• YAKHAK HOEJI
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• v.43 no.3
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• pp.404-410
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• 1999

Administration of capsaicin produces acute pain and subsequent long-lasting antinociception. The antinociceptive action site of capsaicin is primarily small afferent nerve fibers. However, the effect of capsaicin on the neural activity of dorsal horn neurons are not well understood. The goal of the present experiment was to study the action of capsaicin on activity of dorsal horn neurons using c-fos immunoreactivity in the spinal cord. Intradermal injection of formalin in the hindpaw produced inflammation in the foot pad and increased the number of cells exhibiting Fos-like immunoreactivity (FLI) in the dorsal horn of the spinal cord, suggesting the hyperalgesia because of the apparent inflammation. Intradermal injection of capsaicin prior to formalin injection significantly reduced the number of cells exhibiting FLI induced by formalin and increased the paw-withdrawal latency, suggesting the hypoalgesic effect of capsaicin. Coadministeration with capsaicin of capsazepine and ruthenium red, antagonists of capsaicin receptor reversed the reduction of formalin-induced FLI by capsaicin. he antagonists also partially antagonized the antinociceptive effect of capsaicin in the paw-withdrawal test. These results further suggest that capsaicin reduces prsponses of dorsal horn neurons to the inflammatory nociceptive stimuli in the periphery. Thus, the reduction of FLI subserves the neural mechanisms underlying analgesia produced by capsaicin.

• Korean Journal of Acupuncture
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• v.19 no.1
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• pp.25-33
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• 2002

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. Injections of cocaine can produce one of the immediate-early gene, c-fos expression in the brain and behavioral activation. Acupuncture as a therapeutic intervention is widely used for the treatment of many mental disorders such as drugs of abuse. In order to investigate whether acupuncture has an influence on cocaine-induced reinforcing and behavioral effects, we examined the effect of acupuncture on cocaine-induced locomotor activity and c-Fos expression in the nucleus accumbens and the striatum using Fos-like-immunoreactivity(FLI). Male SD rats received acupuncture for 1 min after injection of cocaine hydrochloride(1 mg/kg, i.v.). The employed acupuncture point, Shenmen$(HT_7)$, has been clinically used to treat mental and psychosomatic disorders. Injections of cocaine produced a marked increase in locomotor activity and FLI in the nucleus accumbens and the striatum. Acupuncture at $HT_7$, but not at control points($PC_6,\;TE_4$ or tail), significantly attenuated cocaine-induced increase in locomotor activity and Fos-like immunoreactivity. These results demonstrated that reduction in locomotor activity by acupuncture may be reflected by reduction of postsynaptic neuronal activity in the nucleus accumbens and the striatum. Our results suggest that acupuncture may have a therapeutic effect on cocaine addiction.

• Journal of Oriental Neuropsychiatry
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• v.16 no.2
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• pp.13-24
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• 2005

Background and Objectives : Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. Yet, there are still many unanswered questions about the basic mechanism of acupuncture. Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and raised the possibility that both of these effects may be linked to the same or closely overlapping the mesolimbic dopamine systems. Neiguan (PC6) point on the pericardium channel which is associated with the brain and its mental function, has been used to treat mental, psychosomatic disorders and gastroenterological disorders. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and to measure the effect of acupuncture on Fos-like immunoreactivity. Methods : Male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Neiguan (PC6) points for 1 min after the morphine challenge. Results showed that acupuncture at the specific acupoint PC6, but not at control points (tail and HE8) significantly decreased Fos-like immunoreactivity induced by a systemic morphine challenge or a single s.c. morphine injection in the morphine-repeated animals. Results and Conclusions : These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts. Moreover, in a more general sense these results suggest that acupuncture can be used as a therapeutic intervention for correcting reversible malfunction of the body by direction of brain pathway and thus acupuncture can contribute to the biochemical balance in the central nervous system by regulating neurotransmitters.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.299-305
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• 2001

Activation of D1-like dopamine receptors by psychostimulants, such as amphetamine, upregulates the expression of immediate early gene and opioid peptide gene in the striatum. The genomic changes are regulated by phosphorylated transcription factors via complicated intracellular events. To evaluate temporal expression of the transcription factors by dopaminergic stimulation, the D1-like dopamine agonist, amphetamine or SKF82958, was systematically delivered. As intracellular markers in response to the agonist, phosphorylated cAMP response element-binding protein (pCREB), Fos-related antigens (FRA) and FosB immunoreactivity (IR) was compared at 20 and 120 min time points in the selected areas of the striatum. Semi-quantitative immunocytochemistry showed that amphetamine (5 mg/kg, i.p.) significantly increased pCREB-IR at 20 min, sustained up to 60 min and decreased at 120 min after the infusion. Like amphetamine, the full D1 agonist, SKF82958 (0.5 mg/kg, s.c.), also increased pCREB-IR at 20 min, but not at 120 min after the infusion in the dorsal striatum (caudoputaman, CPu) and shell of ventral striatum (nucleus accumbens, NAc). In contrast, FRA- and FosB-IR induced by SKF82958 was significantly increased at 120 min, but not at 20 min after the administration. These data indicate that SKF82958 mimics induction of CREB phosphorylation by amphetamine and differentially regulates temporal induction of pCREB, and FRA and FosB expression in the striatum.

• The Korean Journal of Pain
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• v.26 no.3
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• pp.255-264
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• 2013

Background: We investigated the effects of pre-emptive administration of ketamine and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after formalin injection. Methods: Eighty-four male Sprague Dawley rats were divided into 4 major groups consisting of control rats (C) (n = 12), rats given only formalin injections (F) (n = 24), and rats treated with pre-emptive administration of either ketamine (K+F) (n = 24) or norBNI (N+F) (n = 24). The non-control groups were further divided into subgroups consisting of rats that were sacrificed at 2 and 4 hours (n = 12 for each group) after formalin injection. Pain behavior was recorded for 1 hour. After 2 and 4 hours, the rats were sacrificed and the spinal cords (L4-L5 sections) were removed for immunohistochemistry and Western blot analysis. Results: The pain behavior response was reduced in the K+F group compared to the other groups during the second phase of the formalin pain response. We detected an increase in the nuclear DREAM protein level in the K+F group at 2 and 4 hours and a transient decrease in the N+F group at 2 hours; however, it increased at 4 hours after injection. Fos-like immunoreactivity (FLI) and Prodynorphin-like immunoreactivity (PLI) neurons decreased in the K+F group but increased in the N+F group at 2 hours after injection. While FLI decreased, PLI increased in all groups at 4 hours after injection. Conclusions: We suggest that NMDA and kappa opioid receptors can modulate DREAM protein expression, which can affect pain behavior and protein transcriptional processes at 2 hours and bring about either harmful or protective effects at 4 hours after formalin injection.

• Molecules and Cells
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• v.27 no.4
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• pp.417-422
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• 2009

Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.121-127
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• 2014

Acupuncture is the process of stimulating skin regions called meridians or acupoints and has been used to treat pain-related symptoms. However, the pain-relieving effects of acupuncture may be different depending on acupoints. In the present study, the effects of acupuncture on behavioral responses and c-Fos expression were evaluated using a formalin test in male Sprague-Dawley rats in order to clarify the analgesic effects of three different acupoints. Each rat received manual acupuncture at the ST36 (Zusanli), SP9 (Yinlingquan) or BL60 (Kunlun) acupoint before formalin injection. Flinching and licking behaviors were counted by two blinded investigators. Fos-like immunoreactivity was examined by immunohistochemistry in the rat spinal cord. Manual acupuncture treatment at BL60 acupoint showed significant inhibition in flinching behavior but not in licking. Manual acupuncture at ST36 or SP9 tended to inhibit flinching and licking behaviors but the effects were not statistically significant. The acupuncture at ST36, SP9, or BL60 reduced c-Fos expression as compared with the control group. These results suggest that acupuncture especially at the BL60 acupoint is more effective in relieving inflammatory pain than other acupoints.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.425-429
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• 2009

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicininduced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.

• Journal of Pharmacopuncture
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• v.7 no.1 s.12
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• pp.53-61
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• 2004

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of cocaine produce increase in locomotor activity, expression of the immediate-early gene, c-fos in the nucleus accumbens (NAc), which was one of the main dopaminergic terminal areas. Herbal-acupuncture as a therapeutic intervention has been widely used for the treatment of many functional disorders such as drug abuse. Coptidis Rhizoma (CR) and its main component, berberine (BER) were selected as herbal medicine of herbal-acupuncture. Both medicines have been known to have the therapeutic effect on the central nervous system. In order to investigate the effects of CR and BER herbalacupuncture at shenmen (HT7) point (CR/H and BER/H) on the cocaine-induced behavioral sensitization, the influence of CR/H and BER/H on repeated cocaine-induced locomotor activity, the change of c-Fos expression in the brain by immunohistochemistry were examined. Male SD rats were given CR/H (0.4mg/kg) and BER/H (0.1mg/kg) 30 min before daily injections of cocaine hydrochloride (15mg/kg. i.p.) 10 days. After 3 days withdrawal, rats received a challenge injection of cocaine (15mg/kg, i.p.). Systemic challenge with cocaine produced much larger increased locomotor activity, accumbal Fos-like immunoreactivity in the NAc. Pretreatment with CR/H and BER/H significantly inhibited cocaine-induced locomotor activity, the change of c-Fos expression in the rats. Our data demonstrated that the inhibitory effects of cocaine-induced behavioral sensitization by CR/H and BER/H were closely associated with the reduction of presynaptic dopamine release in the NAc. These results suggest that CR/H and BER/H can be effectively applied to cocaine addiction.