Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain originating from the hip may be referred to the groin and anterior thigh. We investigated sensory dorsal root ganglion neurons innervating the hip and the inguinal skin in rats using retrograde neurotransport and immunohistochemistry. A retrograde neurotracer Fluoro-Gold was injected into the left hip or inguinal skin of rats. Seven days later, we harvested bilateral dorsal root ganglions and counted the number of Fluoro-Gold-labeled neurons positive for calcitonin gene-related peptide, a marker of nerve growth factor-dependent neurons, or isolectin B4, a marker of glial cell line-derived neurotrophic factor-dependent neurons. In the hip group, Fluoro-Gold-labeled neurons were distributed throughout the left dorsal root ganglions from T13 to L5, primarily at L1, L2, L3, and L4, and the percentage of calcitonin gene-related peptide-positive neurons was higher than that of isolectin B4-binding neurons. In the inguinal skin group, Fluoro-Gold-labeled neurons were distributed throughout the left dorsal root ganglions from T13 to L3, primarily at L1, L2, and L3, and the percentage of isolectin B4-binding neurons was higher than that of calcitonin gene-related peptide-positive neurons. These data suggest the sensory innervation pattern and characteristics of the sensory nerve of the rat hip are different from those of inguinal skin.
 ...
PMID:Differences in innervation and innervated neurons between hip and inguinal skin. 1870 14

Central neuropathic pain is refractory to conventional treatment and thus remains a therapeutic challenge. In this work, we used a well-recognized model of central neuropathic pain to evaluate time-dependent expression of preprodynorphin (ppD), protein kinase C gamma (PKCgamma) and NMDA receptor (NMDAR) subunits NR1, NR2A and NR2B, all critical players in nociceptive processing at the spinal level. Male Sprague-Dawley rats were subjected to spinal hemisection at T13 level and sham-operated rats were included as control animals. The development of hindpaw mechanical allodynia was assessed using the von Frey filaments test. Real time RT-PCR was employed to determine the relative mRNA levels of NMDAR subunits, ppD and PKCgamma in the dorsal spinal cord 1, 14 and 28 days after injury. Our results show that, coincident with the allodynic phase after injury, there was a strong up-regulation of the mRNAs coding for ppD, PKCgamma and NMDAR subunits in the dorsal spinal cord caudal to the injury site. The present study provides further evidence that these molecules are involved in the development/maintenance of central neuropathic pain and thus could be the target of therapeutic approaches.
 ...
PMID:Neuropathic pain and temporal expression of preprodynorphin, protein kinase C and N-methyl-D-aspartate receptor subunits after spinal cord injury. 1883 24

Loss of function is usually considered the major consequence of spinal cord injury (SCI). However, pain severely compromises the quality of life in nearly 70% of SCI patients. The principal aim of this study was to assess the contribution of Tumor necrosis factor alpha (TNF-alpha) to SCI pain. TNF-alpha blockers have already been successfully used to treat inflammatory disorders but there are few studies on its effect on neuropathic pain, especially following SCI. Following T13 spinal cord hemisection, we examined the effects on mechanical allodynia and microglial activation of immediate and delayed chronic intrathecal treatment with etanercept, a fusion protein blocker of TNF-alpha. Immediate treatment (starting at the time of injury) with etanercept resulted in markedly reduced mechanical allodynia 1, 2, 3 and 4 weeks after SCI. Delayed treatment had no effect. Immediate etanercept treatment also reduced spinal microglial activation assessed by OX-42 immunostaining, a putative marker of activated microglia. To assess whether the effects of etanercept were mediated via decreased microglial activation, we examined the effects of the microglial inhibitor, minocycline which significantly reduced the development of pain behaviours at 1 and 2 weeks after SCI compared to saline treatment. Minocycline also significantly reduced microglial OX-42 expression. Furthermore, minocycline decreased the expression of noxious-stimulation-induced c-Fos, suggesting an effect on evoked neuronal activity. This study demonstrates that TNF-alpha plays an important role in the establishment of neuropathic pain following SCI, seemingly dependent on microglial activation. Pharmacological targeting of TNF-alpha may offer therapeutic opportunities for treating SCI pain.
Eur J Pain 2009 Aug
PMID:Effects of Etanercept and Minocycline in a rat model of spinal cord injury. 1884 75

We investigated the participation of cyclin-dependent kinase-5 (Cdk5)-mediated N-methyl-D-aspartate receptor (NMDAR) NR2B subunit phosphorylation in cross-organ reflex sensitization caused by colon irritation. The external urethral sphincter electromyogram (EUSE) reflex activity evoked by the pelvic afferent nerve test stimulation (TS, 1 stimulation/30s) and protein expression in the spinal cord and dorsal root ganglion tissue (T13-L2 and L6-S2 ipsilateral to the stimulation) in response to colon mustard oil (MO) instillation were tested in anesthetized rats. When compared with a baseline reflex activity with a single action potential evoked by the TS before the administration of test agents, MO instillation into the descending colon sensitized the evoked activity characterized by elongated firing in the reflex activity in association with increased protein levels of Cdk5, PSD95, and phosphorylated NR2B (pNR2B) but not of total NR2B (tNR2B) in the spinal cord tissue. Both cross-organ reflex sensitization and increments in protein expression were reversed by intra-colonic pretreatments with ruthenium red (a non-selective transient receptor potential vanilloid, TRPV, antagonist), capsaizepine (a TRPV1-selective antagonist), lidocaine (a nerve conduction blocker) as well as by the intra-thecal pretreatment with APV (a NRMDR antagonist) Co-101244 (a NR2B-selective antagonist) and roscovitine (a Cdk5 antagonist). Moreover, compared with the control group, both the increase in pNR2B and the cross-organ reflex sensitization were attenuated in the si-RNA of NR2B rats. All these results suggested that Cdk-dependent NMDAR NR2B subunit phosphorylation mediates the development of cross-organ pelvic-urethra reflex sensitization caused by acute colon irritation which could possibly underlie the high concurrence of pelvic pain syndrome with irritable bowel syndrome.
Pain 2009 Mar
PMID:Colon mustard oil instillation induced cross-organ reflex sensitization on the pelvic-urethra reflex activity in rats. 1916 22

Spinal cord injury commonly causes chronic, neuropathic pain. The mechanisms are poorly understood but may include structural plasticity within spinal and supraspinal circuits. Our aim was to determine whether structural remodeling within the dorsal horn rostral to an incomplete injury differs from a complete spinal cord transection. Four immunohistochemical populations of primary afferent C-fibers, and descending catecholamine and serotonergic projections, were examined in segments T9-T12 at 2 and 12 weeks after a T13 clip-compression injury in adult male rats. Dorsal root ganglia were also examined. Two weeks after injury, fibers immunoreactive for calcitonin gene-related peptide (CGRP) or GDNF-family receptors (GFRalpha1, GFRalpha2, GFRalpha3) showed distinct injury responses within the superficial dorsal horn. CGRP fibers decreased, but GFRalpha1, GFRalpha2 and GFRalpha3 fibers did not change. In contrast, all groups were decreased by 12 weeks after injury. Catecholamine fibers showed a decrease at 2 weeks followed by an increase in density at 12 weeks, whereas serotonergic fibers showed a decrease (restricted to deep dorsal horn) at 12 weeks. These results show that the dorsal horn of the spinal cord undergoes substantial structural plasticity rostral to a compression injury, with the most profound effect being a prolonged and possibly permanent loss of primary afferent fibers. This loss was more extensive and more prolonged than the loss that follows spinal cord transection. Our results provide further evidence that anatomical reorganization of sensory and nociceptive dorsal horn circuits rostral to an injury could factor in the development or maintenance of spinal cord injury pain.
 ...
PMID:Spinal cord compression injury in adult rats initiates changes in dorsal horn remodeling that may correlate with development of neuropathic pain. 1923 5

In this study, we evaluated whether astrocytic and microglial activation mediates below-level neuropathic pain following spinal cord injury. Male Sprague-Dawley (225-250 g) rats were given low thoracic (T13) spinal transverse hemisection and behavioral, electrophysiological and immunohistochemical methods were used to examine the development and maintenance of below-level neuropathic pain. On postoperation day 28, both hind limbs showed significantly decreased paw withdrawal thresholds and thermal latencies as well as hyperexcitability of lumbar (L4-5) spinal wide dynamic range (WDR) neurons on both sides of spinal dorsal horn compared to sham controls (* P<0.05). Intrathecal treatment with propentofylline (PPF, 10 mM) for 7 consecutive days immediately after spinal injury attenuated the development of mechanical allodynia and thermal hyperalgesia in both hind limbs in a dose-related reduction compared to vehicle treatments (* P<0.05). Intrathecal treatment with single injections of PPF at 28 days after spinal injury, attenuated the existing mechanical allodynia and thermal hyperalgesia in both hind limbs in a dose related reduction (* P<0.05). In electrophysiological studies, topical treatment of 10 mM PPF onto the spinal surface attenuated the neuronal hyperexcitability in response to mechanical stimuli. In immunohistochemical studies, astrocytes and microglia in rats with spinal hemisection showed significantly increased GFAP and OX-42 expression in both superficial and deep dorsal horns in the lumbar spinal dorsal horn compared to sham controls (* P<0.05) that was prevented in a dose-related manner by PPF. In conclusion, our present data support astrocytic and microglial activation that contributes to below-level central neuropathic pain following spinal cord injury.
 ...
PMID:Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat. 1933 8

Priapism is a persistent penile erection lasting longer than 4 hours, without sexual stimulation. Priapism is categorized as either nonischemic (arterial, high flow) or ischemic (veno-occlusive, low flow). Ischemic priapism is considered an emergency in people. Reports of priapism in dogs are uncommon. This report describes 3 dogs with priapism; the first was considered idiopathic, the second was due to acute disc extrusion and subsequent T12-T13 hemilaminectomy, and the third was secondary to a lumbar meningomyelocoele. All 3 cases were suspected to be nonischemic priapism. The pathophysiology of the canine erection and a review of priapism in dogs and cats are discussed. Distinguishing ischemic versus nonischemic priapism and identifying and treating the underlying cause are important. Aspiration to obtain blood gas analysis may help classify the priapism and may provide pain relief. Ultrasonography aids in evaluation for vascular abnormalities and identifying etiology. If determined to be ischemic, then aspiration with the patient under sedation or anesthesia with or without irrigation should be done. Intracavernosal injections of phenylephrine and lubrication of the exposed penis are also recommended. If intracavernosal drainage and injections are not successful, or significant tissue damage has occurred, then penile amputation and perineal urethrostomy may become necessary. Systemic therapy could be considered if the priapism is not considered an emergency, and if intracavernous injections or surgical treatment are declined.
 ...
PMID:Priapism in dogs. 1950 42

In the present study we determined whether spinal cholecystokinin (CCK) or the cholecystokinin receptor is involved in below-level neuropathic pain of spinal cord injury (SCI). The effect of the CCK(B) receptor antagonist, CI-988 on mechanical allodynia and the expression level of CCK and CCK(B) receptor were investigated. Spinal hemisection was done at the T13 level in rats under enflurane anesthesia. CI-988 was administered intraperitoneally and intrathecally and behavioral tests were conducted. After systemic injection, mechanical allodynia was reduced by higher doses of CI-988 (10 and 20mg/kg). Intrathecal CI-988 (100, 200 and 500 microg) dose-dependently increased the paw withdrawal threshold in both paws. Following spinal hemisection, CCK mRNA expression increased on the ipsilateral side at the spinal segments caudal to the injury and both sides of the spinal L4-5 segments without any significant changes in CCK(B) receptor mRNA levels. These results suggest that up-regulation of spinal CCK may contribute to maintenance of mechanical allodynia following SCI and that clinical application of CI-988 or similar drugs may be useful therapeutic agents for management of central neuropathic pain.
 ...
PMID:Role of spinal cholecystokinin in neuropathic pain after spinal cord hemisection in rats. 1961 9

The most common type of chronic pain following spinal cord injury (SCI) is central neuropathic pain and SCI patients typically experience mechanical allodynia and thermal hyperalgesia. The present study was designed to examine the potential role of astrocyte gap junction connectivity in the induction and maintenance of "below-level" neuropathic pain in SCI rats. We examined the effect of intrathecal treatment with carbenoxolone (CARB), a gap junction decoupler, on SCI-induced bilateral thermal hyperalgesia and mechanical allodynia during the induction phase (postoperative days 0 to 5) and the maintenance phase (days 15 to 20) following T13 spinal cord hemisection. Immunohistochemistry was performed to determine potential SCI-induced changes in spinal astrocyte activation and phosphorylation of the NMDA receptor NR1 subunit (pNR1). CARB administered during the induction period dose-dependently attenuated the development of bilateral thermal hyperalgesia and mechanical allodynia. Intrathecal CARB also significantly reduced the bilateral SCI-induced increase in GFAP-immunoreactive (ir) staining and the number of pNR1-ir cell profiles in the spinal cord dorsal horn compared to vehicle-treated rats. In contrast, CARB treatment during the maintenance phase had no effect on the established thermal hyperalgesia and mechanical allodynia nor on spinal GFAP expression or the number of pNR1-ir cell profiles. These results indicate that gap junctions play a critical role in the activation of astrocytes distant from the site of SCI and in the subsequent phosphorylation of NMDA receptors in the lumbar spinal cord. Both of these processes appear to contribute to the induction of bilateral below-level pain in SCI rats.
 ...
PMID:Intrathecal injection of carbenoxolone, a gap junction decoupler, attenuates the induction of below-level neuropathic pain after spinal cord injury in rats. 2022 82

Central neuropathic pain occurs with multiple sclerosis, stroke, and spinal cord injury (SCI). Models of SCI are commonly used to study central neuropathic pain and are excellent at modeling gross physiological changes. Our goal was to develop a rat model of central neuropathic pain by traumatizing a discrete region of the dorsal spinal cord, thereby avoiding issues including paralysis, urinary tract infection, and autotomy. To this end, dorsal root avulsion was pursued. The model was developed by first determining the number of avulsed dorsal roots sufficient to induce below-level hindpaw mechanical allodynia. This was optimally achieved by unilateral T13 and L1 avulsion, which resulted in tissue damage confined to Lissauer's tract, dorsal horn, and dorsal columns, at the site of avulsion, with no gross physical changes at other spinal levels. Behavior following avulsion was compared to that following rhizotomy of the T13 and L1 dorsal roots, a commonly used model of neuropathic pain. Avulsion induced below-level allodynia that was more robust and enduring than that seen after rhizotomy. This, plus the lack of direct spinal cord damage associated with rhizotomy, suggests that avulsion is not synonymous with rhizotomy, and that avulsion (but not rhizotomy) is a model of central neuropathic pain. The new model described here is the first to use discrete dorsal horn damage by dorsal root avulsion to create below-level bilateral central neuropathic pain.
 ...
PMID:Below level central pain induced by discrete dorsal spinal cord injury. 2064 67


<< Previous 1 2 3 4 5 6 7 Next >>