scholarly journals A P2X Receptor-Mediated Nociceptive Afferent Pathway to Lamina I of the Spinal Cord

2005 ◽  
Vol 1 ◽  
pp. 1744-8069-1-4 ◽  
Author(s):  
Meng Chen ◽  
Jianguo G Gu
Keyword(s):  
Spinal Cord ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Afferent Pathway ◽  
Nociceptive Transmission ◽  
Lamina I ◽  
Afferent Fibers ◽  
Nociceptive Afferents ◽  
Synaptic Effects

Of the six lamina regions in the dorsal horn of the spinal cord, lamina I is a major sensory region involved in nociceptive transmission under both physiological and pathological conditions. While P2X receptors have been shown to be involved in nociception, it remains unknown if P2X receptors are involved in nociceptive transmission to lamina I neurons. Using rat spinal cord slice preparations and patch-clamp recordings, we have demonstrated that the excitatory synaptic transmission between primary afferent fibers and lamina I neurons is significantly affected by ATP and α,β-methylene-ATP. The synaptic effects of them include the increases of the frequency of both miniature excitatory postsynaptic currents (mEPSCs) and spontaneous EPSCs (sEPSCs), and decreases of evoked EPSCs (eEPSCs). These effects were blocked by pyridoxalphosphate-6-azophenyl-2′, 4′-disulfonic acid (PPADS, 10 μM) and suramin (30 μM). In the neurons for which ATP and α,β-methylene-ATP had effects on mEPSCs, sEPSCs and eEPSCs, capsaicin produced similar synaptic effects. Our results indicate that P2X receptors are expressed on many afferent fibers that directly synapse to lamina I neurons. Furthermore, these P2X receptor-expressing afferent fibers are capsaicin-sensitive nociceptive afferents. Thus, this study reveals a P2X receptor-mediated nociceptive afferent pathway to lamina I of the spinal cord and provides a new insight into the nociceptive functions of P2X receptors.

scholarly journals Spinal P2X receptor modulates muscle pressor reflex via glutamate

2009 ◽  
Vol 106 (3) ◽  
pp. 865-870 ◽  
Author(s):  
Jianhua Li ◽  
Jian Lu ◽  
Zhaohui Gao ◽  
Satoshi Koba ◽  
Jihong Xing ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Pressor Reflex ◽  
Stimulation Of

Static contraction of skeletal muscle evokes reflex increases in blood pressure and heart rate. Previous studies showed that P2X receptors located at the dorsal horn of the spinal cord play a role in modulating the muscle pressor reflex. P2X stimulation can alter release of the excitatory amino acid, glutamate (Glu). In this report, we tested the hypothesis that stimulation of P2X receptors enhances the concentrations of Glu ([Glu]) in the dorsal horn, and that blocking P2X receptors attenuates contraction-induced Glu increases and the resultant reflex pressor response. Contraction was elicited by electrical stimulation of the L7 and S1 ventral roots of 14 cats. Glu samples were collected from microdialysis probes inserted in the L7 level of the dorsal horn of the spinal cord, and dialysate [Glu] was determined using the HPLC method. First, microdialyzing α,β-methylene ATP (0.4 mM) into the dorsal horn significantly increased [Glu]. In addition, contraction elevated [Glu] from baseline of 536 ± 53 to 1,179 ± 192 nM ( P < 0.05 vs. baseline), and mean arterial pressure by 39 ± 8 mmHg in the control experiment. Microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (10 mM) into the dorsal horn attenuated the contraction induced-Glu increase (610 ± 128 to 759 ± 147 nM; P > 0.05) and pressor response (16 ± 3 mmHg, P < 0.05 vs. control). Our findings demonstrate that P2X modulates the cardiovascular responses to static muscle contraction by affecting the release of Glu in the dorsal horn of the spinal cord.

scholarly journals Cloning and characterization of a functional P2X receptor from larval bullfrog skin

2001 ◽  
Vol 281 (3) ◽  
pp. C954-C962 ◽  
Author(s):  
Philip J. Jensik ◽  
Doyle Holbird ◽  
Michael W. Collard ◽  
Thomas C. Cox
Keyword(s):  
Pyridoxal Phosphate ◽  
Rana Catesbeiana ◽  
Short Circuit ◽  
Short Circuit Current ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Acid Protein ◽  
Sensory Reception ◽  
Tadpole Skin

ATP activates an apical-to-basolateral nonselective cation current across the skin of larval bullfrogs ( Rana catesbeiana) with similarities to currents carried by some P2X receptors. A functional P2X receptor was cloned from tadpole skin RNA that encodes a 409-amino acid protein with highest protein homology to cP2X8. RT-PCR showed that this transcript was found in skin, heart, eye, brain, and skeletal muscle of tadpoles but not in skin, brain, or heart of adults. After transcribed RNA from this clone was injected into Xenopus oocytes, application of ATP activated a transient current similar to other P2X receptors and the ATP-activated transient in short-circuit current ( I sc) across intact skin. The agonists 2-methylthio-ATP and adenosine-5′- O-(thiotriphoshate) also activated transient currents. α,β-Methylene-ATP and ADP were poor agonists of this receptor. Suramin and pyridoxal phosphate 6-azophenyl-2′,4′-disulfonic acid tetrasodium (PPADS) were potent antagonists, and PPADS showed an irreversible blockade of this receptor to agonist activation. Under external Na+-free, Ca2+/Mg2+-free conditions ( N-methyl-d-glucamine replacement, 0.5 mM EGTA), ATP activated a steadily increasing inward current. Fluorescence microscopy showed that propidium was entering the cells, suggesting that a relatively large pore size was formed under zero divalent conditions. This clone has some characteristics consistent with previously described ATP-activated I sc in the tadpole skin. Because the clone is not found in adult skin, it may have some exclusive role in the tadpole such as sensory reception by the skin or triggering apoptosis at metamorphosis.

scholarly journals Involvement of Peripheral Purinoceptors in Sympathetic Modulation of Capsaicin-Induced Sensitization of Primary Afferent Fibers

2006 ◽  
Vol 96 (5) ◽  
pp. 2207-2216 ◽  
Author(s):  
Yong Ren ◽  
Xiaoju Zou ◽  
Li Fang ◽  
Qing Lin
Keyword(s):  
Receptor Agonist ◽  
P2x Receptors ◽  
Intradermal Injection ◽  
Disulfonic Acid ◽  
Mechanical Stimuli ◽  
Primary Afferent ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sympathetic Modulation ◽  
Primary Afferent Fibers

Purinoceptors are distributed in primary afferent terminals, where transmission of nociceptive information is modulated by these receptors. In the present study, we evaluated whether the activation or blockade of purinoceptors of subtypes P2X and P2Y in the periphery affected the sensitization of primary afferents induced by intradermal injection of capsaicin (CAP) and examined their role in sympathetic modulation of sensitization of primary nociceptive afferents. Afferent activity was recorded from single Aδ- and C-primary afferent fibers in the tibial nerve in anesthetized rats. Peripheral pretreatment with α,β-methylene adenosine 5′-triphosphate (α,β-meATP), a P2X-selective receptor agonist, could potentiate the CAP-induced enhancement of responses of Aδ- and C-primary afferent nociceptive fibers to mechanical stimuli in sympathetically intact rats. After sympathetic denervation, the enhanced responses of both Aδ- and C-fibers after CAP injection were dramatically reduced. However, this reduction could be restored when P2X receptors were activated by α,β-meATP. A blockade of P2X receptors by pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid could significantly reduce the CAP-induced sensitization of Aδ- and C-fibers. Pretreatment with uridine 5′-triphosphate, a P2Y-selective receptor agonist, did not significantly affect or restore the CAP-induced sensitization of Aδ- and C-fibers under sympathetically intact or sympathectomized conditions. Our study supports the view that ATP plays a role in modulation of primary afferent nociceptor sensitivity mainly by P2X receptors. Combined with our previous study, our data also provide further evidence that the sensitization of primary afferent nociceptors is subject to sympathetic modulation by activation of P2X as well as α1-adrenergic receptors.

Distinct Roles of P2X Receptors in Modulating Glutamate Release at Different Primary Sensory Synapses in Rat Spinal Cord

2003 ◽  
Vol 89 (6) ◽  
pp. 3243-3252 ◽  
Author(s):  
Terumasa Nakatsuka ◽  
Kenzo Tsuzuki ◽  
Jennifer X. Ling ◽  
Hideki Sonobe ◽  
Jianguo G. Gu
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Glutamate Release ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Surgical Removal ◽  
Receptor Subtypes ◽  
Isolectin B4 ◽  
Subtype Selective ◽  
Afferent Terminals

Using spinal cord slice preparations and patch-clamp recordings in lamina II and lamina V regions, we tested a hypothesis that P2X receptor subtypes differentially modulate glutamate release from primary afferent terminals innervating different sensory regions. We found that activation of P2X receptors by α,β-methylene-ATP increased glutamate release onto >80% of DH neurons in both lamina regions. However, two distinct types of modulation, a transient and a long-lasting enhancement of glutamate release were observed. In lamina II recordings, >70% of the modulation was transient. In contrast, P2X receptor-mediated modulation was always long-lasting in lamina V. Pharmacologically, both transient and long-lasting types of modulation were blocked by 10 μM pyridxal-phospahte-6-azophenyl-2′,4′-disulphonic acid tetrasodium, a broad-spectrum P2X receptor antagonist. Transient modulation was not observed in the presence of 1 μM trinitrophenyl-ATP (TNP-ATP), a subtype-selective P2X receptor antagonist, suggesting that homomeric P2X3 receptors may be involved in the transient modulation in lamina II. The long-lasting modulation remained in the presence of 1 μM TNP-ATP. Selective removal of P2X3-expressing afferent terminals by the targeting toxin saporin-conjugated isolectin B4 or surgical removal of superficial DH did not affect P2X receptor-mediated long-lasting modulation in lamina V. Taken together, these results suggest that P2X receptor subtypes play distinct roles in sensory processing in functionally different sensory regions.

TNP-ATP-Resistant P2X Ionic Current on the Central Terminals and Somata of Rat Primary Sensory Neurons

2003 ◽  
Vol 89 (6) ◽  
pp. 3235-3242 ◽  
Author(s):  
Kenzo Tsuzuki ◽  
Ariel Ase ◽  
Philippe Séguéla ◽  
Terumasa Nakatsuka ◽  
Cong-Yi Wang ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Ionic Current ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Receptor Subtypes ◽  
Sensory Transmission ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Disulphonic Acid ◽  
Potent Antagonist

P2X receptors have been suggested to be expressed on the central terminals of Aδ-afferent fibers innervating dorsal horn lamina V and play a role in modulating sensory synaptic transmission. These P2X receptors have been widely thought to be P2X2+3 receptors. However, we have recently found that P2X receptor-mediated modulation of sensory transmission in lamina V is not inhibited by trinitrophenyl-adenosine triphosphate (TNP-ATP), a potent antagonist of P2X1, P2X3 homomers, and P2X2+3 heteromers. To provide direct evidence for the presence of TNP-ATP-resistant P2X receptors on primary afferent fibers, we examined α,β-methylene-ATP (αβmeATP)-evoked currents and their sensitivity to TNP-ATP in rat dorsal root ganglion (DRG) neurons. αβmeATP evoked fast currents, slow currents, and mixed currents that contained both fast and slow current-components. Fast currents and fast current components in the mixed currents were both completely inhibited by 0.1 μM TNP-ATP ( n = 14). Both slow currents and slow-current components in the mixed currents showed broad spectrum of sensitivity to 1 μM TNP-ATP, ranging from complete block (TNP-ATP-sensitive) to little block (TNP-ATP-resistant). TNP-ATP-resistant currents evoked by 10 μM αβmeATP could be largely inhibited by 10 μM iso-pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid. Cells with P2X currents that were highly resistant to TNP-ATP were found to be insensitive to capsaicin. These results suggest that TNP-ATP-resistant P2X receptor subtypes are expressed on capsaicin-insensitive Aδ-afferent fibers and play a role in modulating sensory transmission to lamina V neurons.

ATP stimulates chemically sensitive and sensitizes mechanically sensitive afferents

2002 ◽  
Vol 283 (6) ◽  
pp. H2636-H2643 ◽  
Author(s):  
Jianhua Li ◽  
Lawrence I. Sinoway
Keyword(s):  
Blood Pressure ◽  
Receptor Antagonist ◽  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
P2x Receptors ◽  
Triceps Surae ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Muscle Stretch ◽  
Arterial Blood

We examined whether ATP stimulation of P2X purinoceptors would raise blood pressure in decerebrate cats. Femoral arterial injection of the P2X receptor agonist α,β-methylene ATP into the blood supply of the triceps surae muscle induced a dose-dependent increase in arterial blood pressure. The maximal increase in mean arterial pressure (MAP) evoked by 0.1, 0.2, and 0.5 mM α,β-methylene ATP (0.5 ml/min injection rate) was 6.2 ± 2.5, 22.5 ± 4.4, and 35.2 ± 3.9 mmHg, respectively. The P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (2 mM ia) attenuated the increase in MAP elicited by intra-arterial α,β-methylene ATP (0.5 mM), whereas the P2Y receptor antagonist reactive blue 2 (2 mM ia) did not affect the MAP response to α,β-methylene ATP. In a second group of experiments, we tested the hypothesis that ATP acting through P2X receptors would sensitize muscle afferents and, thereby, augment the blood pressure response to muscle stretch. Two kilograms of muscle stretch evoked a 26.5 ± 4.3 mmHg increase in MAP. This MAP response was enhanced when 2 mM ATP or 0.1 mM α,β-methylene ATP (0.5 ml/min) was arterially infused 10 min before muscle stretch. Furthermore, this effect of ATP on the pressor response to stretch was attenuated by 2 mM pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid ( P < 0.05) but not by the P1 purinoceptor antagonist 8-( p-sulfophenyl)-theophylline (2 mM). These data indicate that activation of ATP-sensitive P2X receptors evokes a skeletal muscle afferent-mediated pressor response and that ATP at relatively low doses enhances the muscle pressor response to stretch via engagement of P2X receptors.

scholarly journals Temporal and Spatial Profiles of Pontine-Evoked Monoamine Release in the Rat's Spinal Cord

2003 ◽  
Vol 89 (6) ◽  
pp. 2943-2951 ◽  
Author(s):  
Ian D. Hentall ◽  
Riza Mesigil ◽  
Alberto Pinzon ◽  
Brian R. Noga
Keyword(s):  
Spinal Cord ◽  
Peak Level ◽  
Locus Ceruleus ◽  
Spatial And Temporal Patterns ◽  
Spatiotemporal Resolution ◽  
Locomotor Rhythm ◽  
Nociceptive Transmission ◽  
Carbon Fiber Microelectrode ◽  
Lamina I ◽  
Decay Times

In the spinal cord, the monoamine neurotransmitter norepinephrine, which is released mainly from fibers descending from the dorsal pons, has major modulatory effects on nociception and locomotor rhythms. To map the spatial and temporal patterns of this release, changes in monoamine level were examined in laminae I–VIII of lumbar segments L3–L6 of halothane-anesthetized rats during pontine stimulation. The changes were measured through a carbon fiber microelectrode at 0.5-s intervals by fast cyclic voltammetry, which presently is the method of best spatiotemporal resolution. When different pontine sites were tested with 20-s pulse trains (50-to 200-μA amplitude, 0.5-ms pulse width, and 50-Hz frequency) during measurement in the dorsal horn (lamina IV), the largest consistent increases were produced by the locus ceruleus, although effective pontine sites extended 1.5 mm dorsally and ventral from the locus ceruleus. When the locus ceruleus stimulus was used to map the spinal cord, increased levels were always seen in lamina I and laminae IV–VIII, whereas 50% of sites in laminae II and III showed substantial decreases and the rest showed increases. These increases typically had short latencies [4.5 ± 0.4 (SE) s] and variable decay times (5–200 s), with peaks occurring during the stimulus train (mean rise-time: 12.0 ± 0.6 s). The mean peak level was 544 ± 82 nM as estimated from postexperimental calibration with norepinephrine. Other significant laminar differences included higher mean peak concentrations (805 nM) and rise times (14.9 s) in lamina I and shorter latencies in lamina VI (3.2 s). Peak concentrations were inversely correlated with latency. When stimulation frequency was varied, increases were disproportionately larger with faster frequencies (≥50 Hz), hence extrajunctional overflow probably contributed most of the signal. We conclude, generally, that pontine noradrenergic control is exerted on widespread spinal laminae with a significant component of paracrine transmission after several seconds of sustained activity. Relatively stronger effects prevail where nociceptive transmission (lamina I) and locomotor rhythm generation (lamina VI) occur.

scholarly journals Purinergic 2X receptors play a role in evoking the exercise pressor reflex in rats with peripheral artery insufficiency

2014 ◽  
Vol 306 (3) ◽  
pp. H396-H404 ◽  
Author(s):  
Audrey J. Stone ◽  
Katsuya Yamauchi ◽  
Marc P. Kaufman
Keyword(s):  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Femoral Arteries ◽  
Exercise Pressor Reflex ◽  
Pressor Responses ◽  
Before And After ◽  
Pressor Reflex

Purinergic 2X (P2X) receptors on the endings of thin fiber afferents have been shown to play a role in evoking the exercise pressor reflex in cats. In this study, we attempted to extend this finding to decerebrated, unanesthetized rats whose femoral arteries were either freely perfused or were ligated 72 h before the start of the experiment. We first established that our dose of pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS; 10 mg/kg), a P2X receptor antagonist, attenuated the pressor response to α,β-methylene ATP (10 μg/kg), a P2X receptor agonist. We then compared the exercise pressor reflex before and after infusing PPADS into the arterial supply of the hindlimb muscles that were statically contracted. In rats with freely perfused femoral arteries, the peak pressor responses to contraction were not significantly attenuated by PPADS (before PPADS: 19 ± 2 mmHg, 13 min after PPADS: 17 ± 2 mmHg, and 25 min after PPADS: 17 ± 3 mmHg). Likewise, the cardioaccelerator and renal sympathetic nerve responses were not significantly attenuated. In contrast, we found that in rats whose femoral arteries were ligated PPADS significantly attenuated the peak pressor responses to contraction (before PPADS: 37 ± 5 mmHg, 13 min after PPADS: 27 ± 6 mmHg, and 25 min after PPADS: 25 ± 5 mmHg; P < 0.05). Heart rate was not significantly attenuated, but renal SNA was at certain time points over the 30-s contraction period. We conclude that P2X receptors play a substantial role in evoking the exercise pressor reflex in rats whose femoral arteries were ligated but play only a minimal role in evoking the reflex in rats whose femoral arteries were freely perfused.

Primary Afferent Fibers That Contribute to Increased Substance P Receptor Internalization in the Spinal Cord After Injury

1999 ◽  
Vol 81 (3) ◽  
pp. 1379-1390 ◽  
Author(s):  
Brian J. Allen ◽  
Jun Li ◽  
Patrick M. Menning ◽  
Scott D. Rogers ◽  
Joseph Ghilardi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Nerve Transection ◽  
Primary Afferent ◽  
Lamina I ◽  
C Fibers ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Stimulation Of

Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury. Upon noxious stimulation, substance P (SP) is released from primary afferent fibers into the spinal cord where it interacts with the SP receptor (SPR). The SPR is located throughout the dorsal horn and undergoes endocytosis after agonist binding, which provides a spatial image of SPR-containing neurons that undergo agonist interaction. Under normal conditions, SPR internalization occurs only in SPR+ cell bodies and dendrites in the superficial dorsal horn after noxious stimulation. After nerve transection and inflammation, SPR immunoreactivity increases, and both noxious as well as nonnoxious stimulation produces SPR internalization in the superficial and deep dorsal horn. We investigated the primary afferent fibers that contribute to enhanced SPR internalization in the spinal cord after nerve transection and inflammation. Internalization evoked by electrical stimulation of the sciatic nerve was examined in untreated animals, at 14 days after sciatic nerve transection or sham surgery and at 3 days after hindpaw inflammation. Electrical stimulation was delivered at intensities to excite Aβ fibers only, Aβ and Aδ fibers or A and C fibers as determined by the compound action potential recorded from the tibial nerve. Electrical stimuli were delivered at a constant rate of 10 Hz for a duration of 5 min. Transection of the sciatic nerve and inflammation produced a 33.7 and 32.5% increase in SPR and immunoreactivity in lamina I, respectively. Under normal conditions, stimulation of Aδ or C fibers evoked internalization that was confined to the superficial dorsal horn. After transection or inflammation, there was a 20–24% increase in the proportion of SPR+ lamina I neurons that exhibited internalization evoked by stimulation of Aδ fibers. The proportion of lamina I SPR+ neurons that exhibited internalization after stimulation of C-fibers was not altered by transection or inflammation because this was nearly maximal under normal conditions. Moreover, electrical stimulation sufficient to excite C fibers evoked SPR internalization in 22% of SPR+ lamina III neurons after nerve transection and in 32–36% of SPR+ neurons in lamina III and IV after inflammation. Stimulation of Aβ fibers alone never evoked internalization in the superficial or deep dorsal horn. These results indicate that activation of small-caliber afferent fibers contributes to the enhanced SPR internalization in the spinal cord after nerve transection and inflammation and suggest that recruitment of neurons that possess the SPR contributes to hyperalgesia.

Spinal P2X receptor modulates reflex pressor response to activation of muscle afferents

2005 ◽  
Vol 288 (5) ◽  
pp. H2238-H2243 ◽  
Author(s):  
Zhaohui Gao ◽  
Valerie Kehoe ◽  
Lawrence I. Sinoway ◽  
Jianhua Li
Keyword(s):  
Dorsal Horn ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
P2x Receptors ◽  
Muscle Afferents ◽  
P2x Receptor ◽  
Reflex Response ◽  
Disulfonic Acid ◽  
Synaptic Site ◽  
Stimulation Of

Static contraction of skeletal muscle evokes increases in blood pressure and heart rate. Previous studies suggested that the dorsal horn of the spinal cord is the first synaptic site responsible for those cardiovascular responses. In this study, we examined the role of ATP-sensitive P2X receptors in the cardiovascular responses to contraction by microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) into the L7 level of the dorsal horn of nine anesthetized cats. Contraction was elicited by electrical stimulation of the L7 and S1 ventral roots. Blockade of P2X receptor attenuated the contraction induced-pressor response [change in mean arterial pressure (ΔMAP): 16 ± 4 mmHg after 10 mM PPADS vs. 42 ± 8 mmHg in control; P < 0.05]. In addition, the pressor response to muscle stretch was also blunted by PPADS (ΔMAP: 27 ± 5 mmHg after PPADS vs. 49 ± 8 mmHg in control; P < 0.05). Finally, activation of P2X receptor by microdialyzing 0.5 mM α,β-methylene into the dorsal horn significantly augmented the pressor response to contraction. This effect was antagonized by prior PPADS dialysis. These data demonstrate that blockade of P2X receptors in the dorsal horn attenuates the pressor response to activation of muscle afferents and that stimulation of P2X receptors enhances the reflex response, indicating that P2X receptors play a role in mediating the muscle pressor reflex at the first synaptic site of this reflex.

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