• Journal of Acupuncture Research
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• v.23 no.4
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• pp.149-162
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• 2006

Objectives : The aim of this study is to evaluate the analgesic effect of electroacupuncture on Jogsamni (ST36) in the collagen-induced arthritis rats and investigate the role played by opioid receptor subtypes $({\mu},\;{\delta},\;{\kappa})$ in the antinociceptive effect of electroacupuncture (EA) In the thermal hyper algesia test. Methods : Immunization of male Sprague-Dawley rats with bovine type H collagen emulsified in incomplete Freund's adjuvant, followed by booster injection 2 weeks later induced collagen-induced arthritis (CIA). The thermal hyperalgesia was evaluated weekly with tail flick latency (TFL). In the fourth week after first immunization, EA stimulation (2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni (5736) for 20 minutes. Analgesic effect was evaluated by using the tail flick latency (TFL) after intraperitoneal injection of normal saline, naloxone, naltrindole and nor-binaltorphimine respectively to CIA rats. Results : The results were as follows; 1. The TFL were gradually decreased in CIA as time elapsed after e immunization of arthrogenic collagen and the maximum value was reached between the third to fifth week. 2. EA stimulation on 5736 inhibited chronic inflammatory pain induced by CIA. 3. The analgesic effect of EA was inhibited by pretreatment of ${\mu}-receptor$ antagonist (naloxone),${\delta}-receptor$ antagonist (naltrindole) and ${\kappa}-receptor$ antagonist (nor-binaltorphimine) respectively. Conclusion : Electroacupuncture has an analgesic effect on the CIA rat and has an antinociception mediated by 8, 5, H receptors.

• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.153-165
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• 1994

In this study, we tested the influences of several ${\kappa}$ opioid ligands on the $[^3H]diprenorphine$ binding in rat and guinea pig cortex membrane preparations. Using paradigm to block ${\mu}\;and\;{\delta}$ opioid receptors with $DAMGO(1{\mu}M)$ and $DPDPE(1{\mu}M)$, $[^3H]diprenorphine$ labeled ${\kappa}$ sites. Competition analysis in both rat and guinea pig cortex has shown a single population of $[^3H]diprenorphine$ binding site with different Kd values, respectively. There is a significant difference in Ki values of (-) WIN44441 and (+)WIN44441 in both rat and guinea pig cortex. Bremazocine, (-)ethylketocyclazocine, (-)cyclazocine, nor-binaltorphimine effectively inhibited the $[^3H]diprenorphine$ binding with different Ki values in rat and guinea pig cortex. U-69,593, U-50,488H and dynorphine-A (1-8) did not inhibit the $[^3H]diprenorphine$ binding in rat but in guinea pig cortex. Nor-binaltorphimine was a ligand discriminate the ${\kappa}_1$, and ${\kappa}_2$ receptor most effectively. We, also, examined the influence of Na ion and $GTP{\gamma}S$, a nonhydrolyzable guanine nucleotide analog, on the inhibition of $[^3H]diprenorphine$ binding by diprenorphine, (-)ethyl-ketocyclazocine, U-69,593 and bremazocine. By the replacement of NaCl with N-methy-D-glucamine or addition of $GTP{\gamma}S$, Ki values of diprenorpnine were not changed and that of ethylketocyclazocine were changed significantly in both rat and guinea pig cortex. The Ki value of bremazocine was decreased by removal of Na ion, and increased by $GTP{\gamma}S$, however, was not changed by any one of either. These results suggest that there are 2 kinds of subtypes of ${\kappa}$ opioid receptor, ${\kappa}_1$, and ${\kappa}_2$, showing different Ki values for various ${\kappa}$ opioid ligands, also, bremazocine possess the antagonistic property at ${\kappa}_2$ site which is dominant subtype of K receptor in rat cortex.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.413-422
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• 2022

Background: The neocortex, including the medial prefrontal cortex (mPFC), contains many neurons expressing nitric oxide synthase (NOS). In addition, increasing evidence shows that the nitric oxide (NO) and opioid systems interact in the brain. However, there have been no studies on the interaction of the opioid and NO systems in the mPFC. The objective of this study was to investigate the effects of administrating L-arginine (L-Arg, a precursor of NO) and N(gamma)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NOS) into the mPFC for neuropathic pain in rats. Also, we used selective opioid receptor antagonists to clarify the possible participation of the opioid mechanism. Methods: Complete transection of the peroneal and tibial branches of the sciatic nerve was applied to induce neuropathic pain, and seven days later, the mPFC was cannulated bilaterally. The paw withdrawal threshold fifty percent (50% PWT) was recorded on the 14th day. Results: Microinjection of L-Arg (2.87, 11.5 and 45.92 nmol per 0.25 µL) increased 50% PWT. L-NAME (17.15 nmol per 0.25 µL) and naloxonazine (an antagonist of mu opioid receptors, 1.54 nmol per 0.25 µL) inhibited anti-allodynia induced by L-Arg (45.92 nmol per 0.25 µL). Naltrindole (a delta opioid receptor antagonist, 2.45 nmol per 0.25 µL) and nor-binaltorphimine (a kappa opioid receptor antagonist, 1.36 nmol per 0.25 µL) were unable to prevent L-Arg (45.92 nmol per 0.25 µL)-induced antiallodynia. Conclusions: Our results indicate that the NO system in the mPFC regulates neuropathic pain. Mu opioid receptors of this area might participate in pain relief caused by L-Arg.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.1-9
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• 1994

It has been shown that there are several subtypes of ${\kappa}$ opioid receptor. We examined ligand binding profiles and the effects of various opioid agonists on high potassium-stimulated release of $[^3H]$ histamine. We have evaluated the properties of $non-{\mu},\;non-{\delta},$ binding of $[^3H]\;DIP\;([^3H]\;diprenorphine),$ anonselective opioid antagonist, in rat cortex membranes. Binding $to\;{\mu}\;and\;{\delta}$ sites was inhibited by the use of an excess of competing selective agonists (DAMGO, DPDPE) for these sites. (-) Ethylketocyclazocine (EKC), DIP and bremazocine inhibited $[^3H]$ DIP binding. However, arylacetamides (U69593 and U50488H) gave little inhibition Replacement of sodium by NMDG and the addition of guanine nucleotide influenced the inhibitory potency of (-) EKC, an agonist for {\kappa}_1-and-{\kappa}_2-binding site, but not of bremazocine. This result suggests that bremazocine can be an antagonist at this binding site. Also, we have examined the opioid modulation of $K^+(30mM)-induced\;[^3H]\;histamine$ release in rat frontal cortex slices labeled with $1-[^3H]\;histidine$. The $[^3H]\; histamine$ release from cortex slices was inhibited by EKC in a concentration-dependent manner. However, the ${\delta}$ receptor selective agonists, DPDPE and deltorphine II, ${\mu}$ receptor agonists, DAMGO and TAPS, ${\kappa}_1-agonists$, U69593 and U50488H, and ${\varepsilon}-agonist,\;{\beta}-endorphin,$ did not. The concentration-response curve of EKC was shifted to right in the presence of naloxone, nor-binaltorphimine and bremazocine, respectively. These results suggest that ${\kappa}_2$ opioid receptor regulates histamine release in the fromtal cortex of the rat.