Jae Hyo Kim

The role of reactive oxygen species in capsaicin-induced mechanical hyperalgesia and in the activities of dorsal horn neurons.

Abstract Previous findings that reactive oxygen species (ROS) are involved in neuropathic pain, mainly through spinal mechanisms, suggest that ROS may be involved in central sensitization. To investigate the possible role of ROS in central sensitization, we examined in rats the effects of ROS scavengers on capsaicin‐induced secondary hyperalgesia, which is known to be mediated by central sensitization. We used two different ROS scavengers: phenyl N‐tert‐butylnitrone (PBN) and 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine 1‐oxyl (TEMPOL). Intradermal capsaicin injection (20 μg in 20 μl olive oil) into the hind paw produced primary and secondary hyperalgesia. A systemic administration of PBN (100 mg/kg, i.p.) or TEMPOL (200 mg/kg, i.p.) alleviated capsaicin‐induced secondary, but not primary, hyperalgesia. Intrathecal injection of PBN (1 mg inof vertinary Surgery/anesthesiology, College of vetrinary Medic 50 μl saline) greatly reduced hyperalgesia, whereas intracerebroventricular or intradermal injection of PBN produced only a minor analgesic effect, suggesting that PBN takes effect mainly through the spinal cord. Electrophysiological recordings from wide dynamic range (WDR) neurons in the dorsal horn showed that intradermal capsaicin enhanced the evoked responses to peripheral stimuli; systemic PBN or TEMPOL restored the responses to normal levels. Removal of ROS thus restored the responsiveness of spinal WDR neurons to normal levels, suggesting that ROS is involved in central sensitization, at least in part by sensitizing WDR neurons.

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

Abstract 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.

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

Abstract 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.

Responses of spinal dorsal horn neurons to foot movements in rats with a sprained ankle

Acute ankle injuries are common problems and often lead to persistent pain. To investigate the underlying mechanism of ankle sprain pain, the response properties of spinal dorsal horn neurons were examined after ankle sprain. Acute ankle sprain was induced manually by overextending the ankle of a rat hindlimb in a direction of plantarflexion and inversion. The weight-bearing ratio (WBR) of the affected foot was used as an indicator of pain. Single unit activities of dorsal horn neurons in response to plantarflexion and inversion of the foot or ankle compression were recorded from the medial part of the deep dorsal horn, laminae IV-VI, in normal and ankle-sprained rats. One day after ankle sprain, rats showed significantly reduced WBRs on the affected foot, and this reduction was partially restored by systemic morphine. The majority of deep dorsal horn neurons responded to a single ankle stimulus modality. After ankle sprain, the mean evoked response rates were significantly increased, and afterdischarges were developed in recorded dorsal horn neurons. The ankle sprain-induced enhanced evoked responses were significantly reduced by morphine, which was reversed by naltrexone. The data indicate that movement-specific dorsal horn neuron responses were enhanced after ankle sprain in a morphine-dependent manner, thus suggesting that hyperactivity of dorsal horn neurons is an underlying mechanism of pain after ankle sprain.

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.

New Standards for Measurement in Meridians & Acupoints by Taking the Size of Normal Male Legs

Objective : Standard of measurement in Korean Medicine has been changed in dynasty and location. Thus, cun (寸) and chi (尺) as unit of measurement for meridians and acupoints could be recognized as the length of equally divided portions of a certain long bone or the distance between two anatomical landmarks and as an symbolical meaning to date. The goal of this study is to propose a new standard measurement in the metric system for the relative measurement of cun and chi as unit of measurement for meridians and acupoints in normal male legs. Methods : This study was conducted by gauging each parts of normal male legs in the metric system and comparing to the relative measurement of cun and chi as follows; to calculate 1 cun, the length of each parts was divided into the unit of cun referred to Measurement of the Bone in Neijing Lingshu (靈樞 骨度篇); it was compared the unit of cun referred to Measurement of the Bone in Neijing Lingshu with cun which was calculated by dividing subject`s height into 75 cun, respectively. Result : There has no significant difference in length of 1 cun among each leg`s areas based on a standard of subject`s height. The unit of cun by the metric length in the legs was similar to the unit of cun referred to Measurement of the Bone in Neijing Lingshu based on each subject`s height. Conclusion : It is suggested that an unit of cun as the measurement for meridians and acupoints in the male legs should be considered to the ranges from 2.4cm to 2.6cm.