Cardamonin Modulates Neuropathic Pain through the Possible Involvement of Serotonergic 5-HT1A Receptor Pathway in CCI-Induced Neuropathic Pain Mice Model

Abstract

Cardamonin, a naturally occurring chalcone isolated from Alpinia species has shown to possess strong anti-inflammatory and anti-nociceptive activities. Previous studies have demonstrated that cardamonin exerts antihyperalgesic and antiallodynic properties in chronic constriction injury (CCI)-induced neuropathic pain animal model. However, the mechanisms underlying cardamonin’s effect have yet to be fully understood. The present study aims to investigate the involvement of the serotonergic system in cardamonin induced antihyperalgesic and antiallodynic effects in CCI-induced neuropathic pain mice model. The neuropathic pain symptoms in the CCI mice model were assessed using Hargreaves Plantar test and von-Frey filament test on day 14 post-surgery. Central depletion of serotonin along the descending serotonergic pathway was done using ρ-chlorophenylalanine (PCPA, 100 mg/kg, i.p.), an inhibitor of serotonin synthesis for four consecutive days before cardamonin treatment, and was found to reverse the antihyperalgesic and antiallodynic effect produced by cardamonin. Pretreatment of the mice with several 5-HT receptor subtypes antagonists: methiothepin (5-HT1/6/77 receptor antagonist, 0.1 mg/kg), WAY 100635 (5-HT1A receptor antagonist, 1 mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5 mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3 mg/kg), and ondansetron (5-HT3 receptor antagonist, 0.5 mg/kg) were shown to abolish the effect of cardamonin induced antihyperalgesic and antiallodynic effects. Further evaluation of the 5-HT1A receptor subtype protein expressions reveals that cardamonin significantly upregulated its expression in the brainstem and spinal cord. Our results suggest that the serotonergic pathway is essential for cardamonin to exert its antineuropathic effect in CCI mice through the involvement of the 5-HT1A receptor subtype in the central nervous system.

Research progress on the mechanism of chronic neuropathic pain

“…The above antinociceptive effect exerted by the descending modulatory systems occurs at the spinal cord level mainly through descending 5-hydroxytryptamine (5-HT) and noradrenergic projection fibers ( Yamaguchi et al, 2021 , Kaswan et al, 2021 ). The central and peripheral nervous systems, especially areas such as the amygdala, the prefrontal cortex and the thalamus that are involved in pain processing, are characterized by the high expression of α and β adrenergic receptors which mediate the effects of norepinephrine.…”

Antinociceptive effects of Raphanus sativus sprouts involve the opioid and 5-HT1A serotonin receptors, cAMP/cGMP pathways, and the central activity of sulforaphane

“…The EEG segments were analyzed by fast Fourier transform using the fft.m function (0.1 Hz of spectral resolution, Hann window) (The Mathworks Inc.) in a custom-made routine. 31 The relative power spectra were recorded from the 1 to 30 Hz band and divided into the following frequency bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Then, the relative power values obtained from the segments of the same experimental condition (i.e., baseline activity or 25-30 min after treatment) were…”

“…; n = 6). 24 However, the involvement of the cAMP or cGMP pathways was analyzed by using (3) FSK (an adenylyl cyclase activator, 10 mg kg −1 ; 25 n = 7) or (4) THEO (a phosphodiesterase inhibitor, 20 mg kg −1 , i.p. ; n = 6), 26 as well as (5) l -NAME (a NO synthase inhibitor, 30 mg kg −1 , i.p.)…”

Intervertebral disc degeneration and how it leads to low back pain

“…Flavonoids have potent anti‐oxidant and anti‐inflammatory cell and tissue protective properties. 316 , 317 , 318 Alleviation of inflammation by flavonoids provides relief from nociceptive and neuropathic pain 319 through modulation of interactions with pain receptors, 320 ion channels, 321 , 322 , 323 inhibition of inflammatory cell signaling, 324 , 325 , 326 neuroglial activation, 327 and a reduction in inflammatory cytokine levels. 328 , 329 , 330 The vagus nerve and its branches have an extensive distribution in the body and its afferent and efferent fibers have motor and sensory properties that regulate many organ systems and the gut microbiome.…”