Acupuncture points can be identified as cutaneous neurogenic inflammatory spots.

Acupuncture, a traditional medical procedure practised for over 2000 years in Asia, stimulates specific but poorly defined sites called acupoints. To date, no unique anatomical acupoint structures have been found. However, noxious sensory signals from visceral organs produce hypersensitive spots on the skin (neurogenic spots), caused by cutaneous neurogenic inflammation, in the dermatome that overlaps with visceral afferent innervations. Here, we show that an acupoint is one form of neurogenic inflammation on the skin. Various studies have demonstrated that acupoints show mechanical hypersensitivity and have high electrical conductance. Stimulation of acupoints produces needling sensations caused by the activation of small diameter afferent nerve fibres and therapeutic effects on the associated visceral organs, which is likely due to the release of endogenous opioids. The present study provides experimental evidence that neurogenic spots exhibit all the characteristics of the acupoints listed above. In addition, the stimulation of neurogenic spots by electrical, mechanical, or chemical means alleviated pathological conditions in rat colitis and hypertension models via the endogenous opioid system. Our results suggest that acupoints associated with internal organs may be identical to neurogenic inflammatory spots on the skin, which are produced by activation of somatic afferents in abnormal conditions of visceral organs.

Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats.

Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the α-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through α-adrenergic descending inhibitory systems at the spinal level.

Electroacupuncture analgesia in rat ankle sprain pain model: neural mechanisms.

OBJECTIVES: Acupuncture, an alternative medical therapy with a long history, is appealing because it can activate endogenous analgesic mechanisms by minimally invasive means. The mechanisms of acupuncture, however, are not well understood yet. The following sentence was removed from our original manuscript. One of the major problems impeding understanding of the acupuncture mechanism is lack of experimental models that mimic various forms of persistent pain that respond to acupuncture in humans. METHODS: In this review, we summarize and discuss previous and recent findings regarding electroacupuncture-induced analgesia in an ankle sprain pain model and the potential underlying mechanisms of acupuncture. RESULTS: A novel model of ankle sprain pain is introduced recently and the mechanism of electroacupuncture-induced analgesia in this model has been explored. The following sentence was removed from our original manuscript. This model provides a reproducible and quantifiable index of persistent pain at the ankle joint in rats. Acupuncture at a remote site produces long-lasting and powerful analgesia. The consistent analgesic effect of acupuncture in this model has allowed us to pursue the underlying neural mechanisms. CONCLUSIONS: These studies provide insight into the mechanisms of acupuncture analgesia in one particular form of persistent pain, and hopefully will allow us to expand our knowledge to other painful conditions.

Electroacupuncture suppresses capsaicin-induced secondary hyperalgesia through an endogenous spinal opioid mechanism.

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.

Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal alpha-adrenoceptors.

In a previous study, we showed that electroacupuncture (EA) applied to the SI-6 point on the contralateral forelimb produces long-lasting and powerful analgesia in pain caused by ankle sprain in a rat model. To investigate the underlying mechanism of EA analgesia, the present study tested the effects of various antagonists on known endogenous analgesic systems in this model. Ankle sprain was induced in anesthetized rats by overextending their right ankle with repeated forceful plantar flexion and inversion of the foot. When rats developed pain behaviors (a reduction in weight-bearing of the affected hind limb), EA was applied to the SI-6 point on the contralateral forelimb for 30 min under halothane anesthesia. EA significantly improved the weight-bearing capacity of the affected hind limb for 2h, suggesting an analgesic effect. The alpha-adrenoceptor antagonist phentolamine (2mg/kg, i.p. or 30 microg, i.t.) completely blocked the EA-induced analgesia, whereas naloxone (1mg/kg, i.p.) failed to block the effect. These results suggest that EA-induced analgesia is mediated by alpha-adrenoceptor mechanisms. Further experiments showed that intrathecal administration of yohimbine, an alpha(2)-adrenergic antagonist, reduced the EA-induced analgesia in a dose-dependent manner, whereas terazosin, an alpha(1)-adrenergic antagonist, did not produce any effect. These data suggest that the analgesic effect of EA in ankle sprain pain is, at least in part, mediated by spinal alpha(2)-adrenoceptor mechanisms.

Analgesic effect of vitamin E is mediated by reducing central sensitization in neuropathic pain.

Recent studies suggest that reactive oxygen species (ROS) are critically involved in neuropathic pain. Although vitamin E is a well-known antioxidant, its efficacy on chronic pain is not known. This study investigated the efficacy and mechanisms of vitamin E analgesia in a rat model of neuropathic pain produced by spinal nerve ligation. The effects of vitamin E were investigated using behavioral testing, electrophysiological recording of dorsal horn neurons, and determinations of phosphorylated NMDA receptor subunit 1 (pNR1) levels in the spinal dorsal horn. Results showed that a systemic single injection of a high dose or repetitive daily injections of low doses of vitamin E significantly reduced neuropathic pain behaviors. Vitamin E was also effective in producing analgesia by intrathecal injection, suggesting the importance of spinal mechanisms. In spinal dorsal horn neurons, vitamin E reduced evoked responses to mechanical stimuli as well as the sizes of their receptive fields. In addition, levels of pNR1 in neuropathic rats were also reduced by vitamin E injection. These data suggest that vitamin E produces analgesia in neuropathic rats that is, at least in part, mediated by reducing central sensitization which, in turn, is induced by peripheral nerve injury.

Acupuncture analgesia in a new rat model of ankle sprain pain.

The lack of suitable experimental animal models for persistent pain showing clear acupuncture analgesia, has been the major stumbling block in the investigation of the physiological mechanisms of acupuncture analgesia. The present study developed a new rat model of ankle sprain pain and the effect of electroacupuncture (EA) on this model was examined. A common source of persistent pain in humans is the lateral ankle sprain. To model this condition, the rat's right ankle was bent repeatedly, overextending lateral ligaments, for 4 min under halothane anesthesia. The rat subsequently showed swelling of the ankle and a reduced stepping force of the affected limb for the next several days. The reduced stepping force of the limb was presumably due to a painful ankle since systemic injection of morphine produced temporary improvement of weight bearing. EA was applied to the SI-6 acupuncture point on the contralateral forelimb for 30 min under halothane anesthesia. After the termination of EA, behavioral tests measuring stepping force were periodically conducted during the next 4h. EA produced a 40% recovery in the stepping force of the sprained foot lasting for at least 2h. The magnitude of this improvement was equivalent to that obtained after a systemic injection of 2mg/kg of morphine and this improvement of stepping pressure was interpreted as an analgesic effect. The analgesic effect was specific to the acupuncture point since (1). the analgesic effect on the ankle sprain pain model could not be mimicked by EA applied to a nearby point, LI-4 and (2). EA applied to the SI-6 point was not effective in the knee arthritis pain model. The analgesic effect could not be blocked by systemic injection of opioid antagonists naloxone or naltrexone. These data suggest that EA produces a potent analgesic effect on the ankle sprain pain model in the rat. This analgesic effect is produced by applying EA to a site remote from the painful area in a stimulus point-specific way. The present study provides a powerful experimental animal model that can be used for investigating the unique physiological mechanisms involved in acupuncture analgesia.