Mechanisms of Peripheral and Central Pain Sensitization: Focus on Ocular Pain

Abstract

Persistent ocular pain caused by corneal inflammation and/or nerve injury is accompanied by significant alterations along the pain axis. Both primary sensory neurons in the trigeminal nerves and secondary neurons in the spinal trigeminal nucleus are subjected to profound morphological and functional changes, leading to peripheral and central pain sensitization. Several studies using animal models of inflammatory and neuropathic ocular pain have provided insight about the mechanisms involved in these maladaptive changes. Recently, the advent of new techniques such as optogenetics or genetic neuronal labelling has allowed the investigation of identified circuits involved in nociception, both at the spinal and trigeminal level. In this review, we will describe some of the mechanisms that contribute to the perception of ocular pain at the periphery and at the spinal trigeminal nucleus. Recent advances in the discovery of molecular and cellular mechanisms contributing to peripheral and central pain sensitization of the trigeminal pathways will be also presented.

Is the Sex Difference a Clue to the Pathomechanism of Dry Eye Disease? Watch out for the NGF-TrkA-Piezo2 Signaling Axis and the Piezo2 Channelopathy

“…However, our knowledge regarding their exact topology and functions such as pore formation, mechanical force detection and gating have not been entirely explored (Volkers et al 2015 ). Corneal mechanical stimuli are mainly transduced by Piezo2 channels (Coste et al 2010 ; Puja et al 2021 ). Nonetheless, the involvement of Piezo1 in tear production and tear evaporation should not be excluded, as these ion channels play a role in aqueous humor outflow dynamics (Zhu et al 2021 ).…”

“…Additional discussion of peripheral and central sensitization of corneal pain and their progressiveness is not the subject of this manuscript, only the aforementioned critical pathways. However, comprehensive reviews about sensitization are presented by Galor et al (Galor et al 2018 ) and Puja et al (Puja et al 2021 ).…”

Likely Pathogenic Variants of Cav1.3 and Nav1.1 Encoding Genes in Amyotrophic Lateral Sclerosis Could Elucidate the Dysregulated Pain Pathways

“…Furthermore, it is known that the Ca v 1.2 and Ca v 1.3 calcium channels play a role in the activation of the dorsal horn WDR neurons. Ca v 1.3 is the one instigating the wind-up in coordination with the activated NMDA receptors [ 58 ], not to mention that the role of the WDR neurons is noted in pain sensitization in the spinal dorsal horn [ 59 ].…”

Miswired Proprioception in Amyotrophic Lateral Sclerosis in Relation to Pain Sensation (and in Delayed Onset Muscle Soreness)—Is Piezo2 Channelopathy a Principal Transcription Activator in Proprioceptive Terminals Besides Being the Potential Primary Damage?

“…Ca v 1.2 and Ca v 1.3 L-type calcium channels have been shown to influence WDR activation in the spinal dorsal horn and Ca v 1.3 is the one responsible for initiating wind-up with the involvement of NMDA receptor activation [ 64 ]. Not to mention that the role of WDR neurons on the spinal dorsal horn is emphasized in the pain sensitization mechanism [ 65 ].…”