scholarly journals Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin

2016 ◽  
Vol 116 (1) ◽  
pp. 159-170 ◽  
Author(s):  
Ryan Patel ◽  
Anthony H. Dickenson
Keyword(s):  
Dynamic Range ◽  
Spinal Nerve ◽  
Population Coding ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Noxious Heat ◽  
Posterior Thalamus ◽  
Central Processing ◽  
Wdr Neurons

Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a “WDR phenotype.” After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity.

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. I. Locations of antidromically identified axons in the thalamus and hypothalamus

1994 ◽  
Vol 71 (3) ◽  
pp. 959-980 ◽  
Author(s):  
R. J. Dado ◽  
J. T. Katter ◽  
G. J. Giesler
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Ventral Horn ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Noxious Heat ◽  
Antidromic Activation ◽  
Posterior Thalamus ◽  
Electrolytic Lesions ◽  
Nociceptive Input

1. Seventy-seven neurons in the cervical enlargement of rats anesthetized with urethan were initially antidromically activated using currents < or = 30 microA from the contralateral posterior thalamus. A goal of these experiments was to determine the course of physiologically characterized spinal axons within the diencephalon. Therefore, in 38 cases, additional antidromic mapping was done throughout the mediolateral extent of the diencephalon at multiple anterior-posterior planes. 2. Electrolytic lesions marking the recording sites were recovered for 71 neurons. Thirty-one were located in the superficial dorsal horn (SDH); 39 were in nucleus proprius or the lateral reticulated area of the deep dorsal horn (DDH), and one was in the ventral horn. 3. Eight of 38 (21%) neurons that were tested for more anterior projections could only be antidromically activated with currents < or = 30 microA from sites in the contralateral posterior thalamus. Such neurons are referred to as spinothalamic tract (STT) neurons. Lesions marking the lowest threshold points for antidromic activation were located in or near the posterior thalamic group (Po). At more anterior levels, considerably higher currents were required for antidromic activation or it was not possible to activate the neurons with currents up to 500 microA. Four of these neurons were physiologically characterized and each responded preferentially to noxious mechanical stimuli (wide dynamic range, WDR). Each of the three neurons that were tested responded to noxious heat stimuli. These findings confirm anatomic studies that have shown that a number of STT axons terminate in Po and suggest that such axons that originate in the cervical enlargement carry nociceptive input from the upper extremity. 4. In 15 cases, electrode penetrations were made systematically throughout much of the contralateral ventrobasal complex (VbC). In 17 cases, penetrations were made throughout the intralaminar nuclei contralaterally, including the central lateral nucleus (CL). Surprisingly, only one of the examined axons was antidromically activated with low currents from CL and one from VbC, although both of these nuclei are known to receive sizeable inputs from the STT. 5. Many of the axons (27 of the 38 tested, 71%) that were initially antidromically activated from the contralateral posterior thalamus could also be antidromically activated with low currents (< or = 30 microA) and at increased latencies from sites located anteriorly in the contralateral hypothalamus. Such neurons are referred to as spinothalamic tract/spinohypothalamic tract (STT/SHT) neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

scholarly journals Termination Zones of Functionally Characterized Spinothalamic Tract Neurons Within the Primate Posterior Thalamus

2008 ◽  
Vol 100 (4) ◽  
pp. 2026-2037 ◽  
Author(s):  
Steve Davidson ◽  
Xijing Zhang ◽  
Sergey G. Khasabov ◽  
Donald A. Simone ◽  
Glenn J. Giesler
Keyword(s):  
Dynamic Range ◽  
Lumbar Spinal Cord ◽  
High Threshold ◽  
Chemical Information ◽  
Thalamic Nuclei ◽  
Spinothalamic Tract ◽  
Noxious Heat ◽  
Antidromic Activation ◽  
Posterior Thalamus ◽  
Medial Geniculate

The primate posterior thalamus has been proposed to contribute to pain sensation, but its precise role is unclear. This is in part because spinothalamic tract (STT) neurons that project to the posterior thalamus have received little attention. In this study, antidromic mapping was used to identify individual STT neurons with axons that projected specifically to the posterior thalamus in Macaca fascicularis. Each axon was located by antidromic activation at low stimulus amplitudes (<30 μA) and was then surrounded distally by a grid of stimulating points in which 500-μA stimuli were unable to activate the axon antidromically, thereby indicating the termination zone. Several nuclei within the posterior thalamus were targets of STT neurons: the posterior nucleus, suprageniculate nucleus, magnocellular part of the medial geniculate nucleus, and limitans nucleus. STT neurons projecting to the ventral posterior inferior nucleus were also studied. Twenty-five posterior thalamus-projecting STT neurons recorded in lumbar spinal cord were characterized by their responses to mechanical, thermal, and chemical stimuli. Sixteen of 25 neurons were recorded in the marginal zone and the balance was located within the deep dorsal horn. Thirteen neurons were classified as wide dynamic range and 12 as high threshold. One-third of STT neurons projecting to posterior thalamus responded to noxious heat (50°C). Two-thirds of those tested responded to cooling. Seventy-one percent responded to an intradermal injection of capsaicin. These data indicate that the primate STT transmits noxious and innocuous mechanical, thermal, and chemical information to multiple posterior thalamic nuclei.

Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys

1979 ◽  
Vol 42 (5) ◽  
pp. 1354-1369 ◽  
Author(s):  
J. M. Chung ◽  
D. R. Kenshalo ◽  
K. D. Gerhart ◽  
W. D. Willis
Keyword(s):  
Dynamic Range ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Noxious Heat ◽  
C Fibers ◽  
C Fiber ◽  
Excitatory Action ◽  
Low Threshold ◽  
Lateral Nucleus

1. The responses of spinothalamic tract cells in the lumbosacral spinal cords of anesthetized monkeys were examined following electrical stimulation of the sural nerve or the application of noxious thermal and mechanical stimuli to the skin on the lateral aspect of the foot. 2. The spinothalamic tract neurons were classified as wide dynamic range (WDR), high-threshold (HT), or low-threshold (LT) cells on the basis of their responses to mechanical stimuli. 3. All of the WDR and HT spinothalamic tract cells tested responded to volleys in A- and C-fibers. However, strong C-fiber responses were more common in HT than in WDR cells. 4. The responses atributed to C-fibers were graded with the size of the C-fiber volley. The latencies of the responses attributed to C-fibers indicated that the fastest afferents involved had a mean conduction velocity of 0.9 m/s. The responses remained after anodal blockade of conduction in A-fibers. 5. Temporal summation of the responses of spinothalamic tract cells was demonstrated both to brief trains of stimuli at 33 Hz and to single stimuli repeated at 1- to 2-s intervals. The latter phenomenon is often called "windup." 6. The responses of several spinothalamic tract cells to noxious heat pulses could still be elicited during anodal blockade of conduction in A-fibers. Similarly, it was possible to demonstrate an excitatory action of noxious mechanical stimuli despite interference with conduction in A-fibers by anodal current. 7. The cells investigated were located either in the marginal zone or in the layers of the dorsal horn equivalent to Rexed's laminae IV-VI in the cat. The cells were generally activated antidromically from the caudal part of the ventral posterior lateral nucleus of the thalamus.

Effects of TRPA1 Agonists Mustard Oil and Cinnamaldehyde on Lumbar Spinal Wide-Dynamic Range Neuronal Responses to Innocuous and Noxious Cutaneous Stimuli in Rats

2008 ◽  
Vol 99 (2) ◽  
pp. 415-425 ◽  
Author(s):  
Austin W. Merrill ◽  
Jason M. Cuellar ◽  
Justin H. Judd ◽  
Mirela Iodi Carstens ◽  
E. Carstens
Keyword(s):  
Dynamic Range ◽  
Allyl Isothiocyanate ◽  
Mustard Oil ◽  
Peripheral Sensitization ◽  
Mechanical Stimuli ◽  
Wide Dynamic Range ◽  
Noxious Heat ◽  
Before And After ◽  
Wdr Neurons ◽  
Lumbar Spinal

Mustard oil [allyl isothiocyanate (AITC)] and cinnamaldehyde (CA), agonists of the ion channel TRPA1 expressed in sensory neurons, elicit a burning sensation and heat hyperalgesia. We tested whether these phenomena are reflected in the responses of lumbar spinal wide-dynamic range (WDR) neurons recorded in pentobarbital-anesthetized rats. Responses to electrical and graded mechanical and noxious thermal stimulation were tested before and after cutaneous application of AITC or CA. Repetitive application of AITC initially increased the firing rate of 52% of units followed by rapid desensitization that persisted when AITC was reapplied 30 min later. Responses to noxious thermal, but not mechanical, stimuli were significantly enhanced irrespective of whether the neuron was directly activated by AITC. Windup elicited by percutaneous or sciatic nerve electrical stimulation was significantly reduced post-AITC. These results indicate that AITC produced central inhibition and peripheral sensitization of heat nociceptors. CA did not directly excite WDR neurons, and significantly enhanced responses to noxious heat while not affecting windup or responses to skin cooling or mechanical stimulation, indicating a peripheral sensitization of heat nociceptors.

Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. II. Responses to innocuous and noxious mechanical and thermal stimuli

1994 ◽  
Vol 71 (3) ◽  
pp. 981-1002 ◽  
Author(s):  
R. J. Dado ◽  
J. T. Katter ◽  
G. J. Giesler
Keyword(s):  
Dorsal Horn ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Ventral Horn ◽  
Zona Incerta ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Noxious Stimuli ◽  
Wdr Neurons

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)

Responses of spinothalamic tract cells to mechanical and thermal stimulation of skin in rats with experimental peripheral neuropathy

1992 ◽  
Vol 67 (6) ◽  
pp. 1562-1573 ◽  
Author(s):  
J. Palecek ◽  
V. Paleckova ◽  
P. M. Dougherty ◽  
S. M. Carlton ◽  
W. D. Willis
Keyword(s):  
Dynamic Range ◽  
Background Activity ◽  
Thermal Stimulation ◽  
Spontaneous Pain ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
High Background ◽  
Threshold Temperatures ◽  
Thermal Stimuli ◽  
Stimulation Of

1. Responses of spinothalamic tract (STT) neurons to mechanical and thermal stimulation of skin were recorded under urethane and pentobarbital anesthesia in 12 control rats and in 20 rats with experimental neuropathy. Activity of the STT cells in neuropathic rats was recorded 7, 14, and 28 days after inducing the neuropathy by placing four loose ligatures on the sciatic nerve. 2. All neuropathic animals showed guarding of the injured hindpaw and a shorter withdrawal latency from a radiant heat source of the neuropathic hindpaw than that of the sham-operated paw. 3. STT neurons in neuropathic animals showed the most profound changes 7 and 14 days after the nerve ligation. When compared with STT cells in unoperated animals, approximately half of the neurons had high background activity, responses to innocuous stimuli represented a larger percentage of the total evoked activity in wide dynamic range neurons, and the occurrence and magnitude of afterdischarges to mechanical and thermal stimuli were increased. 4. The mean threshold temperatures of heat-evoked responses of the STT cells in neuropathic animals were not different than those of cells from control animals. However, in neuropathic rats, cells reacting to small heat stimuli usually already had afterdischarges. 5. The increase in the background activity of STT cells is consistent with behavioral observations of spontaneous pain in this model of experimental neuropathy. Furthermore, the afterdischarges of STT cells may parallel the prolonged paw withdrawal in response to noxious stimuli that is seen in these animals and that is evidence for hyperalgesia. However, there was no indication of a lowered threshold for thermal stimuli as might be expected if the animals have thermal allodynia. Mechanical allodynia may have resulted from a relative increase in responsiveness to innocuous mechanical stimuli. However, responses to noxious mechanical stimuli were reduced compared with control, at least at 28 days after the ligation. Peripheral and central mechanisms responsible for the changes in responses of STT cells in neuropathic animals are suggested.

Changes in tonic descending inhibition of spinal neurons with articular input during the development of acute arthritis in the cat

1991 ◽  
Vol 66 (3) ◽  
pp. 1021-1032 ◽  
Author(s):  
H. G. Schaible ◽  
V. Neugebauer ◽  
F. Cervero ◽  
R. F. Schmidt
Keyword(s):  
Acute Inflammation ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Response Threshold ◽  
Mechanical Stimuli ◽  
Spinal Neurons ◽  
Descending Inhibition ◽  
Intact State ◽  
Wdr Neurons ◽  
Alpha Chloralose

1. In 15 alpha-chloralose-anesthetized cats we studied the presence of tonic descending inhibition (TDI) of spinal neurons with input from the knee and its modulation during an acute inflammation of this joint. TDI of spinal neurons with articular input was assessed by applying reversible cold blocks to the lower thoracic cord. The amount of descending inhibition was estimated from the induction and/or increase of resting discharges and of the responses to mechanical stimuli to the knee and other structures during the transitory and reversible blocks. In each experiment one or a few neurons were investigated while the joint was in normal condition [altogether 15 nociceptive-specific (NS) and 6 wide-dynamic-range (WDR) neurons]. One of the neurons was then selected for long-term recordings during which an acute inflammation in the knee was induced by the intra-articular injection of kaolin and carrageenan. Before and during developing arthritis, cold blocks were applied to examine whether the amount of TDI would change during the inflammatory process. 2. The neurons with input from the normal knee were under TDI because application of the cold block induced or increased resting discharges and the responses to noxious compression of the knee and the adjacent thigh and lower leg. In 10 of 15 NS neurons, the response threshold was lowered into the innocuous range. In 9 of 17 cells tested, the excitatory receptive field expanded to the ipsilateral paw, and 4 neurons became inhibited by paw compression. Seven of 18 neurons tested revealed inhibitory receptive fields on the contralateral leg during cold block. The neurons were located in laminae IV-VII. 3. Fourteen neurons were continuously monitored during development of inflammation, and changes in the effectiveness of TDI were assessed by blocking the cord before and during the development of arthritis. In most neurons baseline resting activity in the intact state of the cord increased while the arthritis developed. This inflammation-evoked enhancement of resting discharges was more pronounced during periods of spinalization. Consequently, the differences between the resting discharges in the cold-blocked and the intact state were progressively enhanced in arthritis. 4. After induction of arthritis, the responses to compression of the knee joint increased in the intact state as well as during cold blocks. In 11 of 14 neurons, the differences between the responses in the spinal and intact state were progressively enlarged during the development of inflammation. A similar result was obtained for flexion of the injected knee.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of Responses of Primate Spinothalamic Tract Neurons to Pruritic and Algogenic Stimuli

2004 ◽  
Vol 91 (1) ◽  
pp. 213-222 ◽  
Author(s):  
Donald A. Simone ◽  
Xijing Zhang ◽  
Jun Li ◽  
Jun-Ming Zhang ◽  
Christopher N. Honda ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Intradermal Injection ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Wide Dynamic Range ◽  
Antidromic Activation ◽  
Lateral Nucleus ◽  
Maximal Time

We investigated the role of mechanosensitive spinothalamic tract (STT) neurons in mediating 1) the itch evoked by intradermal injection of histamine, 2) the enhanced sense of itch evoked by innocuous stroking (alloknesis), and 3) the enhanced pain evoked by punctate stimulation (hyperalgesia) of the skin surrounding the injection site. Responses to intradermal injections of histamine and capsaicin were compared in STT neurons recorded in either the superficial or the deep dorsal horn of the anesthetized monkey. Each neuron was identified by antidromic activation from the ventral posterior lateral nucleus of thalamus and classified by its initial responses to mechanical stimuli as wide dynamic range (WDR) or high-threshold (HT). Approximately half of the WDRs and one of the HTs responded weakly to histamine, some with a duration > 5 min, the maximal time allotted. WDRs but not HTs exhibited a significant increase in response to punctate stimulation after histamine consistent with their possible role in mediating histamine-induced hyperalgesia. Neither type of neuron exhibited significant changes in response to stroking, consistent with their unlikely role in mediating alloknesis. Furthermore, nearly all STT neurons exhibited vigorous and persistent responses to capsaicin, after which they became sensitized to stroking and to punctate stimulation. We conclude that the STT neurons in our sample are more likely to contribute to pain, allodynia, and hyperalgesia than to itch and alloknesis.

Wide dynamic range but not nociceptive-specific neurons encode multidimensional features of prolonged repetitive heat pain

1993 ◽  
Vol 69 (3) ◽  
pp. 703-716 ◽  
Author(s):  
R. C. Coghill ◽  
D. J. Mayer ◽  
D. D. Price
Keyword(s):  
Spinal Cord ◽  
Pain Intensity ◽  
Dynamic Range ◽  
Initial Period ◽  
Substantial Reduction ◽  
Nociceptive Stimulation ◽  
Wide Dynamic Range ◽  
Noxious Heat ◽  
Wdr Neurons ◽  
Pain Unpleasantness

1. To better characterize temporal and spatial mechanisms involved in the coding of prolonged nociceptive stimuli in the spinal cord, the responses of dorsal horn wide dynamic range (WDR) and nociceptive-specific (NS) neurons to prolonged, repetitive noxious heat stimuli (45–49 degrees C) were examined in unanesthetized, spinal cord transected rats. To relate these neuronal responses to conscious dimensions of pain, human subjects were presented with identical types of prolonged, repetitive stimuli, so that psychophysical ratings of pain intensity and pain unpleasantness could be compared with the magnitudes and temporal features of the responses of NS and WDR neurons. 2. WDR neurons exhibited high rates of impulse discharge throughout 45 min of repetitive nociceptive stimulation, with only partial reduction (31% decrease from peak rates) occurring after 2 min of stimulation. In sharp contrast, NS neurons stimulated under the same conditions displayed substantial reduction of firing (73% decrease from peak rates) after a brief, initial period of activity that occurred within 2 min after onset of stimulation. Psychophysical ratings of pain intensity and pain unpleasantness, like the responses of WDR neurons, did not decrease substantially from initial levels during 7 min of painful stimulation. Furthermore, these ratings remained at high levels during time periods where the impulse frequencies of NS neurons were only at 27% of maximal levels. 3. Graded nociceptive stimuli were employed to characterize the ability of WDR neurons to encode nociceptive intensity over long durations of repetitive stimulation and to delineate further the relationship between WDR and psychophysical responses. Both WDR discharge frequencies and psychophysical ratings of pain intensity and unpleasantness increased in a monotonic manner to graded increases in stimulus temperatures. 4. These results indicate that pain does not decrease substantially during the course of prolonged, repetitive nociceptive stimulation. The fact that the responses of NS neurons decline significantly, whereas both WDR and psychophysical responses do not, suggests that WDR neurons alone are sufficient to evoke both sensory intensity and affective responses to prolonged pain. Furthermore, because subjects could localize and qualitatively describe pain at times when responses of NS neurons were minimal, WDR neurons alone can encode some spatial and qualitative aspects of pain.

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