Possible Participation of Ionotropic Glutamate Receptors and l-Arginine-Nitric Oxide-Cyclic Guanosine Monophosphate-ATP-Sensitive K+ Channel Pathway in the Antinociceptive Activity of Cardamonin in Acute Pain Animal Models

Abstract

The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9–4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.

The Antinociceptive Responses of MTDZ to Paclitaxel−Induced Peripheral Neuropathy and Acute Nociception in Mice: Behavioral, Pharmacological, and Biochemical Approaches

“…To this end, we initially assessed the modulation of the glutamatergic and nitrergic pathways, along with the evaluation of cGMP modulation. These pathways, particularly the NMDA receptor, NOx modulation (nitrergic pathway), and cGMP pathway, collectively constitute a pivotal mechanism for combating nociception (NMDA/NO/cGMP pathway) [ 23 ].…”

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

“…Apart from the fruit and rhizomes of Alpinia species, cardamonin is also isolated from various plants of the Zingiberaceae family [ 4 ]. Cardamonin is known to possess diverse pharmacological properties against numerous pathological conditions including inflammation [ 45 ] and cancer [ 46 ]. The multitargeting properties of cardamonin is the key to its therapeutic effects against chronic diseases.…”

Regulation of pain neurotransmitters and chondrocytes metabolism mediated by voltage-gated ion channels: A narrative review

“…VGKCs play an essential role in the potential membrane regulation of primary OA chondrocytes and mediate electromechanical transduction [ 72 ]. Specifically, VGKCs subtypes (Kv7) [ 73 ], large-conductance calcium-activated K + channel (BKCa), Kir2.1, ATP-sensitive potassium channel (K-ATP), and twik-related spinal cord K + (TRESK) are closely associated with OA pain [ [74] , [75] , [76] ]. It has been reported that specific activation of the neuronal Kv7 channel in the OA rat; when the Kv7 channel is inhibited, mechanical ectopic pain and heat hyperalgesia can be alleviated, thus relieving pain caused by OA [ 77 ].…”