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

Abstract

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.

Electroacupuncture Inhibits the Activity of Astrocytes in Spinal Cord in Rats with Visceral Hypersensitivity by Inhibiting P2Y1 Receptor‐Mediated MAPK/ERK Signaling Pathway

“…In this study, we found that EA at Zusanli and Shangjuxu (100 Hz for 1.05 s, 2 Hz for 2.85 s alternately, pulse width for 0.1 ms, 1 mA, 30 min/d, once a day) significantly reduced the behavioral AWR score of IBS rats suggesting that EA significantly relieved the visceral hypersensitivity in our IBS rat. It is similar to the effect of EA on visceral hypersensitivity of IBS induced by acetic acid [36], colorectal distension neonatal rat [49], formaldehyde [50], and other injuries previously reported. Previous studies have shown that chemical inflammatory injury to the colon can cause peripheral and central sensitization and increased excitability in neurons [40] and that astrocytes play an important role in the occurrence and maintenance of sensitization [41].…”

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

“…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.…”

Purinergic drug targets for gastrointestinal disorders

“…It has been suggested that P2X7R of rat dorsal root ganglia may play a role in the transmission of the nociceptive signal (Liu et al, 2015). Emerging evidence suggests that electroacupuncture may downregulate the expression of the P2X3R and ease the sensitivity to IBS visceral pain (Weng et al, 2015). It may be worth investigating AZD9056 32 in IBS and in related functional gastrointestinal disorders, since the P2X7R antagonist was shown to have some efficacy against chronic abdominal pain in CD (Eser et al, 2015).…”