Pharmacological Studies on Lappaconitine: Possible Interaction with Endogenous Noradrenergic and Serotonergic Pathways to Induce Antinociception.

Abstract

Systemic and intracerebroventricular (i.c.v.) injections of lappaconitine (LA) produced a dose-dependent inhibition of the response to thermal stimulation in sham-operated mice as assayed by the tail-immersion test. After spinal transection, the antinociceptive potencies of s.c. or i.c.v.-administered LA were markedly re duced. Antinociception induced by systemically administered LA was clearly reduced by pretreatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine through the i.c.v. and intrathecal (i.t.) routes. When LA was administered by 1. c.v. -injection, the LA-induced antinociception was reduced by pretreatment with timolol, a Q-adrenergic antagonist, and ketanserin, a 5-HT2 antagonist. Administration of LA by the i.t. route resulted in a significant antinociceptive activity, which was also reduced by pretreat ment with phenoxybenzamine, an a-adrenergic antagonist, and mianserin, a 5-HT1 antagonist. The results of these studies suggest that the central noradrenergic and serotonergic systems may be involved in the antinociception of systemically adminis tered LA, and these pathways are mediated by /9-adrenoceptors and 5-HT2 receptors in the brain and a-adrenoceptors and 5-HT, receptors in the spinal cord.In a previous paper, we demonstrated that lappaconitine (LA) had naloxone-resistant analgesic effects (1). Furthermore, we re ported that a supraspinal-spinal interaction was important for the production of the anti nociceptive action of systemically administered LA (2) and that LA acted at the supraspinal level to inhibit nociceptive transmission or to block the spinal action of nociceptive neuro transmitters via the descending pathways (3).It is well-known that the descending inhibi tory systems play an important role in pain modulation and analgesia, and central norad renergic and serotonergic pathways, particular ly bulbospinal pathways, may modulate the transmission in these systems (4, 5).The purpose of the present study was to ex amine the role of central noradrenergic and serotonergic systems in the antinociceptive ac tion of LA. MATERIALS AND METHODS AnimalsMale mice of the Std:ddY strain, weighing 20 to 30 g, were used. Mice were maintained in a temperature and humidity-controlled room (22-23T, 50-60%) and allowed free access to food and water.

Antinociceptive Activity of Methanolic Extract ofClinacanthus nutansLeaves: Possible Mechanisms of Action Involved

“…The transmission of pain to the brain can be decreased or the inhibitory signals from the brain can be increased in order to achieve pain relief. In an attempt to identify the basic mechanism of antinociception of compound/extract, a range of studies have exploited the pharmacological tools such as various types of receptor antagonists [ 18 , 49 – 51 ]. In order to understand the mechanisms via which the compound/extract is working, the compound/extract was first pretreated with the respective receptor antagonist (receptor antagonist + compound/extract), and the percentage of antinociceptive effect observed using any of the nociceptive models was compared with the percentage of antinociceptive effect seen after the compound/extract was pretreated with distilled water (dH 2 O; dH 2 O + compound/extract).…”

Effect of various antagonists on theChanna striatusfillet extract antinociception in mice

“…The different doses of the antagonists used in this study were selected according to previous works (Bentley and Starr 1986;Pieretti et al 1999;Baratti et al 1993;Ono and Satoh 1992;Singh et al 2001;Clojnacka-Wojcik et al 1994;Verma and Kulkarni 1991;Santos et al 1995). The different doses of the antagonists used in this study were selected according to previous works (Bentley and Starr 1986;Pieretti et al 1999;Baratti et al 1993;Ono and Satoh 1992;Singh et al 2001;Clojnacka-Wojcik et al 1994;Verma and Kulkarni 1991;Santos et al 1995).…”

Analgesic effects of astilbin partially via calcium channels through regulation on CaMKII

“…The inhibition of NE and 5-HT reuptake is the mechanism of a number of effective analgesics, such as amitriptyline, imipramine, and clomipramine (Sindrup, Otto, Finnerup, & Jensen, 2005). Via modulation of the serotonergic system, lappaconitine shows analgesic properties (Ono & Satoh, 1992). Tramadol relieves pain by suppressing the reuptake of 5-HT and NE (Corona-Ramos et al, 2016).…”