Contributions of ADP and ATP to the increase in skeletal muscle blood flow after manual acupuncture stimulation in rats.

OBJECTIVE: To investigate the contributions of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to the increase in skeletal muscle blood flow (MBF) observed following manual acupuncture (MA) stimulation in rats. METHODS: Male Sprague-Dawley rats were used as experimental animals (300-370 g, n=40). MA was applied to the right tibialis anterior muscle (TA) for 1 min using a stainless steel acupuncture needle. In eight rats, high-performance liquid chromatography with the microdialysis technique was used to measure local extracellular concentrations of ATP, ADP, adenosine monophosphate (AMP), and adenosine in the TA. In the remaining 32 rats, fluorescent microspheres (15 µm in diameter) were used to measure MBF in the TA following pre-treatment with either the P2 receptor antagonist suramin (100 mg/kg intra-arterially) or saline (control) (n=16 each). Rats receiving MA (Suramin+MA and Saline+MA groups, n=8 each) were compared with untreated rats (Suramin and Saline groups, n=8). RESULTS: MA significantly increased the local extracellular concentration of ATP, ADP, and adenosine (p<0.05, before MA vs 30 min after MA). In addition, MA significantly increased MBF in rats pre-treated with saline or suramin (p<0.01, Saline vs Saline+MA; p<0.05, Suramin vs Suramin+MA, respectively). However, suramin significantly suppressed this MA-induced increase in MBF (p<0.05, Saline+MA vs Suramin+MA). CONCLUSIONS: These results suggest that both ATP and ADP partially contribute to the MA-induced increase in MBF via P2 receptors. However, further studies are needed to clarify the contributions of other vasodilators.

Reduced expression of Sytl 1 and Ccdc21 and impaired induction of Mt I by oxidative stress in SII-K1 knockout mice.

SII-K1 is a member of the transcription elongation factor S-II family. In the mouse, SII-K1 is expressed exclusively in the liver, kidney, heart, and skeletal muscle. Here, we report that deletion of the SII-K1 gene in mice resulted in the downregulation of the synaptotagmin-like 1 (Sytl 1) gene in liver and of the coiled-coil domain-containing 21 (Ccdc21) gene in liver and kidney. Moreover, the induction of the metallothionein I (Mt I) gene in SII-K1-deficient mice liver was impaired in diethyl maleate-induced oxidative stress conditions. Our results suggest that SII-K1 regulates these genes in vivo.

Response characteristics of nucleus submedius neurons to colo-rectal distension in the rat.

The effects of colorectal distension (CRD) were examined on neurons located in and around the nucleus submedius (Sm) in the medial thalamus of urethane-anesthetized rats. A total of 66 units (49 in the Sm and 17 in immediately surrounding regions) responding to cutaneous pinch were tested to examine their responsiveness to the CRD. All the neurons that responded to cutaneous stimulation were nociceptive specific (NS) neurons. Based on their responses to the CRD the Sm neurons were classified into three types as follows: 23 (47%) of 49 neurons in the Sm and three (18%) of 17 neurons near the Sm had tonic excitatory responses with long-lasting after-discharges (type I); nine (18%) Sm neurons and four (24%) peri-Sm neurons were tonically excited but had no after-discharge (type II); and seven (14%) Sm neurons were inhibited (type III). Ten (20%) Sm neurons and 10 (59%) peri-Sm neurons did not respond to CRD. All the excitatory and inhibitory responses to CRD increased with increasing CRD pressure. Simultaneous application of CRD and cutaneous pinch did not produce a reduced response (nocigenic inhibition). These results demonstrate that most of the Sm neurons receive convergent viscerosomatic inputs from the colon and/or rectum and from the skin, suggesting that the Sm may participate in visceral nociception.

Inhibitory effects of acupuncture manipulation and focal electrical stimulation of the nucleus submedius on a viscerosomatic reflex in anesthetized rats.

To examine the participation of nucleus submedius (Sm) in the medial thalamus of pain inhibitory systems, we investigated the effects of acupuncture and focal electrical stimulation of the Sm and adjacent brain sites (0.3 ms, 50 Hz, 50-100 microA, 10 s) on the EMG activity of the external oblique muscle evoked by colorectal distension in urethane-anesthetized Wistar rats. The viscerosomatic reflex (VSR) activity was suppressed after the administration of morphine (1.0 mg/kg, i.v.) and the effect was reversed by naloxone (0.5 mg/kg, i.v.). Transection of the spinal cord at the Th2 level also eliminated the VSR. Acupuncture manipulation applied to the cheek (manual rotation at 1 Hz) suppressed the VSR, and this inhibition was eliminated by microinjections of lidocaine into the bilateral Sm nuclei (0.5 microliter of 1.0% solution). Electrical stimulation in the ventral part but not the dorsal part of the Sm suppressed the VSR. The inhibition of the VSR induced by electrical stimulation of the Sm was not reversed by the administration of naloxone (1.0 mg/kg, i.v.). Electrical stimulation of the adjacent medial thalamic nuclei (mediodorsal nucleus (MD) or centromedial nucleus (CM)) and ventrobasal complex (VB) of the thalamus had very little effect on the VSR. These results suggests that the Sm is not only involved in the relay of nociceptive information to the cortex, but may also be involved in a non-opioid mediated pain inhibitory system and may participate, at least in part, in the suppressive effects of intense acupuncture manipulation on VSR activity.