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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal cord injury (SCI) results in abnormal pain syndromes in humans. In a rodent model of SCI, T13 spinal hemisection results in allodynia and hyperalgesia due in part to interruption of descending pathways, including serotonergic (5-HT) systems, that leads to hyperexcitability of dorsal horn neurons. To characterize further the role of 5-HT and 5-HT receptor subtypes 5-HT(1A) and 5-HT(3) in neuronal activation after hemisection, we have examined the responsiveness of dorsal horn neurons to a variety of innocuous and noxious peripheral stimuli. Male Sprague-Dawley rats, 150-175 g, were spinally hemisected (n=40) at T13 and allowed 4 weeks for development of mechanical allodynia and thermal hyperalgesia. Animals then underwent electrophysiologic recording and the results were compared with those from sham controls (n=15). Evoked responses of convergent dorsal horn neurons (n=224 total) at L3-L5 to innocuous and noxious peripheral stimuli were characterized after administration of vehicle, 5-HT (25, 50, 100, and 200 microg), 5-HT (100 microg) in conjunction with the selective 5-HT(1A) antagonist WAY 100135 (100 microg), the 5-HT(3) antagonist MDL 72222 (100 microg), the selective 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 150 microg), or the 5-HT(3) agonist 2-Me-5HT (75 microg), with or without pretreatment with antagonists; all treatments were delivered topically onto the cord adjacent to the recording electrode. In hemisected animals, increased responsiveness of convergent cells to all peripheral stimuli was observed bilaterally when compared to controls. No changes in ongoing background activity were present. In control animals, only the highest dose of 5-HT (200 microg) was sufficient to reduce evoked activity, whereas in hemisected animals a concentration-dependent decrease in response was observed. In hemisected animals, both 5-HT(1A) and 5-HT(3) receptor antagonism reduced the effectiveness of 5-HT, restoring elevated evoked activity by up to 70% at the doses tested. Administration of 5-HT(1A) and 5-HT(3) receptor agonists also decreased hyperexcitability, effects prevented by pretreatment with corresponding antagonists. These results demonstrate the development of denervation supersensitivity to 5-HT following SCI, corroborate behavioral studies showing the effectiveness of 5-HT in reducing allodynia and hyperalgesia after SCI, and contribute to a mechanistic understanding of the role of 5-HT receptor subtypes in chronic central pain.
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PMID:Serotonin receptors 5-HT1A and 5-HT3 reduce hyperexcitability of dorsal horn neurons after chronic spinal cord hemisection injury in rat. 1261 Jun 85

Unilateral T13 hemisection of the rat spinal cord produces a model of chronic spinal cord injury (SCI) that is characterized by bilateral hyperexcitability of lumbar dorsal horn neurons, and behavioral signs of central pain. While we have demonstrated that responsiveness of multireceptive (MR) dorsal horn neurons is dramatically increased at 28 days after injury, the effects of acute hemisection are unknown and predicted to be different than observed chronically. In the present study, the consequences of T13 hemisection are examined acutely at 45 min in MR neurons both ipsilateral and contralateral to the site of injury, and compared to the same class of cells at 28 days after injury (n=20 cells total per group: 2-3 cells/side of the cord from n=5 animals). Acutely, ipsilateral to the hemisection, both spontaneous and evoked activity of MR neurons were significantly increased, whereas contralaterally, only evoked activity was significantly increased. In animals 28 days after hemisection, spontaneous activity of MR neurons was comparable to intact levels ipsilaterally, and cells exhibited hyperexcitability to evoked stimuli bilaterally. Expansion of cutaneous receptive fields was observed only in hindpaws ipsilateral to the lesion, acutely. These results demonstrate dynamic plasticity in properties of dorsal horn somatosensory neurons after SCI.
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PMID:Temporal plasticity of dorsal horn somatosensory neurons after acute and chronic spinal cord hemisection in rat. 1270 67

Among the numerous pain control mechanisms that have been proposed, those acting at the spinal cord have been broadly studied, but little is known about how neuropeptides originating in supraspinal structures may relate to pain and analgesic mechanisms. Oxytocin (OT), in addition to its well known hormonal action, produces neuronal effects in various regions of the central nervous system. Indeed, some parvocellular neurons in the hypothalamic paraventricular nucleus (PVN) are oxytocinergic and project to the caudal part of the brain and the spinal cord. Moreover, the rat spinal cord shows a good overlap between the oxytocinergic hypothalamo-spinal neuron projections and the distribution of OT binding sites. However, the physiological significance of these binding sites is largely unknown. Extracellular unit activity of spinal cord neurons was recorded at the T13-L1 levels in male rats anesthetized with halotane. Somatic stimulation was applied to the inner and outer thigh of the ipsilateral hindpaw, and glutamate (GLU) and OT were locally delivered by pressure using pipettes coupled to recording electrodes. Our results show that spinal cord neurons, mainly located in the dorsal horn, in the intermediolateral cell column (IML) and in the intermediomedial gray matter (IMM), respond to the application of OT (71.5%) with activation (48%) or inhibition (52%). In some cases, opposite OT effects were observed during simultaneous recordings of two cells, suggesting OT activation of an inhibitory interneuron followed by the inhibition of the second recorded neuron. Increases in neuronal firing rate produced by GLU could be blocked by prior OT application. Finally, OT could reduce or partially block the responses to tactile and nociceptive somatic stimulation. We found that spinal cord neurons are sensitive to OT indicating that OT binding sites are functionally active. OT effects suggest the activation of inhibitory interneurons acting on a second order projecting cells to modulate afferent tactile and nociceptive information.
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PMID:Actions of oxytocin and interactions with glutamate on spontaneous and evoked dorsal spinal cord neuronal activities. 1276 24

We examined whether morphine reduced the behavioral signs of neuropathic pain below level induced by T13 spinal hemisection in rats. In order to examine the effect of morphine on the mechanical allodynia, morphine alone, morphine with naloxone and saline were administered intraperitoneally and intrathecally and behavioral tests were conducted. In systemic injection, mechanical allodynia was reduced only when a higher concentration of morphine (5 mg/kg) was used. Intrathecally injected morphine (0.5, 1, 2, 5 microg) reduced mechanical allodynia dose-dependently. It is suggested that systemic morphine has limited effect on mechanical allodynia but direct spinal administration of morphine is more effective in controlling central pain following spinal cord injury.
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PMID:Effects of morphine on mechanical allodynia in a rat model of central neuropathic pain. 1280 94

The P2X(3) receptor is normally localized in a sub-population of small-diameter dorsal root ganglion (DRG) neurons, and is thought to be related to pain perception. The aim of this study in rats was to examine P2X(3)-immunoreactivity in DRG neurons innervating the lumbar disc and in DRG neurons innervating cutaneous tissues. Fluoro-Gold was applied to the L5-L6 disc, the plantar skin of the hind paw (L4-L5 dermatomes), and the back skin (L1-L2 dermatomes). It has been reported that the L5-L6 disc is innervated by T13-L5 DRG neurons. We performed immunostaining using antibodies against the P2X(3) receptor of T13-L5 DRGs to examine the L5-L6 disc, L4 and L5 DRGs to examine plantar skin and L1 and L2 DRGs to examine back skin. The P2X(3)-immunoreactivity was detected in 22.0 and 22.8% of neurons, labeled by Fluoro-Gold applied to plantar and back skin, respectively. However, P2X(3)-immunoreactivity was detected in only 4.0% of the neurons projecting to the L5-L6 disc. The proportion of P2X(3)-immunoreactive neurons was significantly larger in the DRG neurons innervating the plantar or the back skin, than in the DRG neurons innervating the lumbar disc. These results suggest that the P2X(3) receptors are abundant in DRG neurons innervating cutaneous tissues, but not in neurons innervating the lumbar disc. It is likely therefore that the P2X(3) receptor is less related to the mechanism of discogenic pain, than to cutaneous tissue pain.
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PMID:P2X3-immunoreactive primary sensory neurons innervating lumbar intervertebral disc in rats. 1455 43

Spinal lamina I neurons expressing the substance P receptor (SPR) have been shown to play a role in the transmission of somatic inflammatory and neuropathic pain. To evaluate their involvement in visceral nociception in both the noninflamed and inflamed colon, we examined the expression and ligand-induced internalization of the SPR in the rat spinal cord after distention of the noninflamed colon and in rats with inflammation induced by intracolonic instillation of zymosan (3 hours). In the noninflamed animal, acute noxious but not non-noxious colorectal distention induced SPR internalization in lamina I neurons at the thoracolumbar (T13) and lumbosacral (S1) spinal levels, whereas SPR internalization was not detected in lamina I neurons at spinal lumbar segment L4. Although zymosan-induced colorectal inflammation alone did not induce SPR internalization in lamina I neurons, there was an increased number of SPR-expressing lamina I neurons showing SPR internalization in segments T12 through S2 of the spinal cord after colorectal distention. These results show that acute noxious visceral stimuli induce activation of spinal lamina I neurons expressing the SPR and, that after visceral inflammation, there is a marked increase in both the number and rostrocaudal extent of lamina I SPR neurons activated in response to both normally non-noxious and noxious distention of the colon.
J Pain 2002 Feb
PMID:Activation of lamina I spinal cord neurons that express the substance P receptor in visceral nociception and hyperalgesia. 1462 48

Mechanical and thermal allodynia develops after spinal cord injury in three areas relative to the lesion: below level, at level, and above level. The present study tests colocalization of CGRP, associated with nociceptive neurons, with growth-associated protein (GAP-43), expressed in growing neurites, to test for neurite sprouting as a mechanism for reorganization of pain pathways at the level of the lesion and distant segments. Male Sprague-Dawley rats were divided into three groups: sham control (N = 10), hemisected at T13 and sacrificed at 3 days (N = 5) and at 30 days (N = 5) following surgery, the spinal cord tissue was prepared for standard fluorescent immunocytochemistry using mouse monoclonal anti-GAP-43 (1:200) and/or rabbit polyclonal anti-CGRP (1:200), density of immunoreaction product (IR) was quantified using the Bioquant software and values from the hemisected group were compared to similar regions from the sham control. We report significant increases at C8 and L5, in CGRP-IR in lamina III compared to control tissue (P < 0.05). We report significant bilateral increases in GAP-43-IR at C8, T13, and L5 segments in lamina I through IV, at 3 days post hemisection, compared to control tissue (P < 0.05), some of which is colocalized with alpha-CGRP. The increased area and density of GAP-43-IR is consistent with neurite sprouting, and the colocalization with alpha-CGRP indicates that some of the sprouting neurites are nociceptive primary afferents. These data are consistent with endogenous regenerative neurite growth mechanisms that occur near and several segments from a spinal lesion, that provide one of many substrates for the development and maintenance of the dysfunctional state of allodynia after spinal cord injury.
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PMID:Direct evidence of primary afferent sprouting in distant segments following spinal cord injury in the rat: colocalization of GAP-43 and CGRP. 1463 7

Neuropathic pain after spinal cord injury (SCI) represents a difficult problem that is commonly refractory to conventional medical management. To determine if spinal release of gamma-amino butyric acid (GABA) could reduce below-level central neuropathic pain after SCI, we constructed a replication-incompetent herpes simplex virus (HSV)-based vector encoding one isoform of human glutamic acid decarboxylase (GAD67). Dorsal root ganglion (DRG) neurons transduced in vitro or in vivo by subcutaneous inoculation produced GAD and released GABA constitutively. T13 spinal cord hemisection resulted in central neuropathic pain manifested by mechanical allodynia and thermal hyperalgesia. Subcutaneous inoculation of the vector into both feet reduced both manifestations of below-level SCI pain; the vector-mediated effect was partially reversed by intrathecal bicuculline or phaclofen at doses that did not affect thresholds in normal or injured uninoculated animals. Vector-mediated GABA release attenuated the increase in spinal calcitonin gene-related peptide immunoreactivity caused by cord hemisection. These results suggest that HSV-mediated gene transfer to DRG could be used to treat below-level central neuropathic pain after incomplete SCI.
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PMID:Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain. 1523 42

Spinal cord injury (SCI) often leads to chronic central pain (CCP) syndromes such as allodynia and hyperalgesia. Although several experimental animal models for CCP studies exist, little is known about the effect of age on the development of CCP following SCI. In this study, we evaluated behavioral responses to mechanical and thermal stimuli following SCI using three different age groups of adult Sprague-Dawley rats: young (40 days), adult (60 days), and middle-age (12 months). SCI was produced by unilateral hemisection of the spinal cord at T13. Behavioral measures of locomotor function were assayed in open field tests and somatosensory function by paw withdrawal frequency (PWF) to innocuous mechanical stimuli and paw withdrawal latency (PWL) to radiant heat stimuli on both the forelimbs and hindlimbs. Prior to hemisection, the PWF was not different between the three groups; however, the PWL of the young group was significantly greater than the adult and middle-age group. After spinal hemisection, spontaneous locomotor recovery occurred more rapidly in young and adult than in middle-age rats. In both forelimbs and hindlimbs, the young group displayed a significant increase in PWF and a significant decrease in PWL compared to presurgical and sham values or values from the adult and middle-age groups. These results indicate that younger rats developed more robust neuropathic behaviors than middle-age rats, indicating that age selection is an important factor in animal models of CCP syndromes following SCI. Additionally, our data suggest that age at the time of injury may be one risk factor in predicting the development of CCP after SCI in people.
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PMID:Effect of age at time of spinal cord injury on behavioral outcomes in rat. 1531 98

The dorsal column-medial lemniscal (DC-ML) system is known to be a route of ascending input signals for mechanical allodynia following peripheral nerve injury. We examined whether the pain signals after spinal hemisection were transmitted via the DC-ML system in the induction and maintenance phases of the neuropathic pain. Under enflurane anesthesia, rats were subjected to spinal hemisection at T13 level and bilateral DC lesion was made at T8 level 1 day or 3 weeks after the hemisection. The DC lesion 1 day after the hemisection significantly reduced the mechanical, but not cold, allodynia, whereas the DC lesion 3 weeks after the hemisection did not change both mechanical and cold allodynia. These results suggest that the signals for mechanical allodynia following spinal hemisection should be transmitted via the DC-ML system in the induction, but not maintenance, phase.
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PMID:Dorsal column lesion reduces mechanical allodynia in the induction, but not the maintenance, phase in spinal hemisected rats. 1584 67


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