Spinothalamic and spinohypothalamic tract neurons in the sacral spinal cord of rats. II. Responses to cutaneous and visceral stimuli

1996 ◽  
Vol 75 (6) ◽  
pp. 2606-2628 ◽  
Author(s):  
J. T. Katter ◽  
R. J. Dado ◽  
E. Kostarczyk ◽  
G. J. Giesler

1. A goal of this study was to determine whether neurons in the sacral spinal cord that project to the diencephalon are involved in the processing and transmission of sensory information that arises in the perineum and pelvis. Therefore, 58 neurons in segments L6-S2 were activated antidromically with currents < or = 30 microA from points in the contralateral diencephalon in rats that were anesthetized with urethan. 2. Responses to mechanical stimuli applied to the cutaneous receptive fields of these neurons were used to classify them as low-threshold (LT), wide dynamic range (WDR) or high-threshold (HT) neurons. Twenty-two neurons (38%) responded preferentially to brushing (LT neurons). Eighteen neurons (31%) responded to brushing but responded with higher firing frequencies to noxious mechanical stimuli (WDR neurons). Eighteen neurons (31%) responded only to noxious intensities of mechanical stimulation (HT neurons). LT neurons were recorded predominantly in nucleus proprius of the dorsal horn. Nociceptive neurons (WDR and HT) were recorded throughout the dorsal horn. 3. Cutaneous receptive fields were mapped for 56 neurons. Forty-five (80%) had receptive fields that included at least two of the following regions ipsilaterally: the rump, perineum, or tail. Eleven neurons (20%) had receptive fields that were restricted to one of these areas or to the ipsilateral hind limb. Thirty-eight neurons (68%) had cutaneous receptive fields that also included regions of the contralateral tail or perineum. On the perineum, receptive fields usually encompassed perianal and perivaginal areas including the clitoral sheath. There were no statistically significant differences in the locations or sizes of receptive fields for LT neurons compared with nociceptive (WDR and HT) neurons. 4. Thirty-seven LT, WDR, and HT neurons were tested for their responsiveness to heat stimuli. Five (14%) responded to increasing intensities of heat with graded increases in their firing frequencies. Thirty-two LT, WDR, and HT neurons also were tested with cold stimuli. None responded with graded increases in their firing frequencies to increasingly colder stimuli. There were no statistically significant differences among the responses of LT, WDR, and HT neurons to either heat or cold stimuli. 5. Forty LT, WDR, and HT neurons were tested for their responsiveness to visceral stimuli by distending a balloon placed into the rectum and colon with a series of increasing pressures. Seventeen (43%) exhibited graded increases in their firing frequencies in response to increasing pressures of colorectal distention (CrD). None of the responsive neurons responded reproducibly to CrD at an intensity of 20 mmHg, and all responded at intensities of > or = 80 mmHg. More than 90% responded abruptly at stimulus onset, responded continuously throughout the stimulus period, and stopped responding immediately after termination of the stimulus. 6. Thirty-one neurons were tested for their responsiveness to distention of a balloon placed inside the vagina. Eleven (35%) exhibited graded increases in their firing frequencies in response to increasing pressures of vaginal distention (VaD). The thresholds and temporal profiles of the responses to VaD were similar to those for CrD. Twenty-nine neurons were tested with both CrD and VaD. Thirteen (45%) were excited by both stimuli, four (14%) responded to CrD but not VaD, and one (3%) was excited by VaD but not CrD. Neurons excited by CrD, VaD, or both were recorded throughout the dorsal horn. 7. As a population, WDR neurons, but not LT or HT neurons, encoded increasing pressures of CrD and VaD with graded increases in their firing frequencies. The responses of WDR neurons to CrD differed significantly from those of either LT or HT neurons. Regression analyses of the stimulus-response functions of responsive WDR neurons to CrD and VaD were described by power functions with exponents of 1.6 and 2.4, respectively.(ABSTRACT TRUNCATED)

2005 ◽  
Vol 93 (2) ◽  
pp. 989-997 ◽  
Author(s):  
Lisa M. Johanek ◽  
Donald A. Simone

Low doses of cannabinoids applied intrathecally attenuate capsaicin-evoked heat and mechanical hyperalgesia via CB1 receptors. Although cannabinoids produce antinociception, in part, by attenuating responses of nociceptive neurons in the spinal cord, few studies have examined the effect of cannabinoids on sensitization of spinal neurons. We therefore investigated whether a cannabinoid receptor agonist, CP 55,940, attenuated excitation and sensitization of spinal nociceptive neurons produced by intraplantar injection of 0.1% capsaicin (10 μl). In rats, wide-dynamic-range (WDR) and high-threshold (HT) neurons were classified according to responses evoked by mechanical stimuli of varying intensity. CP 55,940 (10 μg in 50 μl) or vehicle was applied directly to the spinal cord and responses to mechanical (von Frey monofilament) and heat stimuli were recorded 10 min after drug treatment. CP 55,940 alone did not alter responses to mechanical stimuli; however the enhanced responses to mechanical stimuli after injection of capsaicin into the receptive field were dose dependently attenuated in both HT and WDR neurons. Vehicle-treated neurons increased their response to 300.6 ± 52.1% of baseline after capsaicin, whereas CP 55,940-treated neurons responded at 153.0 ± 27.1% of baseline. The effects of CP 55,940 on sensitization to heat were less pronounced; however, CP 55,940 attenuated the capsaicin-evoked decrease in heat threshold in HT neurons. The attenuation by CP 55,940 of sensitization to mechanical stimuli was blocked by pretreatment of the spinal cord with the CB1 receptor antagonist, SR141716A. These studies demonstrate that cannabinoid application to the spinal cord prevents central sensitization.


1994 ◽  
Vol 71 (3) ◽  
pp. 981-1002 ◽  
Author(s):  
R. J. Dado ◽  
J. T. Katter ◽  
G. J. Giesler

1. The goal of this study was to gather data that would increase our understanding of nociceptive processing by spinothalamic tract (STT) neurons that receive inputs from the hand and arm. Fifty neurons in the cervical enlargement of urethan-anesthetized rats were antidromically activated from the contralateral posterior thalamus. A stimulating electrode was moved systematically within an anterior-posterior plane in the thalamus until a point was located where the smallest amount of current antidromically activated the neuron. The antidromic thresholds at each of these lowest threshold points was < or = 30 microA; the mean antidromic threshold was 15.4 +/- 1.0 (SE) microA. Lowest threshold points were found primarily in the posterior thalamic group (Po), zona incerta, and in or near the supraoptic decussation. 2. The recording sites of 47 neurons were marked and recovered. Recording sites were located in the superficial dorsal horn (SDH, n = 15), deep dorsal horn (DDH, n = 31), and ventral horn (n = 1). Recording sites were located across the mediolateral extent of the SDH. Within the DDH, recording sites were concentrated laterally in nucleus proprius and dorsally in the lateral reticulated area. The locations of the recording points confirm previous anatomic descriptions of STT neurons in the cervical enlargement. 3. Cutaneous excitatory receptive fields were restricted to the ipsilateral forepaw or forelimb in 67% (10/15) of the neurons recorded in the SDH and 42% (13/31) of the neurons recorded in the DDH. Neurons having larger, more complex receptive fields were also commonly encountered. Thirty-three percent (5/15) of the neurons recorded in the SDH and 58% (18/31) recorded in the DDH had receptive fields that were often discontinuous and included areas of the ipsilateral shoulder, thorax, and head, including the face. 4. Innocuous and noxious mechanical stimuli were applied to the receptive field of each neuron. Fifty percent (25/50) responded to innocuous mechanical stimuli but responded at higher frequencies to noxious stimuli (wide dynamic range, WDR). Forty-four percent (22/50) responded only to noxious stimuli (high threshold, HT). Six percent (3/50) responded preferentially to innocuous stimuli (low threshold, LT). WDR and HT neurons were recorded in both the SDH and DDH, including nucleus proprius, an area not typically associated with nociceptive transmission at other levels of the cord. Sixty percent (9/15) of the units recorded in the SDH were classified as WDR neurons; the other 40% (6/15) were classified HT. Forty-eight percent (15/31) of the units recorded in the DDH were classified as WDR neurons and 42% (13/31) as HT.(ABSTRACT TRUNCATED AT 400 WORDS)


2003 ◽  
Vol 90 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Yuan Bo Peng ◽  
Qing Dong Ling ◽  
M. A. Ruda ◽  
Daniel R. Kenshalo

Neonatal peripheral inflammation has been shown to produce profound anatomical changes in the dorsal horn of adult rats. In this study, we explored whether parallel physiological changes exist. Neonatal rats were injected with complete Freund's adjuvant (CFA) into the left hind paw. At 8–10 wk of age, single dorsal horn neurons were recorded in response to graded intensities of mechanical stimuli delivered to the receptive field. In addition, cord dorsum potentials, produced by electrical stimuli delivered to the left sciatic nerve at 2.5× threshold, were recorded bilaterally from L2 to S3. There were significant increases in background activity and responses to brush and pinch in neonatal rats that were treated with CFA, as compared with control rats. Further analysis showed similar significant changes when dorsal horn neurons were categorized into wide dynamic range (WDR), high-threshold (HT), and low-threshold (LT) groups. The receptive field was significantly larger in neonatally treated rats as compared with control rats. Additionally, there was a significant increase in the response to a 49°C heat stimulus in neonatally treated rats as compared with control rats. There was also a trend for the amplitudes of N1, N2, and P waves of the cord dorsum potential to increase and latencies to decrease in neonatally treated rats, but no significant differences were detected between different levels of the spinal cord (L2 to S3). These data further support the notion that anatomical and physiological plasticity changes occurred in the spinal cord following early neonatal CFA treatment.


1989 ◽  
Vol 62 (2) ◽  
pp. 437-449 ◽  
Author(s):  
W. Maixner ◽  
R. Dubner ◽  
D. R. Kenshalo ◽  
M. C. Bushnell ◽  
J. L. Oliveras

1. We examined the activity of thermally sensitive trigeminothalamic neurons and nonprojection neurons in the medullary dorsal horn (trigeminal nucleus caudalis) in three monkeys performing thermal and visual detection tasks. 2. An examination of neuronal stimulus-response functions, obtained during thermal-detection tasks in which noxious heat stimuli were applied to the face, indicated that wide-dynamic-range neurons (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) could be subclassified based on the slope values of linear regression lines. WDR1 neurons exhibited significantly greater sensitivity to noxious heat stimulation than WDR2 neurons or nociceptive-specific neurons (NS, responsive only to noxious stimuli). 3. In one behavioral task, the monkeys detected 1.0 degrees C increases in noxious heat from preceding noxious heat stimuli ranging from 44 to 48 degrees C. WDR1, WDR2, and NS neurons increased their discharge frequency as a function of the intensity of the first noxious heat temperature (T1) as well as the final temperature (T2). The responses of WDR1 neurons were greater than those produced by WDR2 or NS neurons across all the temperatures examined. The order of stimulus presentation affected the responses of WDR1 neurons to 1.0 degrees C increases in the noxious heat range but not those of WDR2 or NS neurons. 4. In a second behavioral task, the monkeys detected small increases in noxious heat (0.2-0.8 degrees C) from a first temperature of 46 degrees C. Although the responses of all three classes of neurons were monotonically related to stimulus intensity, WDR1 neurons exhibited greater sensitivity to small temperature increases than either WDR2 or NS neurons. 5. Subpopulations of all three classes of neurons exhibited responses that were independent of thermal stimulus parameters or sensory modality and that only occurred during the behavioral task. These task-related responses were time-locked to specific behavioral events associated with trial initiation and trial continuation. 6. These data provide evidence that a subpopulation of WDR neurons is the dorsal horn cell type most sensitive to small increases in noxious heat in the 45-49 degrees C temperature range and provides the most information about stimulus intensity. The findings support the view that nociceptive neurons have the capacity to precisely encode stimulus features in the noxious range and that WDR neurons are likely to participate in the monkeys' ability to perceive the intensity of such stimuli.


1993 ◽  
Vol 69 (2) ◽  
pp. 318-328 ◽  
Author(s):  
D. A. Simone ◽  
M. E. Hanson ◽  
N. A. Bernau ◽  
B. H. Pubols

1. Responses to noxious mechanical and thermal stimuli were examined in 48 thalamic neurons in barbiturate or chloralose-anesthetized raccoons, with special attention to neurons whose peripheral receptive fields (RFs) included glabrous skin of the forepaw. Recording loci were in the core of the ventrobasal complex (VB; n = 32), its ventral or dorsal border (n = 5), or the medial division of the posterior nuclear group (POm; n = 11). 2. Twenty-one VB neurons and 7 POm neurons were classed as wide dynamic range (WDR), whereas 2 VB neurons and 4 POm neurons were classed as nociceptive specific (NS). Response properties of 14 light touch (LT) neurons located in VB were also examined. 3. WDR and NS neurons were not segregated, but rather were intermixed along the ventral and dorsal borders of VB, as well as in POm, and WDR and LT neurons were intermixed in the core of VB. Within the VB core, both LT and WDR neurons were somatotopically organized. 4. All WDR neurons had larger high-threshold than low-threshold RFs, and this difference was greater for POm neurons than for VB neurons. RF areas of LT neurons and low-threshold RF areas of WDR neurons were comparable to those previously reported for raccoon VB units. 5. Out of 25 WDR cells tested, 20 had heat thresholds > 53 degrees C; the range of thresholds in the remaining 5 was 49-53 degrees C. Four out of five NS neurons tested had heat thresholds > 53 degrees C; the threshold of the fifth was 51 degrees C. Of the six neurons with heat thresholds < or = 53 degrees C, two each were in the core of VB, along the border of VB, and in POm. 6. Sensitization to heat after a mild heat injury to the glabrous RF (53 degrees C for 90 s, or 55 degrees C for 30 s) occurred in 8 out of 16 neurons tested, and persisted for up to 2 h. Median thresholds decreased from > 53 degrees C before injury to 47 degrees C after injury, and responses to suprathreshold stimuli were enhanced. There was a significantly greater likelihood (P = 0.02) for sensitization to occur in POm neurons (6/7) than in VB neurons (2/9). 7. It is suggested that a small proportion of neurons located in VB and POm contribute to the sensation of heat pain. Furthermore, sensitization of these neurons may contribute to heat hyperalgesia after an injury to glabrous skin.


2015 ◽  
Vol 114 (4) ◽  
pp. 2528-2534 ◽  
Author(s):  
T. Akiyama ◽  
M. Nagamine ◽  
A. Davoodi ◽  
M. Iodi Carstens ◽  
F. Cevikbas ◽  
...  

Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and algesic stimuli or spinal superfusion of bombesin, a homolog of gastrin-releasing peptide (GRP) that excites spinal itch-signaling neurons. Single-unit recordings were made from lumbar dorsal horn neurons in pentobarbital-anesthetized C57BL/6 mice. We searched for units that exhibited elevated firing after id injection of ET-1 (1 μg/μl). Responsive units were further tested with mechanical stimuli, bombesin (spinal superfusion, 200 μg·ml−1·min−1), heating, cooling, and additional chemicals [histamine, chloroquine, allyl isothiocyanate (AITC), capsaicin]. Of 40 ET-1-responsive units, 48% responded to brush and pinch [wide dynamic range (WDR)] and 52% to pinch only [high threshold (HT)]. Ninety-three percent responded to noxious heat, 50% to cooling, and >70% to histamine, chloroquine, AITC, and capsaicin. Fifty-seven percent responded to bombesin, suggesting that they participate in spinal itch transmission. That most ET-1-sensitive spinal neurons also responded to pruritic and algesic stimuli is consistent with previous studies of pruritogen-responsive dorsal horn neurons. We previously hypothesized that pruritogen-sensitive neurons signal itch. The observation that ET-1 activates nociceptive neurons suggests that both itch and pain signals may be generated by ET-1 to result in simultaneous sensations of itch and pain, consistent with observations that ET-1 elicits both itch- and pain-related behaviors in animals and burning itch sensations in humans.


1989 ◽  
Vol 62 (4) ◽  
pp. 907-916 ◽  
Author(s):  
C. J. Woolf ◽  
A. E. King

1. Intracellular recordings have been made from 76 neurons in the dorsal horn of the fourth and fifth lumbar segments of the spinal cord in decerebrate-spinal rats. The locations of the neurons were identified after horseradish peroxidase (HRP) ionophoresis (n = 18) or calculated from depth readings (n = 58). Sixty-nine of the neurons were found or estimated to lie within the deep dorsal horn (laminae III-V), with the remaining 7 in laminae I and II. 2. Background excitatory activity was present in all the neurons in the absence of peripheral mechanical stimuli. In 22 neurons, this consisted only of subthreshold excitatory postsynaptic potentials (EPSPs), but in 54, a proportion of the EPSPs reached threshold, producing a spontaneous spike discharge (frequency 0.2-50 Hz) that had a rhythmic component in six cells. Spontaneous hyperpolarizations occurred but were uncommon (n = 10). 3. All the neurons had excitatory cutaneous mechanoreceptive fields on the ipsilateral hindlimb. The receptive fields, defined in terms of action-potential discharge, could be subdivided into two areas: a high-probability "firing zone," where skin stimulation elicited an action-potential discharge above the mean + 1 SD of the background activity; and a low-probability firing fringe, where the stimulus elicited a distinct subthreshold depolarization, but the action-potential response fell within the variability of the background discharge. 4. Mechanical stimulation in the middle of the firing zone in all cells generated both supra- and subthreshold excitatory responses, with the former predominating. As the stimuli were applied progressively farther away from the center of the firing zone, the subthreshold component became relatively more prominent. 5. Fifty percent of the 15 neurons that were recorded from for sufficient time (greater than 30 min) to enable the presence, extent, and characteristics of subthreshold responses to be examined in detail were found to have a low-probability firing fringe to their receptive fields. The response to stimulation within this fringe typically consisted of high-frequency, low-amplitude PSPs riding on a sustained depolarization, with an action-potential discharge that could not readily be distinguished from the spontaneous activity. The size of the fringe ranged from a small area adjacent to the firing zone to almost the entire hindlimb. 6. The firing zones of 20 neurons were low-threshold only and in 5 cells were high-threshold only. The majority of neurons were multireceptive, responding both to low- and high-intensity stimuli (n = 51).(ABSTRACT TRUNCATED AT 400 WORDS)


1992 ◽  
Vol 68 (2) ◽  
pp. 384-391 ◽  
Author(s):  
J. X. Hao ◽  
X. J. Xu ◽  
Y. X. Yu ◽  
A. Seiger ◽  
Z. Wiesenfeld-Hallin

1. The activity of 197 single dorsal horn neurons was recorded extracellularly in the spinal cord of decerebrate, spinalized, unanesthetized rats. The response properties of 174 wide dynamic range (WDR) neurons to electrical, mechanical, and thermal stimulation in three groups of rats were studied:normal, 1-4 days after transient spinal cord ischemia induced photochemically by laser irradiation when the rats exhibited behavioral hypersensitivity to mechanical stimuli (allodynia), and 10-20 days after spinal ischemia when the allodynia had ceased. 2. In normal rats, the responses of dorsal horn WDR neurons to suprathreshold electrical stimulation of their receptive fields consisted of a short-latency (A) and a long-latency (C) response. In 77% of the neurons (57/74), there was a separation between the A- and C-fiber responses. The response threshold (defined as 20% increase in neuronal discharges above background activity) to mechanical stimulation applied with calibrated von Frey hairs was 13.8 g, and the discharges of these neurons to graded stimulation increased linearly. 3. In 68% of WDR neurons in allodynic rats (38/56), the response to suprathreshold electrical stimuli was a single burst with no separation between A- and C-fiber responses. The magnitude and duration of the response were significantly increased compared with those recorded in normal rats. The sensitivity of these neurons to mechanical stimulation was also greatly increased, expressed by a lowered threshold (2.1 +/- 0.3 g, mean +/- SE) and a shift to the left of the nonlinear stimulus-response curve. The background activity of the neurons and the size of the receptive fields were, however, unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)


1992 ◽  
Vol 68 (2) ◽  
pp. 392-396 ◽  
Author(s):  
J. X. Hao ◽  
X. J. Xu ◽  
Y. X. Yu ◽  
A. Seiger ◽  
Z. Wiesenfeld-Hallin

1. In the companion paper, we described a state of hypersensitivity that developed in dorsal horn wide dynamic range (WDR) neurons in rats after transient spinal cord ischemia. Thus the WDR neurons exhibited lower threshold and increased responses to low-intensity mechanical stimuli. The response pattern of these neurons to suprathreshold electrical stimulation was also changed. Notably, the response to A-fiber input was increased. No change in response to thermal stimulation was found before and after spinal cord ischemia. 2. In normal rats, the gamma-aminobutyric acid (GABA)B agonist baclofen (0.1 mg/kg ip) administered 1-3 h before neuronal recording suppressed the responses of WDR neurons to high-intensity mechanical pressure without influencing the threshold and the responses to lower-intensity stimuli. 3. In allodynic rats, similar pretreatment with baclofen totally reversed the hypersensitivity of the WDR neurons to mechanical stimuli and normalized the response pattern of neurons to electrical stimulation. 4. The GABAA receptor agonist muscimol (1 mg/kg ip) did not influence the response of WDR neurons in either normal or allodynic animals. 5. The present results demonstrated that the GABAB agonist baclofen is effective in reversing the hypersensitivity of dorsal horn WDR neurons to low-intensity mechanical stimulation after transient spinal cord ischemia, indicating that dysfunction of the GABAergic inhibitory system may be responsible for the development of neuronal hypersensitivity. 6. It is suggested that GABAergic interneurons exert a tonic presynaptic inhibitory control, through baclofen-sensitive B-type GABA receptors, on input from low-threshold mechanical afferents, and that disruption of this control may result in painful reaction to innocuous stimuli (allodynia).


2001 ◽  
Vol 86 (6) ◽  
pp. 2868-2877 ◽  
Author(s):  
Koichi Iwata ◽  
Takao Imai ◽  
Yoshiyuki Tsuboi ◽  
Akimasa Tashiro ◽  
Akiko Ogawa ◽  
...  

The effects of inferior alveolar nerve (IAN) transection on escape behavior and MDH neuronal activity to noxious and nonnoxious stimulation of the face were precisely analyzed. Relative thresholds for escape from mechanical stimulation applied to the whisker pad area ipsilateral to the transection were significantly lower than that for the contralateral and sham-operated whisker pad until 28 days after the transection, then returned to the preoperative level at 40 days after transection. A total of 540 neurons were recorded from the medullary dorsal horn (MDH) of the nontreated naive rats [low-threshold mechanoreceptive (LTM), 27; wide dynamic range (WDR), 31; nociceptive specific (NS), 11] and sham-operated rats with skin incision (LTM, 34; WDR, 30; NS, 23) and from the ipsilateral (LTM, 82; WDR, 82; NS, 31) and contralateral MDH relative to the IAN transection (LTM, 77; WDR, 82; NS, 33). The electrophysiological properties of these neurons were precisely analyzed. Background activity of WDR neurons on the ipsilateral side relative to the transection was significantly increased at 2–14 days after the operation as compared with that of naive rats. Innocuous and noxious mechanical-evoked responses of LTM and WDR neurons were significantly enhanced at 2–14 days after IAN transection. The mean area of the receptive fields of WDR neurons was significantly larger on the ipsilateral MDH at 2–7 days after transection than that of naive rats. We could not observe any modulation of thermal responses of WDR and NS neurons following IAN transection. Also, no MDH neurons were significantly affected in the rats with sham operations. The present findings suggest that the increment of neuronal activity of WDR neurons in the MDH following IAN transection may play an important role in the development of the mechano-allodynia induced in the area adjacent to the area innervated by the injured nerve.


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