stepholidine and Pain

The tetrahydroprotoberberines (THPBs) are compounds isolated from Chinese herbs that possess a unique pharmacological profile as D2 dopamine receptor antagonists and D1 receptor agonists. l-Tetrahydropalmatine (l-THP) and l-stepholidine (SPD), members of the THPB family, were shown to have potential clinical use in the treatment of pain. However, their mechanism of action is not clear. In the past decades, Chinese scientists have made a great deal of effort to explore the mechanisms by which the THPBs and its analogues elicit antinociception and their potential utility in treating drug abuse. It is now clear that the antinociception produced by l-THP is related to inhibition of D(2) dopamine receptors. The present review focuses on the recent progress made in understanding the mechanisms of l-THP- and l-SPD-mediated antinociception and the sequel of drug addiction.

Topics: Analgesics; Animals; Berberine; Berberine Alkaloids; Dopamine Antagonists; Humans; Models, Biological; Pain; Receptors, Dopamine; Substance-Related Disorders

To study the effect of tetrahydropalmatine (THP) analogs on Fos protein expression induced by formalin-pain and elucidate analgesic mechanism of THP analogs.. The pain response to Sprague Dawley rats was induced with formalin injected s.c. into the plantar surface of the right hindpaw. Fos protein expression in brain and spinal cord was investigated with immunohistochemistry. The numbers of Fos-like immunoreactive (FLI) neurons were counted with Leica Q570 image analyzer.. In the groups of THP analogs and D2 antagonist spiperone, FLI neurons induced by intraperitoneal (i.p.) injection of THP analogs and spiperone were mainly located in the striatum and accumbens nucleus, and a few FLI neurons were also in sensorimotor cortex. In the D1 antagonist, D1 agonist, D2 agonist, saline and vehicle groups, FLI neurons were seldom seen in the striatum and accumbens nucleus. Moreover, the Fos protein expression induced by l-THP and spiperone could be prevented by the pre-treatment of the D2 agonist quinpirole but not D1 agonist SKF38393. In the formalin-pain group, FLI neurons were mainly distributed in ascending pain afferent system (APAS) and descending pain modulation system (DPMS). Following i.p. THP analogs, however, the numbers of FLI neurons induced by formalin-pain in the APAS, such as dorsal horn (mainly laminae I, II, IV-VI) were markedly decreased, while the numbers of FLI neurons in the DPMS, such as periaqueductal gray (PAG) and reticular paragigantocellular lateral nucleus (RPLN) were significantly increased.. THP analogs enhanced the activity of brainstem DPMS by the blockade of D2 receptors in the striatum and accumbens nucleus, and sequentially inhibited the inputs of peripheral pain afferent message in spinal cord level.

Topics: Analgesics, Non-Narcotic; Animals; Berberine; Berberine Alkaloids; Brain; Dopamine Agonists; Dopamine Antagonists; Formaldehyde; Male; Pain; Proto-Oncogene Proteins c-fos; Quinpirole; Rats; Rats, Sprague-Dawley; Spinal Cord; Spiperone

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.

Topics: Acupuncture Analgesia; Alkaloids; Animals; Berberine; Berberine Alkaloids; Electroacupuncture; Female; Male; Pain; Rabbits; Sensory Thresholds

Topics: Analgesics; Animals; Berberine; Berberine Alkaloids; Dogs; Drug Synergism; Electroencephalography; Etorphine; Female; Heart Rate; Male; Meperidine; Mice; Pain; Rabbits; Respiration; Sensory Thresholds