Abstract: By causing long-term stimulation, gold wire implantation at acupoints has been used empirically to prolong the effects of acupuncture. This study shows that subcutaneous gold wire implantation at acupoints has long-term effects on bone regeneration in the rat ulna bone defect model.

Abstract: Reactive oxygen species (ROS) scavengers have been shown to relieve persistent pain; however, the mechanism is not clearly understood. Superoxide produced from mitochondrial oxidative phosphorylation is considered the major source of ROS in neurons during excitation where mitochondrial superoxide levels are normally controlled by superoxide dismutase (SOD-2). The present study hypothesizes that capsaicin-induced secondary hyperalgesia is a consequence of superoxide build-up in spinal dorsal horn neurons and SOD-2 is a major determinant. To test this hypothesis, the spinal levels of SOD-2 activity, inactivated SOD-2 proteins, and mitochondrial superoxide were measured and correlated to the levels of capsaicin-induced secondary hyperalgesia in mice with and without SOD-2 manipulations. The data suggest that superoxide accumulation is a culprit in the abnormal sensory processing in the spinal cord in capsaicin-induced secondary hyperalgesia. Our studies also support the notion that SOD-2 nitration is a critical mechanism that maintains elevated superoxide levels in the spinal cord after capsaicin treatment. Finally, our findings suggest a therapeutic potential for the manipulation of spinal SOD-2 activity in pain conditions.

Abstract: In behavior methods to quantify neuropathic pain, visual observations of limb-withdrawal reflexes to stimuli are not always clear-cut, so this method is partly subjective. Our current data suggest that measurement of electrophysiological EMG magnitudes enables more reliable and objective assessment for quantifying nocifensive behaviors related to neuropathic pain.

Abstract: Central sensitization, caused either by tissue inflammation or peripheral nerve injury, plays an important role in persistent pain. An animal model of capsaicin-induced pain has well-defined peripheral and central sensitization components, thus is useful for studying the analgesic effect on two separate components. The focus of this study is to examine the analgesic effects of electroacupuncture (EA) on capsaicin-induced secondary hyperalgesia, which represents central sensitization. Capsaicin (0.1%, 20 microl) was injected into the plantar side of the left hind paw, and foot withdrawal thresholds in response to von Frey stimuli (mechanical sensitivity) were determined for both primary and secondary hyperalgesia in rats. EA (2 Hz, 3 mA) was applied to various pairs of acupoints, GB30-GB34, BL40-BL60, GV2-GV6, LI3-LI6 and SI3-TE8, for 30 min under isoflurane anesthesia and then the effect of EA on mechanical sensitivity of paw was determined. EA applied to the ipsilateral SI3-TE8, but to none of the other acupoints, significantly reduced capsaicin-induced secondary hyperalgesia but not primary hyperalgesia. EA analgesic effect was inhibited by a systemic non-specific opioid receptor (OR) antagonist or an intrathecal mu- or delta-OR antagonist. EA analgesic effect was not affected by an intrathecal kappa-OR antagonist or systemic adrenergic receptor antagonist. This study demonstrates that EA produces a stimulation point-specific analgesic effect on capsaicin-induced secondary hyperalgesia (central sensitization), mediated by activating endogenous spinal mu- and delta-opioid receptors.

Abstract: Ankle sprain is a frequent injury in humans that results in pain, swelling and difficulty in walking on the affected side. Currently a suitable animal model resembling human ankle sprain is lacking. Here, we describe an animal ankle sprain model induced by ankle ligament injury (ALI) in rats. Cutting combinations of the lateral ankle ligament complex produced pain, edema and difficulty of weight bearing, thereby mimicking severe (grade III) ankle sprain in humans. Analgesic compounds, morphine and indomethacin, significantly reversed the reduced weight bearing, thus indicating that reduction of weight bearing is partially due to pain. The ALI model is a new ankle sprain model that may be useful for the study of ankle sprain pain mechanisms and treatments, as well as for the screening of new analgesic drugs.

Abstract: Scavengers of reactive oxygen species (ROS) have been shown to produce a strong antinociceptive effect on persistent pain, and mitochondria are suggested to be the main source of ROS in the spinal dorsal horn. To explore whether excessive generation of mitochondrial superoxide alone can induce pain, the effect of mitochondrial electron transport complex inhibitors on the development of mechanical hyperalgesia was examined in mice. Intrathecal injection of an electron transport complex inhibitor, antimycin A or rotenone, in normal mice resulted in a slowly developing but long-lasting and dose-dependent mechanical hyperalgesia. The levels of mechanical hyperalgesia after antimycin A, a complex III inhibitor, were higher than that with rotenone, a complex I inhibitor. A large increase of mitochondrial superoxide in the spinal dorsal horn and a strong antinociceptive effect of ROS scavengers, phenyl-N-tert-butylnitrone (PBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were observed in antimycin A-treated mice. The study indicates that the enhanced production of spinal mitochondrial superoxide alone without nerve injury can produce mechanical hyperalgesia.

Abstract: Acupuncture points (APs) are well known to be small regions of local or referred pain that are more sensitive than surrounding tissue. Based on bibliographical and clinical data, specific conditions are commonly believed to change the pain sensitivity at corresponding APs. The aim of the present study was to investigate whether the pressure pain threshold (PPT) of specific APs is associated with the severity of premenstrual syndrome. The 46 participants were female students attending a middle school. Premenstrual syndrome (PMS) was measured using a structured questionnaire, the menstruation distress questionnaire (MDQ). High PMS (HP) and low PMS (LP) groups were divided based on their MDQ scores. The PPTs at sites in the leg (the APs SP6, GB39, and LR3 and a non-AP 2-cm anterior to SP6) and in the arm (the APs PC6, TE5, and LI4 and a non-AP 2-cm proximal to PC6) were measured using an algometer. The PPT of the HP group at SP6 was significantly lower than that of the LP group (13.50 +/- 0.73 vs. 16.30 +/- 0.66 kilopascals, P < 0.05), but not at other APs or at non-APs. The findings of our study support the hypothesis that the alteration of pain threshold at specific APs is associated with the severity of corresponding diseases. Further studies are needed to determine whether an observation of pain sensitivity at the APs could be used as an adjunctive tool for the diagnosis of a clinical problem.

Abstract: The present study aimed to expand our previous findings regarding the therapeutic effects and underlying mechanisms of acupuncture at GV01 in colitis. Our results showed that acupuncture at GV01 has antinociceptive effects on referred somatic pain induced by experimental colitis, and that endogenous opioid pathways may mediate these effects.

Abstract: Gamma-aminobutyric acid (GABA) is a non-protein amino acid. It is well known for its role as an inhibitory neurotransmitter of developing and operating nervous systems in brains. In this study, a novel function of GABA in the healing process of cutaneous wounds was presented regarding anti-inflammation and fibroblast cell proliferation. The cell proliferation activity of GABA was verified through an MTT assay using murine fibroblast NIH3T3 cells. It was observed that GABA significantly inhibited the mRNA expression of iNOS, IL-1beta, and TNF-alpha, in LPS-stimulated RAW 264.7 cells. To evaluate in vivo activity of GABA in wound healing, excisional open wounds were made on the dorsal sides of Sprague-Dawley rats under anesthesia, and the healing of the wounds was apparently assessed. The molecular aspects of the healing process were also investigated by hematoxylineosin staining of the healed skin, displaying the degrees of reepithelialization and linear alignment of the granulation tissue, and immunostaining and RT-PCR analyses of fibroblast growth factor and platelet-derived growth factor, implying extracellular matrix synthesis and remodeling of the skin. The GABA treatment was effective to accelerate the healing process by suppressing inflammation and stimulating reepithelialization, compared with the epidermal growth factor treatment. The healing effect of GABA was remarkable at the early stage of wound healing, which resulted in significant reduction of the whole healing period.

Abstract: Acupoints on the Large Intestine Meridian and specific acupoints related with large intestine have been empirically used to treat large intestinal disease. However, the relationship between acupoints related with large intestine and their functions has not been investigated fully. We investigated whether large intestine-related acupoints affect colonic motility in conscious dogs implanted with electrodes at the proximal colon. Manual acupuncture was applied at the following acupoints: 7 main points on the Large Intestine Meridian (LI1, LI2, LI3, LI4, LI5, LI6, and LI11), ST25, BL25 or GV1. Acupuncture at the Large Intestine Meridian acupoints, ST25 and BL25 had no significant effects on the proximal colonic motility. However, acupuncture at GV1 depressed the proximal colonic motility by decreasing the total duration and the frequency of contractile states, which may contribute to the therapeutic effects of GV1. This study also revealed that there was no clear correlation between Large Intestine Meridian and the proximal colonic motility in conscious dogs.

Abstract: GV01 is one of the most effective acupoints to treat diarrhea in humans and animals. The present study showed that skin on the GV01 acupoint reveals tenderness and neurogenic inflammation in colonic inflammatory states, but not in normal healthy states.

Abstract: Oriental medicine uses acupuncture at the GV01 acupoint with great success to treat diarrhea. It significantly reduced the colonic motility and inflammation in colitic rats. Naloxone pretreatment blocked these effects. The therapeutic effects of acupuncture at GV01 in colitis may involve endogenous opioid pathways.