P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity

Xu, Guiyun; Shenoy, Mohan; Winston, John H.; Mittal, Sahil; Pasricha, Pankaj J.

doi:10.1136/gut.2007.134221

Cited by 124 publications

(150 citation statements)

References 45 publications

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“…19,20 The rats were anesthetized with mild sedation (1% Brevital, 25 mg/kg intraperitoneal [i.p.]). A balloon made from a surgical glove finger was attached to tygon tubing.…”

Section: Behavioral Test For Nocifensive Responses To Colorectal Distmentioning

confidence: 99%

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Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

Song

Zhang

et al. 2015

J Neurogastroenterol Motil

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Background/AimsPatients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. MethodsDiabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of Na V 1.7 and Na V 1.8 of colon DRGs. ResultsSTZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of Na V 1.7 and Na V 1.8 expression in colon DRGs compared with age and sex-matched control rats. ConclusionsOur results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of Na V 1.7 and Na V 1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.

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“…19,20 The rats were anesthetized with mild sedation (1% Brevital, 25 mg/kg intraperitoneal [i.p.]). A balloon made from a surgical glove finger was attached to tygon tubing.…”

Section: Behavioral Test For Nocifensive Responses To Colorectal Distmentioning

confidence: 99%

“…As described previously, 20,22 DRG neurons innervating the colon were labeled by injection of fluorescent dye DiI (Invitrogen, New York, NY, USA) into the colon wall. Rats were anesthetized with chloral hydrate (0.36 g/kg i.p.…”

Section: Cell Retrograde Labelingmentioning

confidence: 99%

Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

Song

Zhang

et al. 2015

J Neurogastroenterol Motil

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“…As a neurotransmitter, ATP plays an important role in regulating the transduction of the visceral pain signal by binding to P2X receptors [15,16], and ATP participates in the regulation of intestinal movement and gastrointestinal secretion. P2X receptors are widely distributed in the body, and they play an important role in the formation, transduction, and regulation of neuropathic pain, inflammatory pain, and visceral pain [17][18][19][20]. Many studies have shown that purinergic (P2X) receptors are involved in pain signal transmission, in which the P2X 3 and P2X 2/3 receptors are the main subtypes [21,22].…”

Section: Introductionmentioning

confidence: 99%

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

Weng

Wu²,

Zhou

et al. 2015

Purinergic Signalling

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The aim of this study is to investigate the role of the purinergic receptor P2X 3 in the peripheral and central nervous systems during acupuncture treatment for the visceral pain of irritable bowel syndrome (IBS). A total of 24 8-day-old Sprague-Dawley (SD) neonatal male rats (SPF grade) were stimulated using colorectal distention (CRD) when the rats were awake. The modeling lasted for 2 weeks with one stimulation per day. After 6 weeks, the rats were randomly divided into three groups of eight each: (1) the normal group (NG, n= 8); (2) the model group (MG, n=8); and (3) the model+ electroacupuncture group (EA, n = 8) that received electroacupuncture at a needling depth of 5 mm at the Shangjuxu (ST37, bilateral) and Tianshu (ST25, bilateral) acupoints. The parameters of the Han's acupoint nerve stimulator (HANS) were as follows: sparse-dense wave with a frequency of 2/100 Hz, current of 2 mA, 20 min/stimulation, and one stimulation per day; the treatment was provided for seven consecutive days. At the sixth week after the treatment, the abdominal withdrawal reflex (AWR) score was determined; immunofluorescence and immunohistochemistry were used to measure the expression of the P2X 3 receptor in myenteric plexus neurons, prefrontal cortex, and anterior cingulate cortex; and, a real-time PCR assay was performed to measure the expression of P2X 3 messenger RNA (mRNA) in the dorsal root ganglion (DRG) and spinal cord. After stimulation with CRD, the expression levels of the P2X 3 receptor in the intercolonic myenteric plexus, DRG, spinal cord, prefrontal cortex, and anterior cingulate cortex were upregulated, and the sensitivity of the rats to IBS visceral pain was increased. Electroacupuncture (EA) could downregulate the expression of the P2X 3 receptor and ease the sensitivity to visceral pain. The P2X 3 receptor plays an important role in IBS visceral pain. The different levels of P2X 3 in the peripheral enteric nervous system and central nervous system mediate the effects of the EA treatment of the visceral hyperalgesia of IBS.

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“…Previous studies only documented upregulation of the P2X3 purinoceptor in DRG neurons in different neuropathic pain models [4,5,7], and peripheral P2X3 sensitization contributed to neuropathic pain, suggesting the pathology of P2X3 purinoceptors in peripheral tissues linked to neuropathic pain [17].…”

Section: Discussionmentioning

confidence: 98%

“…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].…”

Section: Introductionmentioning

confidence: 83%

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

Lin

Hsiao

et al. 2012

Purinergic Signalling

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ATP is a ligand of P2X family purinoceptors, and exogenous ATP administration evokes pain behaviors. To date, there is a lack of systematic studies to address relationships between endogenous ATP and neuropathic pain. In this report, we took advantage of a mouse model of resiniferatoxin (RTX)-induced neuropathic pain to address the role of endogenous ATP in neuropathic pain. After RTX administration, endogenous ATP markedly increased in dorsal root ganglia (DRGs) (p <0.01) and skin tissues (p<0.001). The excessive endogenous ATP was removed by apyrase, an ATP hydrolyzing enzyme, administration via either a lumbar puncture route (p<0.001) or an intraplantar injection (p<0.001), which led to the normalization of neuropathic pain. In addition, intraplantar treatment with apyrase caused mechanical analgesia. Linear analyses showed that the densities of P2X3(+) neurons (r=−0.72, p<0.0001) and P2X3(+) dermal nerves (r=−0.72, p< 0.0001) were inversely correlated with mechanical thresholds. Moreover, the contents of endogenous ATP in skin tissues were linearly correlated with P2X3(+) dermal nerves (r=0.80, p<0.0001) and mechanical thresholds (r=−0.80, p<0.0001). In summary, this study demonstrated that enhanced purinergic signalling due to an increase in endogenous ATP after RTX-induced nerve injury contributed to the development of neuropathic pain. The data in this report provide a new therapeutic strategy for pain control by targeting the endogenous ligand of purinergic signalling.

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P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity

Abstract: These data suggest that the large enhancement of P2XR expression and function may contribute to the maintenance of visceral hypersensitivity, thus identifying a specific neurobiological target for the treatment of chronic visceral hyperalgesia.

Cited by 124 publications

References 45 publications

Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

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

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