Verbascoside administered intrathecally attenuates hyperalgesia via activating mu‐opioid receptors in a rat chronic constriction injury model

Abstract

Background: Verbascoside, a representative phenylethanoid glycoside, is widely distributed in plants and has various activities beneficial for human health.Although systemically administered verbascoside has an antinociceptive effect, little is known about the site and mechanism of its activity. The aim of the present study was to determine whether verbascoside attenuates neuropathic pain in the spinal cord and which pain regulatory systems are involved.Methods: Chronic constriction injury of the sciatic nerve was introduced to male Sprague Dawley rats. The effects of intrathecal administration of verbascoside and its components (caffeic acid and hydroxytyrosol) on mechanical hyperalgesia and cold hyperalgesia were examined using the electronic von Frey test and cold-plate test, respectively. Several antagonists of spinal pain processing receptors were administered intrathecally to evaluate their effects on the antihyperalgesic action of verbascoside. A rotarod test was performed to assess the effects on motor coordination.Results: Verbascoside attenuated mechanical and cold hyperalgesia and affected motor performance in a dose-dependent manner. Caffeic acid suppressed hyperalgesia only at high doses, whereas hydroxytyrosol did not affect hyperalgesia. The inhibitory effects of verbascoside on hyperalgesia and motor coordination were reversed by naloxone, a µ-opioid receptor antagonist.Conclusions: These findings imply that verbascoside exerts an antihyperalgesic effect by activating µ-opioid receptors in the spinal cord, and that neither caffeic acid nor hydroxytyrosol alone mediates its activity. Verbascoside shows promise for the treatment of neuropathic pain.Significance: Currently available treatments for neuropathic pain have limited efficacy in most patients. Some natural products have favourable biological activities for long-term administration such as antioxidative and neuroprotective effects. Verbascoside inhibits spinal nociceptive transmission without serious side effects to the same degree as gabapentin, a first-line remedy for neuropathic pain.Natural products may be promising candidates for novel treatments of neuropathic pain.

Minocycline Abrogates Individual Differences in Nerve Injury-Evoked Affective Disturbances in Male Rats and Prevents Associated Supraspinal Neuroinflammation

“…Motor coordination was assessed using the rat rotarod (Ugo Basile, Varese, Italy), which has been used in CCI models previously to investigate the effect of injury on motor function (Hara et al 2022 ). Rats were placed on the apparatus as it rotated at 5 rpm accelerating to 35 rpm over 3 min.…”

Minocycline abrogates individual differences in nerve injury-evoked affective disturbances in male rats and prevents associated supraspinal neuroinflammation

“…Motor coordination was assessed using the rat rotarod (Ugo Basile, Varese, Italy), which has been used in CCI models previously to investigate the effect of injury on motor function (Hara et al 2022). Rats were placed on the apparatus as it rotated at 5rpm accelerating to 35rpm over 3 minutes.…”