Electroacupuncture and A‐317491 depress the transmission of pain on primary afferent mediated by the P2X<sub>3</sub> receptor in rats with chronic neuropathic pain states

There are divergences between neuropathic pain and visceralgia in terms of the duration, location, and character of hyperalgesia. It is generally recognized that nociceptive receptors, including P2X receptors, may play different roles in nociceptive mechanisms. The different roles of P2X1-7 receptors have not been fully understood both in neuropathic pain and visceral hyperalgesia. In order to explore the different expressions of P2X1-7 receptors in these two hyperalgesia models, the lumbosacral dorsal root ganglion (DRG) neurons from rat sciatic nerve chronic constriction injury (CCI) model and neonatal colorectal distention (NCRD) model were studied (both the primary nociceptive neuron afferents of those two models projected to the same segment of spinal cord). Both immunohistochemistry (IHC) technique and real-time fluorescence quantitative polymerase chain reaction (RT-PCR) technology were applied to analyze the protein expression levels and nucleic acid of P2X1-7 receptors. We found that except P2X2 and P2X3, the expression levels of P2X1 and P2X5 receptors increased in neuropathic pain while those expression levels of P2X4, P2X6, and P2X7 receptors increased in visceral pain. Our results also suggested that in addition to P2X2/3 heteromeric, other P2X subunits may also involved in generation heteromeric such as P2X1/5 and/or P2X2/5 in neuropathic pain and P2X4/6 and/or P2X4/7 in visceral pain.

Section: Discussionmentioning

confidence: 98%

Differential expression of ATP-gated P2X receptors in DRG between chronic neuropathic pain and visceralgia rat models

Chen

Liu

Yue

et al. 2015

“…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]. Therefore, when studying the pathogenesis of IBS, it is necessary to investigate the relationship between the P2X receptor and IBS visceral hypersensitivity at various levels of the brain-gut axis.…”

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

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.

“…However, the exact mechanism underlying analgesia of EA at low frequency in PDN remains unclear. Previous studies showed that EA had downregulatory effects on PKC and P2X3 receptor in other animal models [26][27][28]. Thus, the present study aimed to investigate the effects of 2-Hz EA on DRG PKC and P2X3 receptor and whether PKC regulates P2X3 receptor, which may be involved in EA analgesia in PDN.…”

Section: Introductionmentioning

confidence: 99%

Suppressing PKC-dependent membrane P2X3 receptor upregulation in dorsal root ganglia mediated electroacupuncture analgesia in rat painful diabetic neuropathy

Zhou

Ying

et al. 2018

Painful diabetic neuropathy (PDN) is a common and troublesome diabetes complication. Protein kinase C (PKC)-mediated dorsal root ganglia (DRG) P2X3 receptor upregulation is one important mechanism underlying PDN. Accumulating evidence demonstrated that electroacupuncture (EA) at low frequency could effectively attenuate neuropathic pain. Our previous study showed that 2-Hz EA could relieve pain well in PDN. The study aimed to investigate whether 2-Hz EA relieves pain in PDN through suppressing PKC-mediated DRG P2X3 receptor upregulation. A 7-week feeding of high-fat and high-sugar diet plus a single injection of streptozotocin (STZ) in a dose of 35 mg/kg after a 5-week feeding of the diet successfully induced type 2 PDN in rats as revealed by the elevated body weight, fasting blood glucose, fasting insulin and insulin resistance, and the reduced paw withdrawal threshold (PWT), as well as the destructive ultrastructural change of sciatic nerve. DRG plasma membrane P2X3 receptor level and DRG PKC expression were elevated. Two-hertz EA failed to improve peripheral neuropathy; however, it reduced PWT, DRG plasma membrane P2X3 receptor level, and DRG PKC expression in PDN rats. Intraperitoneal administration of P2X3 receptor agonist αβ-meATP or PKC activator phorbol 12-myristate 13-acetate (PMA) blocked 2-Hz EA analgesia. Furthermore, PMA administration increased DRG plasma membrane P2X3 receptor level in PDN rats subject to 2-Hz EA treatment. These findings together indicated that the analgesic effect of EA in PDN is mediated by suppressing PKCdependent membrane P2X3 upregulation in DRG. EA at low frequency is a valuable approach for PDN control.