Alterations in Ascending Dorsal Horn Neurons by a Surgical Incision in the Rat Foot

2000 ◽  
Vol 93 (5) ◽  
pp. 1294-1302 ◽  
Author(s):  
Erik P. Vandermeulen ◽  
Timothy J. Brennan
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Background Activity ◽  
Mechanical Stimuli ◽  
Behavioral Experiments ◽  
Surgical Incision ◽  
Dorsal Horn Neurons ◽  
Low Threshold ◽  
Plantar Incision ◽  
Wdr Neurons

Background Little is known about the mechanisms of pain caused by a surgical incision. The authors have developed a rat model of postoperative pain characterized by decreased withdrawal thresholds to punctate mechanical stimuli after plantar incision. The present studies examined the response characteristics of dorsal horn neurons receiving input from the plantar aspect of the foot before and after a plantar incision placed adjacent to the low threshold area of the receptive field (RF). Methods Individual dorsal horn neurons from the lumbar enlargement were antidromically identified and characterized as low threshold, wide dynamic range (WDR), and high threshold (HT) based on their responses to brush and pinch. Thresholds (in millinewtons), the pinch RF, and stimulus-response functions (SRFs) to von Frey filaments characterized the neurons. SRFs were analyzed using area under the curve. Changes in background activity, punctate mechanical thresholds, SRFs, and RF were recorded after an incision was made adjacent to the most sensitive area of the RF. Results In all cells, an incision increased background activity; this remained elevated in 3 of 9 HT and 16 of 28 WDR neurons 1 h later. The SRFs were enhanced in 10 of 27 WDR neurons and in 2 of 8 HT cells after incision. Only the WDR neurons were responsive to filaments that produced withdrawal responses after incision in behavioral experiments. Increases in the RFs outside of the injured area occurred after incision in 15 of 29 WDR and 2 of 9 HT cells. Conclusion A plantar incision caused dorsal horn cell activation and central sensitization. Because the threshold of HT neurons did not decrease to the range of the withdrawal responses in behavioral experiments, particular WDR dorsal horn neurons likely contribute to the reduced withdrawal threshold observed in behavioral experiments. Both WDR and HT neurons are capable of transmitting enhanced responses to strong punctate mechanical stimuli after incision.

Incision-induced Changes in Receptive Field Properties of Rat Dorsal Horn Neurons 

1999 ◽  
Vol 91 (3) ◽  
pp. 772-772 ◽  
Author(s):  
Peter K. Zahn ◽  
Timothy J. Brennan
Keyword(s):  
Receptive Field ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
Background Activity ◽  
Mechanical Stimulus ◽  
High Threshold ◽  
Pain Mechanisms ◽  
Dorsal Horn Neurons ◽  
Plantar Aspect ◽  
Wdr Neurons

Background To learn more about pain mechanisms produced by surgery, responses of wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons were studied before and after an incision. For this study, an incision was made in a mechanically insensitive area of the receptive field (RF) of the dorsal horn neuron in the plantar aspect of the foot and changes in mechanical response properties were studied. Methods Action potentials from single dorsal horn neurons were recorded in halothane anesthetized rats and these neurons were characterized as WDR or HT. Changes in background activity and responses to a variety of mechanical stimuli adjacent to the incision, distant to the injury, and in areas throughout the hindquarters were recorded. Results Fifty neurons were recorded (29 WDR, 21 HT cells); only nine of these had a sustained increase in background activity after incision. Marked decreases in threshold to von Frey filaments applied adjacent to the wound occurred in 9 of 28 WDR neurons but in none of 21 HT cells. Von Frey filament thresholds distant to the incision were largely not changed. A blunt mechanical stimulus activated 18 of 22 WDR neurons when applied directly on the incision. HT cells were largely not excited by this mechanical stimulus after incision. The RF to pinch was enlarged in 31 neurons to include areas outside the injury. Pinch RFs of both WDR and HT cells expanded. Conclusion These results suggest that incisions in mechanically insensitive areas of the RF of dorsal horn neurons produced little change in background activity; expansion of pinch RFs outside the injury was common. Changing a mechanically insensitive area of the RF of WDR neurons to a mechanically sensitive area by an incision could contribute to pain behaviors that indicate primary mechanical hyperalgesia in behavioral studies.

scholarly journals Electrophysiological Changes in Adult Rat Dorsal Horn Neurons After Neonatal Peripheral Inflammation

2003 ◽  
Vol 90 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Yuan Bo Peng ◽  
Qing Dong Ling ◽  
M. A. Ruda ◽  
Daniel R. Kenshalo
Keyword(s):  
Spinal Cord ◽  
Receptive Field ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
High Threshold ◽  
Peripheral Inflammation ◽  
Mechanical Stimuli ◽  
Neonatal Rats ◽  
Adult Rats ◽  
Dorsal Horn Neurons

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.

A comparative study of the changes in receptive-field properties of multireceptive and nocireceptive rat dorsal horn neurons following noxious mechanical stimulation

1989 ◽  
Vol 62 (4) ◽  
pp. 854-863 ◽  
Author(s):  
J. M. Laird ◽  
F. Cervero
Keyword(s):  
Dorsal Horn ◽  
Mechanical Stimulation ◽  
Receptive Fields ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Dorsal Horn Neurons ◽  
Mechanical Threshold ◽  
Before And After ◽  
Low Threshold ◽  
Noxious Mechanical Stimulation

1. Single-unit electrical activity has been recorded from 42 dorsal horn neurons in the sacral segments of the rat's spinal cord. The sample consisted of 20 multireceptive (class 2) cells with both A- and C-fiber inputs and 22 nocireceptive (class 3) cells. All neurons had cutaneous receptive fields (RFs) on the tail. 2. The RF sizes of the cells and their response thresholds to mechanical stimulation of the skin were determined before and after each of a series of 2-min noxious mechanical stimuli. Up to five such stimuli were delivered at intervals ranging from 10 to 60 min. In most cases, only one cell per animal was tested. 3. The majority of neurons were tested in barbiturate-anesthetized animals. However, to test whether or not this anesthetic influenced the results obtained, experiments were also performed in halothane-anesthetized and decerebrate-spinal preparations. The results from these experiments are considered separately. 4. All of the neurons responded vigorously to the first noxious pinch stimulus and all but one to the rest of the stimuli in the series. The responses of the neurons varied from stimulus to stimulus, but there were no detectable trends in the two groups of cells. 5. The RFs of the class 2 cells showed large increases (624.3 +/- 175.8 mm2, mean +/- SE) after the application of the pinch stimuli. The RFs of the class 3 neurons, which were initially smaller than those of the class 2 cells, either did not increase in size or showed very small increases after the pinch stimuli (38.3 +/- 11.95 mm2, mean +/- SE). 6. Some cells in both groups (6/10 class 2 cells and 7/16 class 3 cells) showed a decrease in mechanical threshold as a result of the noxious mechanical stimulus, but none of the class 3 cells' thresholds dropped below 20 mN into the low-threshold range. 7. The results obtained in the halothane-anesthetized and decerebrate-spinal animals were very similar to those seen in the barbiturate-anesthetized experiments, with the exception that in the decerebrate-spinal animals, the RFs of the class 2 cells were initially larger and showed only small increases.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Hyperalgesia and sensitization of dorsal horn neurons following activation of NK-1 receptors in the rostral ventromedial medulla

2017 ◽  
Vol 118 (5) ◽  
pp. 2727-2744 ◽  
Author(s):  
Sergey G. Khasabov ◽  
Patrick Malecha ◽  
Joseph Noack ◽  
Janneta Tabakov ◽  
Glenn J. Giesler ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
Receptor Activation ◽  
Rostral Ventromedial Medulla ◽  
Dorsal Horn Neurons ◽  
Descending Modulation ◽  
Ventromedial Medulla ◽  
Neurokinin 1 ◽  
Wdr Neurons

Neurons in the rostral ventromedial medulla (RVM) project to the spinal cord and are involved in descending modulation of pain. Several studies have shown that activation of neurokinin-1 (NK-1) receptors in the RVM produces hyperalgesia, although the underlying mechanisms are not clear. In parallel studies, we compared behavioral measures of hyperalgesia to electrophysiological responses of nociceptive dorsal horn neurons produced by activation of NK-1 receptors in the RVM. Injection of the selective NK-1 receptor agonist Sar9,Met(O2)11-substance P (SSP) into the RVM produced dose-dependent mechanical and heat hyperalgesia that was blocked by coadministration of the selective NK-1 receptor antagonist L-733,060. In electrophysiological studies, responses evoked by mechanical and heat stimuli were obtained from identified high-threshold (HT) and wide dynamic range (WDR) neurons. Injection of SSP into the RVM enhanced responses of WDR neurons, including identified neurons that project to the parabrachial area, to mechanical and heat stimuli. Since intraplantar injection of capsaicin produces robust hyperalgesia and sensitization of nociceptive spinal neurons, we examined whether this sensitization was dependent on NK-1 receptors in the RVM. Pretreatment with L-733,060 into the RVM blocked the sensitization of dorsal horn neurons produced by capsaicin. c-Fos labeling was used to determine the spatial distribution of dorsal horn neurons that were sensitized by NK-1 receptor activation in the RVM. Consistent with our electrophysiological results, administration of SSP into the RVM increased pinch-evoked c-Fos expression in the dorsal horn. It is suggested that targeting this descending pathway may be effective in reducing persistent pain. NEW & NOTEWORTHY It is known that activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM), a main output area for descending modulation of pain, produces hyperalgesia. Here we show that activation of NK-1 receptors produces hyperalgesia by sensitizing nociceptive dorsal horn neurons. Targeting this pathway at its origin or in the spinal cord may be an effective approach for pain management.

Responses of monkey medullary dorsal horn neurons during the detection of noxious heat stimuli

1989 ◽  
Vol 62 (2) ◽  
pp. 437-449 ◽  
Author(s):  
W. Maixner ◽  
R. Dubner ◽  
D. R. Kenshalo ◽  
M. C. Bushnell ◽  
J. L. Oliveras
Keyword(s):  
Dorsal Horn ◽  
Stimulus Intensity ◽  
Dynamic Range ◽  
Thermal Stimulus ◽  
Mechanical Stimuli ◽  
Behavioral Task ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Medullary Dorsal Horn ◽  
Wdr Neurons

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.

NMDA Channels Together With L-Type Calcium Currents and Calcium-Activated Nonspecific Cationic Currents Are Sufficient to Generate Windup in WDR Neurons

2010 ◽  
Vol 104 (2) ◽  
pp. 1155-1166 ◽  
Author(s):  
P. Aguiar ◽  
M. Sousa ◽  
D. Lima
Keyword(s):  
Membrane Potential ◽  
Dorsal Horn ◽  
Action Potentials ◽  
Dynamic Range ◽  
Calcium Influx ◽  
Calcium Currents ◽  
Factors Affecting ◽  
Dorsal Horn Neurons ◽  
C Fibers ◽  
Wdr Neurons

Windup is characterized as a frequency-dependent increase in the number of evoked action potentials in dorsal horn neurons in response to electrical stimulation of afferent C-fibers. This phenomenon was first described in the mid-60s, but the core mechanisms behind it still remain elusive. Several factors affecting its dynamics have been identified, but the distinction between modulating mechanisms from generating mechanisms is not always clear. Several mechanisms contribute to the excitation of dorsal horn neurons exhibiting windup, and one of our main aims was to help making this distinction. The approach presented here relies on mathematical and computational analysis to study the mechanism(s) underlying windup. From experimentally obtained windup profiles, we extract the time scale of the facilitation mechanisms that may support the characteristics of windup. Guided by these values and using simulations of a biologically realistic compartmental model of a wide dynamic range (WDR) neuron, we are able to assess the contribution of each mechanism for the generation of action potentials windup. We show that the key mechanisms giving rise to windup is the temporal summation of N-methyl-d-aspartate (NMDA) long-lasting postsynaptic responses taking place on top of a membrane potential cumulative depolarization. Calcium-activated nonspecific cationic currents driven by calcium influx from L-type calcium channels and synaptic currents support this cumulative depolarization and plateau formation in WDR neuron membrane potential. The effects of different nonhomogeneous stimulation protocols are explored, and their important role in clarifying many aspects of the windup generation is shown. The models are used to produce several predictions that can be tested experimentally.

Responses of Superficial Dorsal Horn Neurons to Intradermal Serotonin and Other Irritants: Comparison With Scratching Behavior

2002 ◽  
Vol 87 (3) ◽  
pp. 1280-1289 ◽  
Author(s):  
Steven L. Jinks ◽  
E. Carstens
Keyword(s):  
Dorsal Horn ◽  
Time Course ◽  
Dynamic Range ◽  
Neuronal Firing ◽  
Whole Body ◽  
Mustard Oil ◽  
Neural Pathways ◽  
Superficial Dorsal Horn ◽  
Behavioral Experiments ◽  
Dorsal Horn Neurons

Scratching behavior is used to assess itch sensation in animals, but few studies have addressed the relative scratch-inducing capacity of different algesic and pruritic chemicals. Furthermore, central neural mechanisms underlying itch are not well understood. We used electrophysiological and behavioral methods to investigate the ability of several irritant chemicals to excite neurons in the superficial dorsal horn, as well as to elicit scratching, in rats. In anesthetized rats, single neurons in the superficial lumbar dorsal horn, identified by their responsiveness to intracutaneous (ic) histamine, were classified as wide dynamic range (WDR) or nociceptive-specific (NS). Serotonin (5-HT) given ic to the paw excited most (88%) WDR and NS neurons over a prolonged time course (often up to 40 min). 5-HT–evoked responses exhibited significant tachyphylaxis. Most neurons also gave shorter-duration responses to ic capsaicin (92%) and mustard oil (71%). In separate behavioral experiments, significant dose-related hind limb scratching directed at the ic injection site in the back of the neck was elicited by 5-HT over a time course similar to that of evoked neuronal firing. A second 5-HT injection made 40 min later at the same site elicited significantly less scratching. Formalin also elicited scratching that was not dose-related and less than that evoked by 5-HT. 5-HT and Formalin also evoked head or whole-body shakes that were significantly correlated with scratching. Neither histamine, capsaicin, nor vehicle controls elicited significant scratching or shaking. In rats, 5-HT appears to be more pruritogenic than histamine as assessed by scratching and shaking behavior, and excites superficial dorsal horn neurons over a behaviorally relevant time course. However, because most neurons additionally responded to pain-producing stimuli, they are not itch-specific. They might nonetheless contribute to neural pathways that distinguish between pain and itch based on some neural mechanism such as frequency coding.

Responses of rat medullary dorsal horn neurons following intranasal noxious chemical stimulation: effects of stimulus intensity, duration, and interstimulus interval

1993 ◽  
Vol 70 (6) ◽  
pp. 2260-2275 ◽  
Author(s):  
P. Peppel ◽  
F. Anton
Keyword(s):  
Dorsal Horn ◽  
Stimulus Intensity ◽  
Mechanical Stimulation ◽  
Interstimulus Interval ◽  
Dynamic Range ◽  
Chemical Stimulation ◽  
Dorsal Horn Neurons ◽  
C Fibers ◽  
Medullary Dorsal Horn ◽  
Wdr Neurons

1. Most quantitative examinations of nociception are performed with thermal or mechanical stimuli. Because nociceptive processing mechanisms may depend on the modality of the stimuli, comparable studies on chemonociception are necessary. 2. We examined the activity of chemonociceptive medullary dorsal horn neurons in halothane-anesthetized rats. For controlled noxious chemical stimulation, defined CO2 pulses were applied to the nasal mucosa. The effects of stimulus intensity, duration, and interstimulus interval (ISI) were tested by performing three different CO2 stimulation protocols (see below). 3. The recorded neurons were characterized by intranasal and facial stimuli of different modalities. The cells received input from intranasal A delta- and/or C-fibers. All tested neurons also responded to other intranasally applied irritants, e.g., mustard oil. Furthermore, the units were sensitive to intranasal high-threshold mechanical stimulation and to facial mechanical stimulation. According to the properties of their facial mechanoreceptive fields, the units were classified as wide dynamic range (WDR) or nociceptive specific (NS) neurons. The majority of the cells also responded to facially applied noxious heat stimuli, so that most of the recorded neurons were found to be multimodal. Some of the neurons, in addition, had convergent input from primary afferents innervating the maxillary tooth pulps or the cornea and periorbital structures. 4. In the first stimulation protocol we presented four different CO2 concentrations (25, 50, 75, and 100%; stimulus duration 2 s). In total, each concentration was applied 10 times (2 trains of 5 stimuli). Stimulus response functions (SRFs) were computed with average responses to identical stimuli. All but 2 of the 23 tested neurons displayed enhanced responses after stimulation with increasing intensities. In general, WDR cells (n = 15) discharged more vigorously to the same CO2 concentration than NS cells (n = 8). WDR neurons discriminated more reliably between stimulus intensities in the low to moderate range (25–50% CO2) than NS cells. Both categories of neurons, however, discriminated equally well in the moderate- to high-intensity range (50–75% CO2). The discriminatory capacity of WDR and NS neurons was reduced in the highest concentration range (75–100% CO2). The proportion of NS neurons significantly discriminating between these intensities tended to be higher compared with WDR neurons when stimuli were applied with long ISIs (120 s). 5. To examine the effects of the duration of the ISI, identical test sequences were performed with ISIs of 30 and 120 s. (ABSTRACT TRUNCATED AT 400 WORDS)

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
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
Receptive Fields ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Power Functions ◽  
Nociceptive Neurons ◽  
Wdr Neurons ◽  
Sacral Spinal Cord

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)

scholarly journals Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse

2015 ◽  
Vol 114 (4) ◽  
pp. 2528-2534 ◽  
Author(s):  
T. Akiyama ◽  
M. Nagamine ◽  
A. Davoodi ◽  
M. Iodi Carstens ◽  
F. Cevikbas ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Allyl Isothiocyanate ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Superficial Dorsal Horn ◽  
Noxious Heat ◽  
Nociceptive Neurons ◽  
Endothelin 1 ◽  
Dorsal Horn Neurons

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.

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