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1Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4410; 2Department of Psychology, University of Texas at Arlington, Arlington, Texas 76019-0528; 3Center for Scientific Review, National Institutes of Health, Bethesda, Maryland 20814-9692; and 4Cell Biology and Anatomy Laboratory, Cathay General Hospital, Taipei, Taiwan 221, Republic of China
Submitted 11 November 2002; accepted in final form 5 March 2003
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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;
Grubb et al. 1993;
Hylden et al. 1989;
Neugebauer and Schaible 1990;
Owens et al. 1992;
Simone et al. 1991;
Sivilotti et al. 1993;
Thompson et al. 1990,
1992,
1993;
Woolf and King 1990;
Woolf et al. 1994);
2) decreased inhibition by descending systems or inhibitory
interneurons (Bennett 1991;
Bhisitkul et al. 1990;
Castro-Lopes et al. 1993;
Dubner and Ruda 1992;
Lin et al. 1996;
Peng et al. 1996;
Schaible et al. 1991;
Sivilotti and Woolf 1994;
Sugimoto et al. 1990;
Yaksh 1989); and 3)
plastic alteration of the anatomical structures
(Caratsch and Eusebi 1990;
Coggeshall et al. 1991; Devor
et al. 1993,
1994;
Hökfelt et al. 1994;
Koerber et al. 1994;
McLachlan et al. 1993;
Molander et al. 1992;
Shortland and Woolf 1993;
Woolf et al. 1992). In
addition, change in receptor sensitivity may also contribute to the sensory
information process. Opioid receptor binding is developmentally regulated and
substantial postnatal reorganization is observed. Using in vitro
autoradiographical methods, it has been demonstrated that there are
substantial changes of µ-, 
-, and 
-opioid receptor-binding
sites in the spinal cord of rat pups at various postnatal days (P0–P56).
Dorsal horn neurons are highly sensitive to spinal morphine at P21 following
C-fiber stimulation (Rahman et al.
1998).
Evidence has shown that pain in infants' circumcision in the neonatal
period has long-lasting effects (Taddio et al.
1995,
1997). They exhibit a greater
pain response at 4- or 6-mo vaccinations and preoperative treatment with
eutectic mixture of local analgesics (EMLA, Astro Pharmaceutical Products,
Westborough, MA) attenuates the pain response. Following exposure to painful
stimuli, the pain sensitivity of preterm neonates is accentuated by an
increased excitability of nociceptive neurons in the dorsal horn of the spinal
cord (Falcon et al. 1996;
Fitzgerald et al.
1988a,b,
1989). Infants that are
exposed to repeated heel lancing have a cutaneous flexor reflex threshold in
the area of local tissue damage that is half the value of that on the intact
contralateral heel (Fitzgerald et al.
1988a,b).
This decreased threshold has been shown to last for days and/or weeks
(Andrews and Fitzgerald 1994;
Fitzgerald et al. 1989), which
suggests a long-term effect of the previously experienced intense stimuli.
However, there is little evidence demonstrating the long-term effect of early
exposure to noxious stimuli on neuronal activity of the dorsal horn
neurons.
An injection of complete Freund's adjuvant (CFA) can cause long-lasting
inflammation and is a good model of persistent pain. In neonatal rats that
have received a CFA injection in the hind paw, the spatial distribution of
wide dynamic range (WGA)-HRP staining is more extensive at rostral and caudal
levels and the density of staining in the dorsal horn is denser than in
control rats (Ling and Ruda
1998). The purpose of this study was to understand how the
development of nociceptive pathways in the presence of pain due to peripheral
inflammation in neonatal rats affects the response properties of spinal cord
dorsal horn neurons to noxious or innocuous stimulation in adulthood. We
hypothesized that there would be parallel physiological changes in neonatal
rats that were exposed to persistent painful stimulation. Preliminary results
have been reported (Peng et al.
1999; Ruda et al.
2000).
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Time-mated Sprague-Dawley rats (Harlan, Indianapolis, IN) were monitored to
determine the time of birth of rat pups. On postnatal day 1 (P1), male rat
pups received a single, unilateral injection of CFA (2:1, CFA:saline, 25
µl) (Sigma Chemical Co., St. Louis, MO) in the left hind paw. The animals
were allowed to mature to adulthood without further manipulation. All
procedures used in this study were approved by the NIDCR Animal Care and Use
Committee and followed the guidelines for the treatment of animals of the
International Association for the Study of Pain
(Zimmermann 1983).
At 8–10 wk of age, animals were anesthetized with pentobarbital sodium (50 mg/kg, ip). A laminectomy was performed over the lumbosacral enlargement to expose the spinal cord. A catheter was placed in the jugular vein for continuous administration of anesthetics and a tracheotomy allowed insertion of a tracheal cannula for artificial ventilation. Continuous anesthesia was accomplished with 5 mg of pentobarbital sodium per hour. Paralysis of the musculature was achieved by intravenous injection of 0.5 ml pancuronium bromide every 2 h. The end-tidal CO2 was maintained at 3.0 ± 0.5%. The animal's body temperature was maintained at 37°C by a feedback-controlled electric heating blanket.
Data acquisition
EXTRACELLULAR SINGLE CELL RECORDING. For electrophysiological
recordings, a tungsten microelectrode with an impedance of 10–12
M
was used to record extracellular single-unit discharges in the lumbar
enlargement. Dorsal horn neurons were searched on either the left or the right
side while touching or applying pressure by experimenter's fingers on the rat
foot to locate the receptive field and establish a rough estimation of the
category [WDR, low threshold (LT), or high-threshold(HT)] of the neuron.
Dorsal horn neurons were isolated by maximizing the action potentials of a
single cell's orthodromical firing by mechanical stimulation of the receptive
field. Single dorsal horn neurons were recorded in response to graded
intensities of mechanical stimuli that were delivered to the receptive field.
The receptive fields were mapped by applying pressure through the tip of blunt
forceps. As long as the spike to baseline noise was significantly dissociable,
we started recording protocol without specifically selecting cell type, which
was identified after analysis of data. There were usually multiple cells
around the recording electrode. Spike 2 program and 1401 data acquisition
hardware developed by Cambridge Electronic Design (CED) have the ability to
make template for each cell based on its amplitude and shape before recording
starts and it can be done during post-hoc analysis. Usually, one to five cells
could be recorded simultaneously in response to the same stimuli.
Two types of mechanical stimuli were applied to the receptive field.
Innocuous stimulation (brush) was delivered by repeated brushing in a
stereotyped manner with a camel's hair brush. Noxious stimulation (pinch) was
applied with an arterial clip. Responses to the graded mechanical stimuli were
later used to categorize the cells as WDR, HT, or LT neurons (Chung et al.
1979,
1986). WDR neurons responded to
all stimuli; HT neurons responded mostly to pinch with little or no response
to brush, and LT neurons had the most vigorous response to brush with little
or no response to pinch. The SPIKE2 computer software program (CED) was used
to record and analyze the data. Background activity and responses to brush and
pinch were recorded for 10 s each with a 20-s inter-stimulus interval. This
sequence was repeated three times. Recordings were made in the left and right
L4–6 segments alternately to avoid sensitization.
The response to heat stimulation was tested by a feedback-controlled
Peltier device that was lightly placed on the receptive field. The size of the
thermal probe is 10 mm in diameter. The baseline temperature was set at
30°C. Neuronal responses to increasing temperatures between 37 and
49°C were recorded in increments of 2°C. The stimulus duration was 10
s with an inter-stimulus interval of 30 s
(Dubner et al. 1989;
Kenshalo et al. 1989;
Maixner et al. 1989).
RECEPTIVE FIELD CALCULATION. The receptive field mapped by mechanical stimulation was marked on a drawing of the rat hind paw and was proportional to the actual area. The picture was scanned and analyzed by Scion Imaging software, which assigned an arbitrary unit (AU) to the scanned image of the receptive field.
CORD DORSUM POTENTIAL RECORDING. The cord dorsum potentials, produced by electrical stimuli delivered to the left sciatic nerve at 2.5x threshold, were recorded bilaterally from L2 to S3 by a silver ball electrode that was placed on the surface of the spinal cord just medial to the dorsal root entry zone. The threshold was determined by recording the left L5 cord dorsum potential while gradually increasing the stimulus intensity to the left sciatic nerve until the first wave of a compound potential appeared.
Data analysis
The stored digital record of unit activity was retrieved and analyzed off-line. For single neuron recordings, responses to the mechanical stimuli that were applied to the receptive field for 10 s were calculated by subtracting the preceding 10 s of background activity to yield a net increase in discharge rate. The average of three measurements was used. Statistical significance was tested using a two-way analysis of variance (ANOVA) followed by the Tukey test for differences between neonatally treated and untreated groups. A change was judged significant if P < 0.05. All values are presented as mean ± SE.
For cord dorsum potentials, the amplitude and latency of N1 (evoked by the
fastest myelinated fibers), N2 (evoked by the slower myelinated fibers), and P
(a reflection of the depolarization of primary afferent fibers) waves
(Beall et al. 1977) for animals
that received neonatal treatment were measured and compared with control
animals. Statistical significance was tested using a two-way ANOVA followed by
the Tukey test for differences between neonatally treated and control groups.
A change was judged significant if P < 0.05. All values are
presented as mean ± SE.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Extracellular single-cell recordings
Recordings were made from a total of 547 dorsal horn neurons in 17 rats.
Among them, 319 neurons were recorded from 10 control rats and 228 neurons
were recorded from 7 neonatally treated animals. Furthermore, within the 228
neurons, data were obtained from 127 neurons from the left and 101 neurons
were obtained from the right side of the spinal cord. Based on the
classification criteria (Chung et al.
1979,
1986), there were 398 WDR cells
(99 from the left side of neonatally treated rats, 84 from the right side of
neonatally treated rats, and 215 from control rats), 95 HT cells (19 from the
left side of neonatally treated rats, 7 from the right side of neonatally
treated rats, and 69 from control rats), and 54 LT cells (9 from the left side
of neonatally treated rats, 10 from the right side of neonatally treated rats,
and 35 from control rats). The depth of the dorsal horn neurons ranged from
124 to 960 µm (mean: 589.1 ± 11.06 µm) in control rats and from
123 to 1160 µm (mean: 495.12 ± 15.77 µm) in neonatally treated
rats. In each dorsal horn neuron, the background activity and responses to
mechanical brush and pinch were recorded. In some neurons, the size of the
receptive field was documented. In other neurons, the responses to graded heat
stimuli were obtained (see examples in Fig.
1).
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COMPARISON OF THE RECEPTIVE FIELD SIZE. The receptive fields of single dorsal horn neurons were studied in 30 neurons from three neonatally treated rats and 30 neurons from three control rats (Fig. 2). They were all recorded from the left side of the spinal cord. The mean receptive field was significantly larger in the neonatally treated rats (68.3 ± 7.7, with a range of 15.0 to 157.0 AU) than the control rats (28.1 ± 2.6, with a range of 8.9 to 69.0 AU) (P < 0.001). Based on the responsiveness of these 30 neurons in each category, there were 13 and 6 HT neurons, 17 and 23 WDR neurons, 0 and 1 LT neurons in control and neonatally treated animals, respectively. The mean receptive field in neonatally treated animals was significantly larger than the mean receptive field in control animals, 26.04 ± 3.89 and 69.11 ± 15.81 in HT neurons (P = 0.0021), 29.74 ± 3.54 and 68.48 ± 9.36 in WDR neurons (P = 0.0015), respectively.
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RESPONSES TO MECHANICAL STIMULATION. In general, background activity and responses to brush and pinch were significantly higher in neonatally treated rats (3.61 ± 0.33, 16.49 ± 1.27, and 43.81 ± 2.38 spikes/s, respectively) as compared with control animals (1.49 ± 0.12, 9.06 ± 0.66, and 27.24 ± 1.25 spikes/s, respectively). In control rats, background activity and responses to brush and pinch were not significantly different between recordings on the left and right side of the spinal cord. Additionally, there were no differences in responses at different levels of the spinal cord. Further analyses were performed when the dorsal horn neurons were classified into WDR, HT, and LT neurons.
Background activity. Background activity of WDR neurons was significantly higher for neonatally treated rats when recording on the left side (3.6 ± 0.5, ranging from 0 to 19.0 spikes/s, n = 99, P < 0.001) and the right side of the spinal cord (4.0 ± 0.6, ranging from 0 to 32.0 spikes/s, n = 84, P < 0.001) as compared with control rats (1.6 ± 0.1, ranging from 0 to 11.7 spikes/s, n = 215) (Fig. 3A). There were no significant differences of background activity in HT neurons (neonatally treated left side: 3.4 ± 1.2, n = 19; neonatally treated right side: 3.1 ± 2.6, n = 7; control: 1.6 ± 0.3, n = 69, P = 0.116) and LT neurons (neonatally treated left side: 2.6 ± 1.6, n = 9; neonatally treated right side: 1.1 ± 0.3, n = 10; control: 1.0 ± 0.2, n = 35, P = 0.193).
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Response to innocuous mechanical stimulation (brush). The WDR neuronal response to brush was significantly increased in neonatally treated animals when recording on the left side (18.3 ± 2.3, ranging from 0.8 to 124.6 spikes/s, n = 99, P < 0.001), but not on the right side of the spinal cord (14.6 ± 1.9, ranging from 0.7 to 74.1 spikes/s, n = 84, P = 0.064), as compared with neuronal responses in control rats (10.6 ± 0.8, ranging from 0.3 to 75.6 spikes/s, n = 215) (Fig. 3B). The response to brush in LT neurons was significantly increased in neonatally treated animals when recording on the left side (34.6 ± 6.8, ranging from 4.5 to 67.0 spikes/s, n = 9, P < 0.001), but not on the right side of the spinal cord (22.9 ± 6.7, ranging from 3.5 to 69.2 spikes/s, n = 10, P = 0.605), as compared with neuronal responses in control rats (14.1 ± 2.2, ranging from 1.8 to 52.3 spikes/s, n = 35). There were no significant differences in response to brush in HT neurons (neonatally treated left side: 2.6 ± 1.3, n = 19; neonatally treated right side: 2.9 ± 1.0, n = 7; control: 1.7 ± 0.2, n = 69, P = 0.157).
Response to noxious mechanical stimulation (pinch). The WDR neuronal response to pinch was significantly increased in neonatally treated animals when recording on the left side (46.5 ± 4.0, ranging from 5.1 to 198.7 spikes/s, n = 99, P < 0.001) and on the right side of the spinal cord (39.2 ± 4.0, ranging from 4.1 to 228.9 spikes/s, n = 84, P < 0.001), as compared with neuronal responses in control rats (27.2 ± 1.4, ranging from 1.6 to 91.6 spikes/s, n = 215) (Fig. 3C). The HT neuronal response to pinch was significantly increased in neonatally treated animals when recording on the left side (59.3 ± 11.3, ranging from 8.4 to 204.7 spikes/s, n = 19, P < 0.001), but not on the right side of the spinal cord (53.4 ± 17.0, ranging from 24.3 to 151.6spikes/s, n = 7, P = 0.081), as compared with neuronal responses in control rats (36.1 ± 3.1, ranging from 2.4 to 116.9 spikes/s, n = 69). The LT neuronal response to pinch was significantly increased in neonatally treated animals when recording on the left side (28.6 ± 6.9, ranging from 2.6 to 63.1 spikes/s, n = 9, P < 0.001), but not on the right side of the spinal cord (17.5 ± 5.8, ranging from 2.7 to 62.9 spikes/s, n = 10, P = 0.605), as compared with neuronal responses in control rats (10.1 ± 1.8, ranging from 1.1 to 48.6 spikes/s, n = 35).
RESPONSES TO HEAT STIMULATION. The response to heat stimulation was obtained from 24 neurons on the left side of the spinal cord in 7 control rats and 31 neurons on the left side of the spinal cord in 14 neonatally treated rats. There was no difference in response to heat stimuli ranging from 37 to 47°C. The neonatally treated group had significantly increased responding to 49°C (29.5 ± 6.2 spikes/s) as compared with the control group (18.5 ± 4.8 spikes/s, as indicated by "+") (Fig. 4). Within recordings obtained on the left side of the spinal cord in neonatally treated animals, the response to 49°C (29.5 ± 6.2 spikes/s) was significantly higher than background activity (BKG 7.0 ± 1.7 spikes/s) and responses to 37 through 47°C (16.8 ± 4.0 spikes/s, as indicated by "*"). The response to 47°C (16.8 ± 4.0 spikes/s) was significantly higher than responses to 39°C (4.8 ± 1.1 spikes/s) through 43°C (4.6 ± 1.3 spikes/s, as indicated by "*"). Within recordings made on the left side of control rat, the response to 49°C (18.5 ± 4.8 spikes/s) was significantly higher than BKG (4.1 ± 1.4 spikes/s) and responses to 37°C through 43°C (4.9 ± 1.4 spikes/s, as indicated by "*").
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Cord dorsum potential recordings
The cord dorsum potentials were recorded in 32 rats, 16 in control and 16 in neonatally treated animals. Since the left sciatic nerve was stimulated, the cord dorsum potential that was recorded at the fifth left lumbar (LL5) was always the largest in amplitude and was used to normalize the results. The cord dorsum potentials recorded on the right side of the spinal cord were always smaller than recordings on the left side at the same spinal level. Comparisons were made for left and right amplitudes and latencies of N1, N2, and P waves (Fig. 5) at eight spinal levels (L2–S3) between control and neonatally treated animals. There was a trend for an increase in the amplitude and a decrease in the latency of N1, N2, and P waves in neonatally treated rats. However, no significant changes were detected at either the left or the right side of the spinal cord when recording from the L2 to S3 spinal segments (Fig. 5).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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).
A significant lowering of threshold of the reflex in infants ≤35 wk of age
was found following repeated stimulation. Plastic alteration of the anatomical
structures has been reported in chronic pain models
(Caratsch and Eusebi 1990;
Coggeshall et al. 1991; Devor
et al. 1993,
1994;
Hökfelt et al. 1994;
Koerber et al. 1994;
McLachlan et al. 1993;
Molander et al. 1992;
Shortland and Woolf 1993;
Woolf et al. 1992). Under
electron microscope, GAP-43-immunolabeled structures were visualized in
unmyelinated axons, as well as some synaptic terminals and myelinated axons in
the adult rat L4–L5 superficial dorsal horn 2 wk after sciatic nerve
transection. This finding suggests central regenerative processes
(Coggeshall et al. 1991).
Large myelinated fibers terminate in laminae III and IV and small myelinated
and C-fibers terminate in laminae I and II. However, following peripheral
nerve injury, the central terminals of myelinated afferents, including large
A-
-fibers, sprout into lamina II, providing evidence for anatomical
plasticity change and an explanation for mechanical allodynia
(Coggeshall et al. 1996;
Lekan et al. 1996; Woolf et
al. 1992,
1995). In rats that received
an intraplantar CFA injection, a change in the synaptic responses has been
observed (Hylden and Wilcox
1986). Neurons from the substantia gelatinosa (SG) that receive
monosynaptic A--afferent inputs decrease in number, whereas those that
receive monosynaptic A--afferent inputs increase. These results suggest
that following inflammation, a substantial number of A--afferents sprout
into the SG from their original location (laminae III–V). This
reorganization of the sensory pathway may contribute to the mechanisms
involved in the development of hyperalgesia due to inflammation. Cord dorsum potential
Following a neonatal injection of CFA into the hind paw, we found that the
spatial distribution of WGA-HRP staining is much wider at rostral and caudal
levels and the density of staining in the dorsal horn is much more pronounced
(Ling and Ruda 1998;
Ruda et al. 2000). Based on
these anatomical findings, we believe that if there are similar plastic
changes in physiology, it should be easy to detect compound action potentials
as a whole that would reflect the excitability change in the dorsal horn of
the spinal cord. Initially, 8 wk following CFA treatment, we studied cord
dorsum potentials in 16 rats. Compared with 16 control rats, our results show
a trend for increased amplitude and decreased latency in N1, N2, and P waves.
However, no significant changes in amplitude or latency were observed. This
may be due to two factors. First, the measurement of cord dorsum potentials
may not be sensitive enough to detect changes caused by neonatal CFA
treatment. We measured a compound potential, which primarily consisted of
A- and A-fiber components. The distance from the stimulating
electrode at the sciatic nerve to the recording electrode was around
70–80 mm and the C-fiber component could appear at 70- to 80-ms latency,
which might be masked by the P-wave component in the compound action
potential. Perhaps a change occurred at the C-fiber component, but this could
not be demonstrated as a result of technical difficulties. Second, the
positioning of the recording electrode at the entry zone areas of the
corresponding dorsal root on the spinal cord may not be consistent from animal
to animal. Any slight variation of the relative position of the electrode may
result in substantial changes in amplitude and latency. Additionally, the
changing physical properties of the spinal cord surface may influence the
outcome of the measurement. Although the spinal cord was covered with mineral
oil, there is still cerebrospinal fluid that leaks from the upper part of the
open dura or the exudates from the surrounding tissue may have contributed to
the conductivity. Furthermore, the variation of the physical condition of the
animal may be another influencing factor. We found that the cord dorsum
potential at the end of the experiment is always smaller than at the
beginning. Perhaps the unnatural electrical stimulation can mask the actual
change in the spinal cord.
Single neuron recording
Single neuronal recordings of the spinal cord dorsal horn provided
information regarding the effects of neonatal persistent pain at the cellular
level. While searching for a dorsal horn neuron, we did not specifically
search for certain types of neurons. Whenever a clear spike was found, one
that was distinguishable from other spikes, we began recording. This strategy
was somewhat randomized and avoided the bias of data sampling. To our
surprise, in contrast to the cord dorsum potential data, the responses of
single dorsal horn neuron to peripheral mechanical innocuous and noxious
stimuli were significantly increased in neonatally treated rats. This
significant increase mainly occurred on the ipsilateral side of the spinal
cord in rats that received a neonatal CFA injection about 8 wk prior to
recording. However, contralateral changes were also observed in background
activity and in the response to noxious stimulation in WDR neurons. Further
analysis of the data revealed that WDR neurons displayed increased background
activity and responses to brush and pinch, suggesting that they are involved
in spontaneous pain, mechanical allodynia, and mechanical hyperalgesia as a
long-term effect of inflammation. While there was no significant increase in
background activity in HT and LT neurons, WDR neurons were the only category
involved in spontaneous pain. Ipsilateral HT neurons showed an increase in
response to noxious stimulation but no difference in response following
innocuous stimulation, suggesting that HT neurons are involved in mechanical
hyperalgesia, but not mechanical allodynia. Ipsilateral LT neurons displayed
increased responses to both innocuous and noxious stimuli, suggesting that
they are involved in both mechanical allodynia and mechanical hyperalgesia.
The significant increase was only observed at 49°C in the neonatally
treated group, suggesting a thermal hyperalgesia. This finding can be
explained by both peripheral and central mechanisms. It is known that
inflammation increases the sensitivity of the peripheral terminals of
A- and C-fibers at the site of inflammation. Additionally, inflammation
increases the excitability of spinal cord neurons
(Torebjork et al. 1992;
Woolf and Wall 1983), which
amplify all sensory inputs, including normally innocuous tactile stimuli that
are conveyed by LT A--fibers (Ma and
Woolf 1996). It has also been shown in the turpentine inflammatory
model that the amount of substance P and expression of preprotachykinin-A mRNA
in DRG cells increases significantly ipsilaterally and contralaterally 48 h
following inflammation (Neumann et al.
1996). In a neonatal model similar to ours
(Cleland et al. 1999), thermal
hyperalgesia was found on the ipsilateral side following a neonatal CFA
injection. The question that addresses the reason for increased activity on
the contralateral side is interesting and needs further investigation.
Spinal neurons are subject to marked use- or activity-dependent synaptic
plasticity. Several lines of evidence suggest that low-frequency repetitive
nociceptor input or peripheral tissue damage leads to functional changes in
the spinal cord. These changes include increased responsiveness to
suprathreshold inputs, expansion of receptive field size, reduction in
threshold, and prolonged afterdischarges
(Coderre and Melzack 1992;
Cook et al. 1987;
Dickenson and Sullivan 1987;
Dougherty and Willis 1992;
Haley et al. 1990;
Hylden et al. 1989;
Neugebauer et al. 1993;
Simone et al. 1991;
Woolf 1983;
Woolf and King 1990;
Woolf and Wall 1986;
Woolf et al. 1994). Conditions
of tissue or nerve injury often induce persistent pain, a phenomenon of
central sensitization, which can last for several days or months
(Coderre et al. 1993;
Dubner and Ruda 1992;
Woolf 1989). It is possible
that a strong persistent peripheral input induced by a CFA injection will lead
to anatomical and functional changes in the dorsal horn.
Conclusions
Electrophysiological observations of increased background activity and responses to innocuous and noxious mechanical stimulation supports the anatomical observation of increased afferent input to the lumbosacral cord of rats that were neonatally exposed to persistent inflammatory stimulation. These data further support the notion of anatomical and physiological plasticity changes in the spinal cord dorsal horn following long-term persistent inflammation.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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This study was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research.
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FOOTNOTES |
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Address for reprint requests: Y. B. Peng, Assistant Professor, Department of Psychology, P.O. Box 19528, University of Texas at Arlington, 501 S. Nedderman Drive, Arlington, TX 76019-0528 (E-mail: ypeng{at}uta.edu).
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