Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity

Abstract

Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level.

Chronic dry eye induced corneal hypersensitivity, neuroinflammatory responses, and synaptic plasticity in the mouse trigeminal brainstem

“…The authors showed that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level. Our results showing higher Piccolo immunoreactivity in the TBSC regions in chronic DED animals are in accordance with those of the aforementioned study [37]. Thus, the increase of Piccolo staining strongly indicates that profound synaptic reorganization occurs with DED.…”

“…Accumulating evidence has suggested that chronic changes of activity in primary afferent neurons induce synaptic adaptations in the central nervous system and lead to functional remodeling of presynaptic sites [37]. Piccolo is one of the components of the presynaptic zone shown to be involved in synaptic plasticity [38].…”

“…Accumulating evidence suggests that chronic changes in the activity of primary afferent neurons induce synaptic adaptations in the central nervous system and lead to functional remodeling of presynaptic sites [37]. We thus more directly assessed possible presynaptic plasticity in the TBSC by evaluating the distribution of Piccolo in the region into which corneal neurons project.…”

“…Piccolo, a scaffolding protein of the active zone, where synaptic vesicle fusion takes place, is considered to be a presynaptic marker. In the context of chronic pain, elevated levels of Piccolo have been reported in motor and cingulate cortical structures in a rat model of chronic neuropathic orofacial pain [37]. The authors showed that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level.…”

The Localization Research of Brain Plasticity Changes after Brachial Plexus Pain: Sensory Regions or Cognitive Regions?

“…Previous studies have proved that plastic changes of various brain regions concerning pain processing contributed to the recovery of neuropathic pain. Those regions mainly involved the prefrontal-limbic-brainstem areas, the somatosensory cortices, the prefrontal cortex (PC) [7], the insular cortex (IC), the anterior cingulate cortex (ACC) [8], the basal ganglion regions, the hypothalamus (HT), and the ventral midbrain (VMB) [9, 10]. All of these changes were considered a maladaptive response of noxious damage by increased activation and reduced functional connectivity of subcortical pathways, which were believed to contribute to the increased pain sensitivity [11, 12].…”