[Effect of wrist-ankle acupuncture on the expression of glutamate and NMDA receptor of the spinal dorsal horn in rats with neuropathic pain].

OBJECTIVE: To observe the effect of wrist-ankle acupuncture (WA) stimulation at "R4"- "R5" - "R6" on the expression of glutamate (Glu) and phosphorylated protein NMDAR1(p-NMDAR1) of the spinal dorsal horn in spared nerve injury (SNI) rats, so as to explore its mechanism underlying improvement of SNI. METHODS: A total of 36 SD rats were randomly divi-ded into sham operation, model and WA groups, with 12 rats in each group. The SNI procedure comprised an axotomy and ligation of the tibial and common peroneal nerves leaving the sural nerve intact. Rats of the WA group were treated by acupuncture at "R4"-"R5"-"R6" points from the 5th day to the 14th day after modeling. The mechanical pain thresholds were measured before and 5, 10 and 14 d after SNI, respectively. The cold allodynia was dectected by Acetone solution dropped onto the lateral plantar surface of the paw. Glu content and p-NMDAR1 expression of spinal dorsal horn were detected by 1H-MRS, ELISA and immunohistochemistry Methods. RESULTS: Compared with the sham operation group, the mechanical pain threshold of the model group was significantly decreased (P<0.01), the duration of cold stimulation foot contraction was increased (P<0.01), and the Glu content and p-NMDAR1 expression in the spinal dorsal horn were significantly increased (P<0.05, P<0.01). After WA intervention, the mechanical pain threshold was significantly increased (P<0.01), the duration of cold stimulation was significantly shortened (P<0.01), and Glu content and p-NMDAR1 protein expression of spinal dorsal horn were decreased significantly (P<0.05, P<0.01) in the WA group compared with the model group. CONCLUSION: WA can reduce pain sensitivity in rats with neuropathic pain, possibly by inhibiting the expression of Glu and p-NMDAR1 in the spinal dorsal horn.

Somatotopic Organization and Intensity Dependence in Driving Distinct NPY-Expressing Sympathetic Pathways by Electroacupuncture.

The neuroanatomical basis behind acupuncture practice is still poorly understood. Here, we used intersectional genetic strategy to ablate NPY+ noradrenergic neurons and/or adrenal chromaffin cells. Using endotoxin-induced systemic inflammation as a model, we found that electroacupuncture stimulation (ES) drives sympathetic pathways in somatotopy- and intensity-dependent manners. Low-intensity ES at hindlimb regions drives the vagal-adrenal axis, producing anti-inflammatory effects that depend on NPY+ adrenal chromaffin cells. High-intensity ES at the abdomen activates NPY+ splenic noradrenergic neurons via the spinal-sympathetic axis; these neurons engage incoherent feedforward regulatory loops via activation of distinct adrenergic receptors (ARs), and their ES-evoked activation produces either anti- or pro-inflammatory effects due to disease-state-dependent changes in AR profiles. The revelation of somatotopic organization and intensity dependency in driving distinct autonomic pathways could form a road map for optimizing stimulation parameters to improve both efficacy and safety in using acupuncture as a therapeutic modality.

The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain.

Cancer-induced bone pain (CIBP) is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE), isolated from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi (or Huang Qin), has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could alleviate the mechanical allodynia in CIBP rats. Intrathecal 100 µg BE could inhibit the production of IL-6 and TNF-α in the spinal cord of CIBP rats. Moreover, intrathecal 100 µg BE could effectively inhibit the activation of p-p38 and p-JNK MAPK signals in CIBP rats. The analgesic effect of BE may be associated with the inhibition of the expression of the inflammatory cytokines IL-6 and TNF-α and through the activation of p-p38 and p-JNK MAPK signals in the spinal cord. These findings suggest that BE is a promising novel analgesic agent for CIBP.

Effects of chronic electroacupuncture on depression- and anxiety-like behaviors in rats with chronic neuropathic pain.

Growing evidence indicates that chronic neuropathic pain is frequently accompanied by an array of psychiatric diseases, such as depression and anxiety. Electroacupuncture (EA), as one therapy of traditional Chinese medicine, has displayed potent antidepressant-like effects in numerous clinical studies. The present study was designed to examine the possible effects of EA on the depressive and anxiety disorders induced by neuropathic pain. A classic rat model of neuropathic pain was produced by chronic constriction injury (CCI) of the sciatic nerve. EA was performed on acupoints "Bai-Hui" (GV20) and unilateral "Yang-Ling-Quan" (GB34). The antidepressive and anxiolytic effects of EA treatment were analyzed using the forced swimming test (FST) and the elevated plus maze (EPM) test, respectively. CCI resulted in remarkable depression- and anxiety-like behaviors, whereas the chronic EA treatment significantly improved the behavioral deficits of CCI rats. Moreover, the phosphorylation level of the NMDA receptor type 1 (NR1) subunit was decreased in the hippocampus of CCI rats. Intriguingly, continuous EA treatment effectively blocked this decrease in the levels of pNR1. These results suggested that EA has antidepressive and anxiolytic effects on rats with neuropathic pain and that this might be associated with restoring the phosphorylation of NR1 in the hippocampus.

Involvement of spinal orexin A in the electroacupuncture analgesia in a rat model of post-laparotomy pain.

BACKGROUND: Orexin A (OXA, hypocretin/hcrt 1) is a newly discovered potential analgesic substance. However, whether OXA is involved in acupuncture analgesia remains unknown. The present study was designed to investigate the involvement of spinal OXA in electroacupuncture (EA) analgesia. METHODS: A modified rat model of post-laparotomy pain was adopted and evaluated. Von Frey filaments were used to measure mechanical allodynia of the hind paw and abdomen. EA at 2/15 Hz or 2/100 Hz was performed once on the bilateral ST36 and SP6 for 30 min perioperatively. SB-334867, a selective orexin 1 receptor (OX1R) antagonist with a higher affinity for OXA than OXB, was intrathecally injected to observe its effect on EA analgesia. RESULTS: OXA at 0.3 nmol and EA at 2/15 Hz produced respective analgesic effects on the model (P<0.05). Pre-surgical intrathecal administered of SB-334867 30 nmol antagonized OXA analgesia and attenuated the analgesic effect of EA (P<0.05). However, SB-334867 did not block fentanyl-induced analgesia (P>0.05). In addition, naloxone, a selective opioid receptor antagonist, failed to antagonize OXA-induced analgesia (P>0.05). CONCLUSIONS: The results of the present study indicate the involvement of OXA in EA analgesia via OX1R in an opioid-independent way.

[Study on needling depth and direction from different acupoints to sphenopalatine ganglion].

OBJECTIVE: To observe and survey the location of Xiaguan (ST 7), "Die'e" and Quanliao (SI 18) on the surface, and the needling depth and direction from the 3 points to sphenopalatine ganglion. METHODS: Fifteen corpses (30 sides) of adult male were fixed by 10% formalin. The lateral areas of face were dissected from the surface to the deep on the 3 acupoints: the electric drill with the kirschner wire punctured towards the sphenopalatine ganglion and extended to the contralateral areas according to different directions of puncturing sphenopalatine ganglion from the 3 acupoints. The corresponding puncturing points of the 3 acupoints were measured by the coordinate location method. RESULTS: (1) Surface location: the distance between Quanliao (SI 18) and "Die'e" was 21 mm and the distance between Xiaguan (ST 7) and "Die'e" was 17 mm; (2) Inserting depth of each point to sphenopalatine ganglion: the depths of Xiaguan (ST 7), "Die'e" and Quanliao (SI 18) were 49.9 mm, 46.9 mm and 46.6 mm, respectively; (3) The coordinate location of the corresponding puncturing points: the puncturing direction of Xiaguan (ST 7) was anterointernal upper corresponding to the area of connecting center between contralateral Taiyang (EX-HN 5) and Tongziliao (GB 1), the distance between the corresponding inserting point of Xiaguan (ST 7) and Sizhukong (TE 23) was 17.6 mm; the puncturing direction of "Die'e" point was posterointernal upper, and the horizontal distance from the corresponding puncture point to the zygomatic arch was 33 mm and the vertical distance from the corresponding puncture point to the eyes' outer canthus was 42 mm; the puncturing direction of Quanliao (SI 18) was posteriointernal upper and the distance between the corresponding inserting point and the area of contralateral parietal tuber, the distance between the corresponding inserting point of Quanliao (SI 18) and the connecting line of bilateral external acoustic pore was 28 mm, the distance between the corresponding inserting point of Quan-liao (SI 18) and the medial line of the head was 62 mm. CONCLUSION: Understanding the surface location, inserting depths and the general puncturing directions of the 3 points can provide basis for puncturing the sphenopalatine ganglion in clinical practice.