Antinociceptive effects of incarvillateine, a monoterpene alkaloid from Incarvillea sinensis and possible involvement of the adenosine system

Abstract

Incarvillea sinensis is a Bignoniaceae plant used to treat rheumatism and relieve pain in traditional Chinese medicine. As a major component of I. sinensis, incarvillateine has shown analgesic activity in mice formalin tests. Using a series of animal models, this study further evaluated the effects of incarvillateine against acute, inflammatory, and neuropathic pain. Incarvillateine (10 or 20 mg/kg, i.p.) dose-dependently attenuated acetic acid-induced writhing, but did not affect thermal threshold in the hot plate test. In a Complete Freund’s Adjuvant model, incarvillateine inhibited both thermal hyperalgesia and paw edema, and increased interleukin-1β levels. Additionally, incarvillateine attenuated mechanical allodynia induced by spared nerve injury or paclitaxel, whereas normal mechanical sensation was not affected. Incarvillateine did not affect locomotor activity and time on the rotarod at analgesic doses, and no tolerance was observed after 7 consecutive daily doses. Moreover, incarvillateine-induced antinociception was attenuated by theophylline, 1,3-dipropyl-8-cyclopentylxanthine, and 3,7-dimethyl-1-propargylxanthine, but not naloxone, indicating that the effects of incarvillateine on chronic pain were related to the adenosine system, but not opioid system. These results indicate that incarvillateine is a novel analgesic compound that is effective against inflammatory and neuropathic pain, and that its effects are associated with activation of the adenosine system.

Adenosine Receptor Stimulation by Polydeoxyribonucleotide Improves Tissue Repair and Symptomology in Experimental Colitis

“…However, recent evidence suggests that DMPX also blocks A 2B (Wang et al, 2015). Therefore, it is possible that PDRN could effectively work through other adenosine receptors, including A 2B .…”

Sida tuberculata extract reduces the nociceptive response by chemical noxious stimuli in mice: Implications for mechanism of action, relation to chemical composition and molecular docking

“…Some studies have reported the receptors of these systems, present in peripheral and central sensory afferents fibers, have an important role in visceral pain maintenance (Wang et al, ; Yin et al, ). Our results indicated the antinociceptive action of STLE on writhing response was partially prevented by interacting through opioid receptor‐mediated and A1 adenosine receptor, suggesting a concomitant involvement of opioid and adenosine receptor systems in STLE antinociceptive effect from acetic acid test.…”

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

“…Uliginosin B is a naturally occurring acylphloroglucinol that reduces pain, and its MoA appears to involve adenosine signaling [94]. Incarvillateine is a complex monoterpene alkaloid that induces an antinociceptive effect, which is associated with AR signaling (using 26 and 29 at 0.1 and 1 mg/kg, i.p., respectively), but not opioid receptor activation [95]. Thus, various traditional medicines may in fact work through an adenosinergic MoA.…”