Role ofNMDAreceptors in the trigeminal pathway, and the modulatory effect of magnesium in a model of rat temporomandibular joint arthritis

Abstract

Temporomandibular joint (TMJ) arthritis is a common cause of orofacial pain. In the present study, the modulatory effects of N-methyl-d-aspartate receptors (NMDA-Rs) and magnesium were investigated in TMJ arthritis hypernociception. Male Wistar rats received an intra-articular injection of carrageenan (Cg) in the TMJ, and mechanical hypernociception was measured. The NMDA-R antagonist, MK-801, and magnesium chloride (MgCl₂ ) were administered before arthritis induction. Magnesium deficiency was promoted by feeding rats a synthetic magnesium-free diet for 9 d before injection of Cg. The Cg induced mechanical hypernociception that lasted for 120 h. MK-801 inhibited this hypernociceptive state. MgCl₂ pretreatment prevented Cg-induced hypernociception and altered the nociceptive threshold in the absence of Cg. Magnesium deficiency increased hypernociception and induced spontaneous hypernociceptive behavior. TMJ arthritis increased the expression of mRNA for all NMDA-R subunits and immunostaining of phosphorylated NR1 (phospho-NR1). MgCl₂ inhibited expression of NR2B mRNA and phospho-NR1 immunostaining and increased expression of NR3 mRNA. Magnesium deficiency increased expression of both NR1 and NR3 mRNAs and phospho-NR1 immunostaining in the trigeminal subnucleus caudalis. We found that magnesium modulates nociceptive behavior and induces NMDA-R subunit rearrangement in the subnucleus caudalis. The present results may lead to a better understanding of central processing in the nociceptive trigeminal pathway and the development of new approaches to treat orofacial pain with a TMJ origin.

Nitric Oxide Synthase Modulates the Antihyperalgesic Effect of the NMDA Receptor Antagonist MK-801 on Carrageenan-Induced Inflammatory Pain in Rats

“…Using the same model of pain several authors have demonstrated that MK-801 in a dose-dependent manner blocks the development of thermal hyperalgesia after systemic (Ren et al 1992a;Chen et al 2010) or local (Jackson et al 1995) administrations, as well as mechanical hyperalgesia in arthritis pain (Cavalcante et al 2013). In our study, we achieved an analgesic effect with smaller doses of MK-801 (0.5-20 μg/kg, s.c.).…”

Effects of magnesium with or without boron on headshaking behavior in horses with trigeminal‐mediated headshaking

“…This could be because of boron's ability to increase magnesium concentrations in the blood . Magnesium can then provide its physiological channel blocking effects on N‐methyl‐ d ‐aspartate (NMDA) receptors and reduce ion currents . The NMDA receptors affect trigeminal neurons at the trigeminal subnucleus caudalis (the orofacial nocioceptive processing center) in rats .…”

“…22 Magnesium can then provide its physiological channel blocking effects on N-methyl-D-aspartate (NMDA) receptors and reduce ion currents. [29][30][31][32] The NMDA receptors affect trigeminal neurons at the trigeminal subnucleus caudalis (the orofacial nocioceptive processing center) in rats. 33 Boron can also affect neurotransmitters because of its ability to form complexes with sugars.…”

Characterization of the nociceptive effect of carrageenan: Masseter versus gastrocnemius

“…There have been a few studies that used the carrageenan injection model to study pain in the orofacial region; it has been injected into the temporomandibular joint as an arthritis model to study orofacial pain and acute pain . In the masseter muscle, carrageenan injection was used to study inflammatory response, and as an inflammatory pain memory model …”

“…Carrageenan has been administered subcutaneously to study cutaneous inflammation/pain that can be assessed in tissues innervated by lumbar dorsal root ganglion neurons (i.e., the paw) or by trigeminal ganglion neurons (i.e., the vibrissal pad) . Carrageenan has also been injected into joints as an arthritis pain model …”