Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

l-Tetrahydropalmatine (l-THP), tetrahydroberberine (THB) and l-stepholidine (l-SPD) are the homologues of tetrahydroproto berberines and have a common antagonistic effect to central dopamine receptors. In the present experiment, the potassium iontophoretic dolorimetry was used to determine the pain threshold of rabbits. Unilateral "Hegu" point (the dorsum of the front paw, between 1st and 2nd metacarpals) and "Waiguan" point (the dorsum of the foreleg, between radius and ulna, 2 cm above the wrist joint) of each rabbit were electrically needled. The effects of iv l-THP 8 mg/kg, THB 16 mg/kg or l-SPD 4 mg/kg on electroacupuncture analgesia were investigated. The experimental results indicated that these 3 agents enhanced the potency of electroacupuncture analgesia and prolonged the duration as well. This investigation gives the evidence that the drug possessing antagonistic effect to central dopamine receptors could be used as a synergist of acupuncture analgesia.
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PMID:[Potentiation of electroacupuncture analgesia by l-tetrahydropalmatine and its analogues in rabbits]. 227 83

Previous studies have shown that dopamine (DA) is involved in electroacupuncture analgesia (EAA). L-tetrahydropalmatine (l-THP), a DA receptor antagonist was proved to potentiate EAA in both laboratory research and clinical practice. In the present study SK&F-38393 and quinpirole (Qui), selective agonists of D1 or D2 receptors respectively were injected into nucleus (N.) accumbens of rats to investigate the roles of D1 and D2 receptors in the potentiation of EAA induced by l-THP. The injection of D1 agonist SK&F-38393 (5 microg or 10 microg) attenuated the potentiation of EAA induced by l-THP, 10 microg SK&F-38393 attenuated EAA as well, while the injection of D2 agonist Qui (10 microg or 20 microg) had no effect on EAA and the potentiation of EAA induced by l-THP. DA release was shown to increase in EAA in previous work, however, whether the synthesis of DA was influenced is still unknown. In the present study, dot blot technique was applied to observe the effect of noxious stimulation or electroacupuncture on the level of tyrosine hydroxylase (TH) mRNA in rat brain. Noxious electric stimulation was found to elevate the TH mRNA level in substantia nigra (SN) and hypothalamus, while electro-acupuncture attenuated the effect of noxious stimulation on TH mRNA. The results indicate that D1 but not D2 receptor in N. accumbens plays an important role in EAA. EA might regulate the biosynthesis of DA by altering the TH gene transcription.
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PMID:Role of dopamine receptors and the changes of the tyrosine hydroxylase mRNA in acupuncture analgesia in rats. 1057 40

Blocking progesterone's metabolism to 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) with finasteride, a 5 alpha-reductase inhibitor, and effects on anxiolytic, exploratory, and antinociceptive behaviors of rats in behavioral estrus were examined. Rats in behavioral estrus received finasteride systemically (SC), to the hippocampus, or to control implant sites, the nucleus accumbens (NA) or ventral tegmental area (VTA), and were tested in horizontal crossing, open-field, elevated plus-maze, emergence, holeboard, social interaction, tailflick, pawlick, and defensive freezing tasks. Finasteride, SC or intrahippocampally, reduced 3 alpha,5 alpha-THP in the hippocampus relative to vehicle implants or finasteride to the NA or VTA. Systemic or intrahippocampal finasteride decreased central entries in the open field and open-arm time on the elevated plus-maze and increased freezing in response to shock relative to vehicle. Finasteride to the hippocampus decreased emergence latencies and increased social interaction, pawlick, and tailflick latencies relative to all other groups. Finasteride to the hippocampus of rats in behavioral estrous decreased anxiolysis and enhanced exploration and analgesia. In summary, these data demonstrate that decreases in anxiolytic behavior of behavioral estrous rats can be produced by reductions in 3 alpha,5 alpha-THP in the hippocampus, which suggest that elevations in 3 alpha,5 alpha-THP in the hippocampus may give rise to anxiolysis seen during behavioral estrus.
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PMID:Inhibiting progesterone metabolism in the hippocampus of rats in behavioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors. 1246 28

A crucial biochemical reaction in vertebrates is progesterone conversion into neuroactive metabolites such as dihydroprogesterone (5alpha-DHP) and tetrahydroprogesterone (3alpha,5alpha-THP), which regulate several neurobiological processes, including stress, depression, neuroprotection, and analgesia. 3alpha,5alpha-THP is a potent stimulator of type A receptors of GABA, the main inhibitory neurotransmitter. Here, we show that in the spinal sensory circuit progesterone conversion into 5alpha-DHP and 3alpha,5alpha-THP is inhibited dose-dependently by substance P (SP), a major mediator of painful signals. We developed a triple-labeling approach coupled with multichannel confocal microscope analysis, which revealed that, in the spinal cord (SC), SP-releasing afferents project on sensory neurons expressing simultaneously neurokinin 1 receptors (rNK1) and key enzymes catalyzing progesterone metabolism. Evidence for a potent inhibitory effect of SP on 5alpha-DHP and 3alpha,5alpha-THP formation in the SC was provided by combining pulse-chase experiments using [3H]progesterone as precursor, HPLC, recrystallization of [3H]metabolites to constant specific activity, and continuous flow detection of radioactive steroids. The action of SP on progesterone metabolism was mimicked by the rNK1-specific agonist [Sar-9,Met(O2)11]-SP. The selective rNK1 antagonist SR140333 totally reversed the effect of SP on progesterone conversion into 5alpha-DHP and 3alpha,5alpha-THP. These results provide direct evidence for the occurrence of anatomical and functional interactions between the SP-rNK1 system and neuroactive steroid-producing cells in the SC. The data suggest that, through the local control of 3alpha,5alpha-THP concentration in spinal sensory circuit, the SP-rNK1 system may indirectly interfere with GABA(A) receptor activity in the modulation of nociceptive transmission.
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PMID:Substance P inhibits progesterone conversion to neuroactive metabolites in spinal sensory circuit: a potential component of nociception. 1595 21

Identification of cellular targets pertinent for the development of effective therapies against pathological pain constitutes a difficult challenge. We combined several approaches to show that 3alpha-hydroxysteroid oxido-reductase (3alpha-HSOR), abundantly expressed in the spinal cord (SC), is a key target, the modulation of which markedly affects nociception. 3alpha-HSOR catalyzes the biosynthesis and oxidation of 3alpha,5alpha-reduced neurosteroids as allopregnanolone (3alpha,5alpha-THP), which stimulates GABA(A) receptors. Intrathecal injection of Provera (pharmacological inhibitor of 3alpha-HSOR activity) in naive rat SC decreased thermal and mechanical nociceptive thresholds assessed with behavioral methods. In contrast, pain thresholds were dose-dependently increased by 3alpha,5alpha-THP. In animals subjected to sciatic nerve injury-evoked neuropathic pain, molecular and biochemical experiments revealed an up-regulation of 3alpha-HSOR reductive activity in the SC. Enhancement of 3alpha,5alpha-THP concentration in the SC induced analgesia in neuropathic rats while Provera exacerbated their pathological state. Possibilities are opened for chronic pain control with drugs modulating 3alpha-HSOR activity in nerve cells.
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PMID:The biological activity of 3alpha-hydroxysteroid oxido-reductase in the spinal cord regulates thermal and mechanical pain thresholds after sciatic nerve injury. 1829 63