Nerve growth factor expression is up-regulated in the rat model of L-arginine–induced acute pancreatitis

Toma, Hiroki; Winston, John H.; Micci, Maria‐Adelaide; Shenoy, Mohan; Pasricha, Pankaj J.

doi:10.1053/gast.2000.19264

Cited by 58 publications

(38 citation statements)

References 34 publications

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“…This was due to a higher NGF production in the gut as revealed by the increased level of mRNA. This higher amount of NGF in inflamed tissue has also been described in other inflammatory models such as rheumatoid arthritis (Aloe et al, 1992), pancreatitis (Toma et al, 2000), and experimental colitis (Reinshagen et al, 2000); and has been associated with the increased nervous sensitivity during inflammation (Woolf et al, 1994).…”

Section: Discussionsupporting

confidence: 57%

Antinerve Growth Factor Treatment Prevents Intestinal Dysmotility inTrichinella spiralis-Infected Rats

Torrents

Torres²,

Mora³

et al. 2002

J Pharmacol Exp Ther

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Nerve growth factor (NGF) could be involved in the development of hyperalgesia as well as in nervous remodeling consequence of inflammation. Both dysmotility and increase of visceral sensitivity have been described in functional gastrointestinal disorders such as irritable bowel syndrome. Trichinella spiralis-infected rats show an exacerbated spontaneous motility and a significant increase of the excitatory response to cholecystokinin (CCK), both associated with a reversible inflammatory process and the hypertrophy of the muscle layers. In this study we determined the intestinal expression of NGF mRNA by polymerase chain reaction and NGF by enzyme-linked immunosorbent assay. We implanted serosal strain gauge transducers on duodenum, jejunum, and ileum of anesthetized Sprague-Dawley rats to record circular muscle contractions. The experimental protocol included the evaluation of intestinal spontaneous motor activity (SMA), the response to CCK-8, and the ascending contraction induced by electrical mucosal stimulation. This protocol was performed in healthy and infected nontreated rats, in healthy rats with an NGF antibody treatment (1.6 mg/rat i.p.), and in infected rats with the same treatment applied at 0 or 3 days postinfection. NGF and NGF mRNA levels in the bowel were increased during inflammation. Although anti-NGF treatments did not prevent or reverse inflammatory response, the treatment was effective in preventing the motor alterations induced by the T. spiralis infection, i.e., inhibited increased SMA, reversed altered response to CCK, and reversed in part exacerbated response to electrical stimulation.

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Section: Discussionsupporting

confidence: 57%

Antinerve Growth Factor Treatment Prevents Intestinal Dysmotility inTrichinella spiralis-Infected Rats

Torrents

Torres²,

Mora³

et al. 2002

J Pharmacol Exp Ther

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“…To date, several inflammatory mediators, including PGE 2 , nerve growth factor, and hydrogen sulfide (H 2 S), have been shown to sensitize Na v 1.8 sodium channels and therefore to significantly increase the excitability of the nociceptor. H 2 S could be a good candidate to regulate the function and expression of Na V channels because a large body of evidence shows that H 2 S plays an important role in producing sensitization in somatic pain models (37,42) and in acute and chronic visceral hyperalgesia (37,41) by affecting ion channels and membrane properties in afferent sensory neurons (30,35). Further experiments are warranted to explore the possible mediators underlying the sensitization of nociceptors under stressed conditions.…”

Section: Discussionmentioning

confidence: 99%

Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats

Xiao

Zhu

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats. Am J Physiol Gastrointest Liver Physiol 304: G311-G321, 2013. First published November 8, 2012; doi:10.1152/ajpgi.00338.2012.-Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain in association with altered bowel movements. The underlying mechanisms of visceral hypersensitivity remain elusive. This study was designed to examine the role for sodium channels in a rat model of chronic visceral hyperalgesia induced by neonatal maternal deprivation (NMD). Abdominal withdrawal reflex (AWR) scores were performed on adult male rats. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch-clamp configurations. The expression of NaV1.8 was analyzed by Western blot and quantitative real-time PCR. NMD significantly increased AWR scores, which lasted for ϳ6 wk in an association with hyperexcitability of colon DRG neurons. TTXresistant but not TTX-sensitive sodium current density was greatly enhanced in colon DRG neurons in NMD rats. Compared with controls, activation curves showed a leftward shift in NMD rats whereas inactivation curves did not differ significantly. NMD markedly accelerated the activation time of peak current amplitude without any changes in inactivation time. Furthermore, NMD remarkably enhanced expression of Na V1.8 at protein levels but not at mRNA levels in colon-related DRGs. The expression of NaV1.9 was not altered after NMD. These data suggest that NMD enhances TTXresistant sodium activity of colon DRG neurons, which is most likely mediated by a leftward shift of activation curve and by enhanced expression of NaV1.8 at protein levels, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS. dorsal root ganglion; neonatal maternal deprivation; irritable bowel syndrome; visceral pain; voltage-gated sodium channel IRRITABLE BOWEL SYNDROME (IBS) remains a common and challenging disorder for clinicians. It is defined by recurrent symptoms of abdominal pain or discomfort associated with alterations in bowel habits. The pathophysiology of IBS involves psychological disorder, altered intestinal motility, and visceral hypersensitivity (18, 33). However, the exact causes of IBS have not been clearly elucidated and effective therapeutics for the primary symptoms has been unavailable. Psychological factors and stresses appear to play an important role in the development of IBS (4, 39). Recent studies in rodents found that early life stress in the form of neonatal maternal deprivation (NMD) induced rats to develop stress-produced intestinal mucosal dysfunction and visceral hypersensitivity at adulthood, mimicking main pathophysiological features of IBS in human (3,12,20). Indeed, early traumatic experiences such as childhood neglect, abuse, loss of a parent, and lif...

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“…Several studies (6,24,30,54,62) have demonstrated that NGF tissue content increases during inflammation and modulates the function of primary sensory neurons, contributing to the development of hyperalgesia. Consistent with results obtained in rats, gene transfer of NGF into the bladder wall caused bladder hyperactivity in mice (23).…”

Section: Discussionmentioning

confidence: 99%

“…While initially described as an important factor in the development of nociceptive neurons, NGF continues to play an important role in maintaining and modulating the properties of sensory neurons in adult life (29). The expression of NGF increases during visceral inflammation and contributes to the development of visceral hypersensitivity (6,7,54). On the basis of these results, we examined the following four hypotheses: 1) visceral inflammation sensitizes visceral afferent pathways innervating different organs and converging onto the same spinal segments (viscerovisceral convergence); 2) visceral inflammation sensitizes somatic afferent pathways in areas of pain referral (viscerosomatic convergence); 3) somatic inflammation sensitizes visceral afferents converging onto the same spinal segments (somatovisceral convergence); and 4) transient overexpression of NGF in visceral or somatic structures sensitizes afferent pathways comparably with the effects seen with inflammation.…”

mentioning

confidence: 99%

Convergence of sensory pathways in the development of somatic and visceral hypersensitivity

Bielefeldt¹,

Lamb²,

Gebhart³

2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Sensory neurons innervating different tissues converge onto second-order neurons in the spinal cord. We examined whether inflammation or transient overexpression of nerve growth factor (NGF) in one tissue triggers hypersensitivity in referral sites. Thresholds to mechanical and thermal stimulation of the hindpaw, visceromotor responses to colorectal distension, and cystometrograms were performed in appropriate controls and mice with experimentally induced cystitis, inflammation of the hindpaw or front paw, or injection of viral vectors encoding NGF or green fluorescent protein (GFP). Cystitis and NGF but not GFP overexpression in the bladder triggered bladder hyperactivity associated with mechanical and thermal hypersensitivity in cutaneous referral sites and enhanced responses to colorectal distension. Hindpaw inflammation and injection of the NGF- but not GFP-encoding viral vector or front paw inflammation induced mechanical and thermal hyperalgesia in the affected hindpaw and increased responses to colorectal distension without altering the micturition reflex. In conclusion, sensitization of sensory pathways by inflammation or NGF contributes to the development of hypersensitivity in neighboring organs and cutaneous referral sites and provides a potential mechanism underlying the coexistence of pain syndromes in patients with functional diseases.

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Nerve growth factor expression is up-regulated in the rat model of L-arginine–induced acute pancreatitis

Cited by 58 publications

References 34 publications

Antinerve Growth Factor Treatment Prevents Intestinal Dysmotility inTrichinella spiralis-Infected Rats

Antinerve Growth Factor Treatment Prevents Intestinal Dysmotility inTrichinella spiralis-Infected Rats

Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats

Convergence of sensory pathways in the development of somatic and visceral hypersensitivity

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