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Background: Electroacupuncture (EA), as a traditional clinical method, is widely accepted in pain clinics, but the analgesic effect of EA has not been fully demonstrated. In the present study, we investigated the effect of EA on chronic pain and expression of P2X3 receptors in the spinal cord of rats with chronic constriction injury (CCI)., Methods: The study was conducted in 2 parts. In part 1, Sprague Dawley rats were divided into 6 groups (n = 10): sham-CCI, CCI, LEA; CCI + 2 Hz EA at acupoints), HEA; CCI + 15 Hz EA at acupoints), NA-LEA (CCI + 2 Hz EA at nonacupoints), and NA-HEA (CCI + 15 Hz EA at nonacupoints). EA treatment was performed once a day on days 4 to 9 after CCI. Nociception was assessed using von Frey filaments and a hotplate apparatus. The protein and the messenger RNA (mRNA) levels of P2X3 receptors in the spinal cord were assayed by Western blotting and real-time polymerase chain reaction, respectively. In part 2, rats were divided into 5 groups (n = 10): sham-CCI, CCI, EA (CCI + EA at acupoints), NA-EA (CCI + EA at nonacupoints), and U0126 (CCI + intrathecal injection of U0126). EA treatment was conducted similar to part 1. Rats were given 5 µg U0126 in the U0126 group and 5% dimethyl sulfoxide intrathecally. Ten microliters was used as a vehicle for the other 4 groups twice a day on days 4 to 9 after CCI. Extracellular signal-regulated kinase 1/2 (ERK1/2) and ERK1/2 phosphorylation in the spinal cord were also assayed by Western blotting., Results: EA treatment exhibited significant antinociceptive effects and reduced the CCI-induced increase of both protein and mRNA expression of P2X3 receptors in the spinal cord. Furthermore, 2 Hz EA had a better analgesic effect than 15 Hz EA, and the protein and mRNA level of P2X3 receptor in spinal cord were lower in rats treated with 2 Hz EA at acupoints than 15 Hz EA at acupoints. Either EA at acupoints or intrathecal injection of U0126 relieved allodynia and hyperalgesia and reduced the expression of P2X3 receptors and ERK1/2 phosphorylation in the spinal cord., Conclusions: The data demonstrated that EA alleviates neuropathic pain behavior, at least in part, by reducing P2X3 receptor expression in spinal cord via the ERK1/2 signaling pathway. Low frequency EA has a better analgesic effect than high frequency HEA on neuropathic pain.

Objective: To evaluate the role of bladder sensory purinergic P2X3 and P2X2/3 receptors on modulating the activity of lumbosacral neurones and urinary bladder contractions in vivo in normal or spinal cord-injured (SCI) rats with neurogenic bladder overactivity., Materials and Methods: SCI was induced in female rats by complete transection at T8-T9 and experiments were performed 4 weeks later, when bladder overactivity developed. Non-transected rats were used as controls (normal rats). Neural activity was recorded in the dorsal horn of the spinal cord and field potentials were acquired in response to intravesical pressure steps via a suprapubic catheter. Field potentials were recorded under control conditions, after stimulation of bladder mucosal purinergic receptors with intravesical ATP (1 mm), and after intravenous injection of the P2X3/P2X2/3 antagonist AF-353 (10 mg/kg and 20 mg/kg). Cystometry was performed in urethane-anaesthetised rats intravesically infused with saline. AF-353 (10 mg/kg) was systemically applied after baseline recordings; the rats also received a second dose of AF-353 (20 mg/kg). Changes in the frequency of voiding (VC) and non-voiding (NVC) contractions were evaluated., Results: SCI rats had significantly higher frequencies for field potentials and NVC than NL rats. Intravesical ATP increased field potential frequency in control but not SCI rats, while systemic AF-353 significantly reduced this parameter in both groups. AF-353 also reduced the inter-contractile interval in control but not in SCI rats; however, the frequency of NVC in SCI rats was significantly reduced., Conclusion: The P2X3/P2X2/3 receptors on bladder afferent nerves positively regulate sensory activity and NVCs in overactive bladders., (© 2012 BJU INTERNATIONAL.)

Myocardial ischemia causes the production of a variety of chemical substances, which act on the cardiac afferent nerve to cause pain. Myocardial damage can affect cardiac vagal afferent activity. Survivors of myocardial infarction are often left with impaired activity of cardiac vagal sensory fibres. The nodose ganglia (NG) are lower ganglia of cardiac vagus nerve, which are chiefly visceral afferent in the sensation of heart. ATP as a possible damage signal may activate nociceptive sensory neurons. Activation of P2X(3), P2X(2/3) receptors by endogenous ATP contributes to the development of hyperalgesia. The present results have shown that the sensitivity of P2X(2/3) receptor in nodose ganglion neurons was increased after myocardial ischemic injury under electrophysiological observation. The inhibitive role of P2X(2/3) antagonist A-317491 on ATP-activated currents in myocardial ischemic rats was significantly increased, compared with that in control group at the same concentration of A-317491. The staining of P2X(2) and P2X(3) receptors in myocardial ischemic injury group appeared to be more intense than those in naive rats and myocardial ischemic rats treated with A-317491 with immunofluorescence double labeling methods. Therefore, the activity of P2X(2/3) receptors in NG neurons was involved in the transmission of myocardial ischemic nociceptive signal., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The restructuring of cardiac innervation after myocardial ischemic injury, which is often associated with an increased sympathoexcitatory reflex characterized by an increase in blood pressure and sympathetic nerve activity. This study observed whether P2X(2/3) receptor in rat superior cervical ganglion (SCG) played a role in the increased sympathoexcitatory reflex induced by myocardial ischemic nociceptive signaling. The findings showed that the systolic blood pressure, heart rate and respiration in the myocardial ischemic rats were higher than those in control rats. The content of adenosine 5'-triphosphate (ATP) from myocardial ischemic group was higher than that from control group. After myocardial ischemic rats were treated with selective P2X(2/3) receptor antagonist A-317491, the content of ATP in SCG was reduced. Coexpression value of P2X(2), P2X(3) and tyrosine hydroxylase (TH) in the SCG and myocardial tissues of myocardial ischemic group was increased significantly, compared with that in the SCG and myocardial tissues of control group. The expression value of P2X(2), P2X(3) and TH in the SCG and myocardial tissues of myocardial ischemic rats treated with A-317491 was decreased. The amplitude of the currents was much larger in myocardial ischemic group than that obtained in control group after administration of ATP with the same concentration. After the myocardial ischemic rats were treated with A-317491, ATP-activated currents were reduced. The myocardial ischemic injury induced an increase in the expression of P2X(2/3) receptor colocalization with TH and a hypersensitivity state of SCG neurons to ATP, which led to the increased sympathoexcitatory reflex., (2010 Elsevier Ltd. All rights reserved.)