Altered expression of P2X3 in vagal and spinal afferents following esophagitis in rats

Abstract

Purinergic P2X3 receptors are predominantly expressed in small diameter primary afferent neurons and activation of these receptors by adenosine triphosphate is reported to play an important role in nociceptive signaling. The objective of this study was to investigate the expression of P2X3 receptors in spinal and vagal sensory neurons and esophageal tissues following esophagitis in rats. Two groups of rats were used including 7 days fundus-ligated (7D-ligated) esophagitis and sham-operated controls. Esophagitis was produced by ligating the fundus and partial obstruction of pylorus that initiated reflux of gastric contents. The sham-operated rats underwent midline incision without surgical manipulation of the stomach. Expressions of P2X3 receptors in thoracic dorsal root ganglia (DRGs), nodose ganglia (NGs), and esophageal tissues were evaluated by RT–PCR, western blot and immunohistochemistry. Esophageal neurons were identified by retrograde transport of Fast Blue from the esophagus. There were no significant differences in P2X3 mRNA expressions in DRGs (T1–T3) and NGs between 7D-ligated and sham-operated rats. However, there was an upregulation of P2X3 mRNA in DRGs (T6–T12) and in the esophageal muscle. At protein level, P2X3 exhibited significant upregulation both in DRGs and in NGs of rats having chronic esophagitis. Immunohistochemical analysis exhibited a significant increase in P2X3 and TRPV1 co-expression in DRGs and NGs in 7D-ligated rats compared to sham-operated rats. The present findings suggest that chronic esophagitis results in upregulation of P2X3 and its co-localization with TRPV1 receptor in vagal and spinal afferents. Changes in P2X3 expression in vagal and spinal sensory neurons may contribute to esophageal hypersensitivity following acid reflux-induced esophagitis.

Nogo Receptor Homolog NgR2 Expressed in Sensory DRG Neurons Controls Epidermal Innervation by Interaction with Versican

“…Purinergic receptors of the P2X family (Xu et al, 2008;Banerjee et al, 2009;Hsieh et al, 2012), and acidsensing ion channels (ASICs) are expressed in sensory neurons of the DRG and were suggested to be involved in mechanical pain perception (Price et al, 2000. For nociception Asic2a and Asic3a are of particular interest as both are expressed by smalldiameter DRG neurons (García-Añoveros et al, 2001;Duggan et al, 2002).…”

The effect of spinal cord injury on vagal afferents.

“…Similar to other studies reporting P2X3 receptor expression in vagal sensory cell bodies using immunohistochemical techniques we also found that P2X3 receptors were highly prevalent and distributed throughout the NG (Banerjee et al, 2009a, Wang et al, 2014. These findings suggest that a large population of vagal afferents are sensitive to ATP and thus through purinergic signaling mechanisms, serve an important role in mechanosensory transduction.…”

“…However, SCI does lead to pathological changes and dysfunction of below-level target organs, such as the bladder (de Groat et al, 1990, Kruse and de Groat, 1993, and can thereby influence neuronal phenotype (Vizzard, 1997, Yoshimura et al, 1998, Vizzard, 1999, Yoshimura, 1999, Vizzard, 2000a, Qiao and Vizzard, 2002, Zvarova et al, 2004, Qiao and Vizzard, 2005, Zvarova et al, 2005, Zvara et al, 2006. Furthermore, various classes of primary sensory neurons, including vagal afferents, have been shown to alter their phenotype and 51 the expression of different receptors in response to nerve injury and tissue inflammation (Murphy et al, 1995, Neumann et al, 1996, Li et al, 1999, Michael and Priestley, 1999, Banerjee et al, 2009a, Banerjee et al, 2009b, Hill et al, 2010. In this study, we examined the effects of SCI on the neurochemistry of the NG.…”

“…These particular markers were selected based on their presence in the NG (Lewis et al, 1995, Michael and Priestley, 1999, Hubscher et al, 2001, Wang et al, 2014, involvement in the spinal and vagal circuitry (Bradbury et al, 1998, Cockayne et al, 2000, Vizzard, 2001, Young et al, 2008, Zhong et al, 2008, Banerjee et al, 2009a, McIlwrath et al, 2009) and the potential physiological role these markers may play in nociceptive signaling (Burnstock, 1996, Cook et al, 1997. In addition, anatomical evidence that the vagus nerve provides sensory innervation to the bladder in male rats and the presence of these cellular markers in bladder tissue (Liu et al, 2009, Birder, 2010, Arms and Vizzard, 2011, Birder, 2011, Birder et al, 2012, Birder and Andersson, 2013 …”

Enhancement of purinergic signalling by excessive endogenous ATP in resiniferatoxin (RTX) neuropathy

“…Previous studies documented upregulation of the P2X3 purinoceptor in peripheral neuropathic pain, for example in mechanical injury-induced focal neuropathy [4], in a chronic visceral pain model [5,6], and in chemotherapy-induced neuropathy [7]. The roles of P2X3 activation in neuropathic pain were confirmed by functional blockade [8][9][10] and by administering exogenous ATP, which evokes pain behaviors [11,12].…”