. In contrast to the sensitization to heat, which was characteristic of most nociceptors, specific warming receptors displayed depressed thermal responses after noxious heating of their receptive fields. These results provide further evidence of the similarity of C-fiber receptors innervating hairy skin of different species. Some differences from past reports and additional features are described.


1993 ◽  
Vol 69 (6) ◽  
pp. 1890-1903 ◽  
Author(s):  
E. H. Chudler ◽  
K. Sugiyama ◽  
W. K. Dong

1. Extracellular recordings were made from neurons in the neostriatum (caudate nucleus-putamen, CPu) and globus pallidus (GP) of anesthetized rats. Few cells (3%) were classified as low-threshold-mechanoreceptive (LTM) neurons. The majority (97%) of somatosensory CPu and GP neurons responded differentially or exclusively to noxious mechanical stimulation of the skin. Nociceptive neurons were classified into the following three groups on the basis of their response properties to noxious mechanical stimulation: wide-dynamic-range (WDR) neurons (21%); nociceptive-specific (NS) neurons (67%); and inhibited (INH) neurons (13%). 2. No differences in the response properties or in the proportions of WDR, NS, and INH neurons were found in the CPu compared with the GP. Nociceptive neurons were located most often along the CPu-GP border. Additionally, neurons of similar functional classification were often clustered within 200-400 microns of each other along a single microelectrode track. 3. The receptive fields of nociceptive CPu and GP neurons were often large and bilateral; some receptive fields encompassed the entire body. The trigeminal region, especially the perioral area, was included in the receptive fields of nociceptive neurons more often (62 of 63 cells) than any other part of the body. However, no preference for any particular division of the trigeminal nerve was observed in the receptive fields. Some neurons had receptive fields that were discontinuous. 4. Noxious pinching of the skin significantly increased the spontaneous neuronal discharge of WDR and NS neurons by an average of 482 and 221%, respectively. There were no significant differences between the discharge adaptation rates of WDR and NS neurons. Afterdischarge activity was observed in some WDR and NS neurons. INH neurons decreased their resting activity levels by an average of 43% after a noxious pinch. 5. The von Frey stimulus threshold of WDR neurons (11.0 g/mm2) was significantly lower than that of NS neurons (33.6 g/mm2) and INH neurons (32.6 g/mm2). Mean stimulus thresholds of WDR, NS, and INH neurons determined by using calibrated forceps were 1.6, 4.8, and 2.2 g/mm2, respectively. 6. Individual stimulus-response functions of nociceptive neurons were best fit by a negatively accelerating (logarithmic) curves. However, WDR neurons had significantly steeper slopes than NS neurons. 7. The results demonstrate that a large proportion of somatosensory neurons within the neostriatum and globus pallidus (especially along the CPu-GP border) receive nociceptive information. These data are discussed in relation to several putative afferent nociceptive pathways projecting to the CPu and GP.(ABSTRACT TRUNCATED AT 400 WORDS)


1997 ◽  
Vol 273 (6) ◽  
pp. H2726-H2737 ◽  
Author(s):  
Liang-Wu Fu ◽  
Hui-Lin Pan ◽  
John C. Longhurst

Abdominal ischemia stimulates sympathetic visceral afferents to reflexly activate the cardiovascular system. We have shown previously that topical application of histamine (HA) to the gastric wall causes reflex cardiovascular responses and have documented increased histamine concentrations in intestinal lymph and portal venous plasma during brief abdominal ischemia. In the present study, we hypothesized that histamine produced during ischemia activates ischemically sensitive C-fiber afferents by stimulation of H1 receptors. Nerve activity of single-unit abdominal visceral C-fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats. Injection of histamine (25 μg/kg ia) significantly increased activity of nine ischemically sensitive C fibers from 0.09 ± 0.06 to 1.11 ± 0.20 imp/s. An H1-receptor agonist, 2-(3-chlorophenyl)histamine (250 μg/kg ia), also increased activity of these afferents from 0.11 ± 0.04 to 0.64 ± 0.18 imp/s ( P < 0.05). Furthermore, an H1-receptor antagonist (pyrilamine, 0.2 mg/kg iv) significantly attenuated the increased activity in 11 other C fibers from 0.91 ± 0.16 to 0.35 ± 0.06 imp/s (ischemia vs. pyrilamine + ischemia) and eliminated the response of 9 separate ischemically sensitive afferents to histamine. Conversely, both the H2-receptor agonist dimaprit (500 μg/kg ia) and the H3-receptor agonist ( R)-α-methylhistamine (250 μg/kg ia) did not significantly alter the activity of these nine afferents. In nine separate cats treated with indomethacin (5 mg/kg iv), pyrilamine (0.2 mg/kg iv) further significantly attenuated the increased activity in seven of nine C fibers during ischemia, and indomethacin (5 mg/kg iv) attenuated the response of eight other afferents to histamine. These data suggest that during mesenteric ischemia endogenous histamine contributes to the activation of afferents through direct stimulation of histamine H1 receptors and that histamine’s stimulating effect on these afferents is dependent partially on production of prostaglandins.


1989 ◽  
Vol 61 (2) ◽  
pp. 391-402 ◽  
Author(s):  
L. Villanueva ◽  
Z. Bing ◽  
D. Bouhassira ◽  
D. Le Bars

1. In anesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurons that exhibited convergence of nociceptive inputs from the entire body. Neurons with total nociceptive convergence (TNC) responded to suprathreshold percutaneous electrical stimuli (2-ms duration) with an early and a late peak due to activation of A delta- and C-fibers, respectively, no matter which part of the body was stimulated. Neurons with partial nociceptive convergence (PNC) responded to the same stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurons to the application of graded intensities of electrical, thermal, and mechanical stimuli were analyzed. 2. All TNC neurons and 85% of PNC neurons responded to A delta- and C-fiber activation following percutaneous electrical stimulation of the contralateral hindpaw. With regard to A delta-fiber-evoked responses, a linear relationship between the logarithm of the applied current and the magnitude of the responses was found within the 0.25- to 6.0-mA and 0.5- to 24-mA ranges for TNC and PNC neurons, respectively; however, these curves were essentially similar. With regard to C-fiber-evoked responses, such a linear relationship was found within the 1.5- to 6.0-mA range for both types of SRD neurons, although the TNC neurons presented larger C-fiber-evoked responses than did the PNC neurons. 3. TNC and PNC neurons linearly increased their discharges during the application of noxious thermal stimuli to the contralateral hindpaw within the range 44-52 degrees C; the mean responses evoked by noxious heat from TNC neurons were of higher magnitude than those from PNC neurons. The majority of SRD neurons presented long-lasting afterdischarges, especially with the highest temperature employed (52 degrees C). 4. TNC neurons monotonically increased their discharges during graded mechanical or thermal stimulation of the tail. When mechanical stimuli were applied, a linear relationship was found between the logarithm of the strength of the mechanical stimulus and the neuronal discharges, in the 5.3- to 7.4-N/cm2 range. With thermal stimulation, TNC neurons linearly increased their discharges in the 44-52 degrees C range. When increasing amounts of the tail were immersed in a 50 degrees C waterbath, TNC neurons increased their discharges within a restricted range of tail surface areas (0.9-5.7 cm2); further increases in the stimulated surface size were not followed by increases in firing rate.(ABSTRACT TRUNCATED AT 400 WORDS)


In the study of the phenomena of anaphylaxis there are certain points on which some measure of agreement seems to have been attained. In the case of anaphylaxis to soluble proteins, with which alone we are directly concerned in this paper, the majority of investigators probably accept the view that the condition is due to the formation of an antibody of the precipitin type. Concerning the method, however, by which the presence of this antibody causes the specific sensitiveness, the means by which its interaction with the antibody produces the anaphylactic shock, there is a wide divergence of conception. Two main currents of speculation can be discerned. One view, historically rather the earlier, and first put forward by Besredka (1) attributes the anaphylactic condition to the location of the antibody in the body cells. There is not complete unanimity among adherents of this view as to the nature of the antibody concerned, or as to the class of cells containing it which are primarily affected in the anaphylactic shock. Besredka (2) himself has apparently not accepted the identification of the anaphylactic antibody with a precipitin, but regards it as belonging to a special class (sensibilisine). He also regards the cells of the central nervous system as those primarily involved in the anaphylactic shock in the guinea-pig. Others, including one of us (3), have found no adequate reason for rejecting the strong evidence in favour of the precipitin nature of the anaphylactic antibody, produced by Doerr and Russ (4), Weil (5), and others, and have accepted and confirmed the description of the rapid anaphylactic death in the guinea-pig as due to a direct stimulation of the plain-muscle fibres surrounding the bronchioles, causing valve-like obstruction of the lumen, and leading to asphyxia, with the characteristic fixed distension of the lungs, as first described by Auer and Lewis (6), and almost simultaneously by Biedl and Kraus (7). But the fundamental conception of anaphylaxis as due to cellular location of an antibody, and of the reaction as due to the union of antigen and antibody taking place in the protoplasm, is common to a number of workers who thus differ on details.


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