Alteration of metabolic connectivity in a rat model of deafferentation pain: a 18F-FDG PET/CT study

Abstract

OBJECTIVERefractory deafferentation pain has been evidenced to be related to central nervous system neuroplasticity. In this study, the authors sought to explore the underlying glucose metabolic changes in the brain after brachial plexus avulsion, particularly metabolic connectivity.METHODSRats with unilateral deafferentation following brachial plexus avulsion, a pain model of deafferentation pain, were scanned by small-animal 2-deoxy-[18F]fluoro-d-glucose (18F-FDG) PET/CT to explore the changes of metabolic connectivity among different brain regions. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of the intact forepaw were also measured for evaluating pain sensitization. Brain metabolic connectivity and TWL were compared from baseline to 1 week after brachial plexus avulsion.RESULTSAlterations of metabolic connectivity occurred not only within the unilateral hemisphere contralateral to the injured forelimb, but also in the other hemisphere and even in the connections between bilateral hemispheres. Metabolic connectivity significantly decreased between sensorimotor-related areas within the left hemisphere (contralateral to the injured forelimb) (p < 0.05), as well as between areas across bilateral hemispheres (p < 0.05). Connectivity between areas within the right hemisphere (ipsilateral to the injured forelimb) significantly increased (p = 0.034). TWL and MWT of the left (intact) forepaw after surgery were significantly lower than those at baseline (p < 0.001).CONCLUSIONSThis study revealed that unilateral brachial plexus avulsion facilitates pain sensitization in the opposite limb. A specific pattern of brain metabolic changes occurred in this procedure. Metabolic connectivity reorganized not only in the sensorimotor area corresponding to the affected forelimb, but also in extensive areas involving the bilateral hemispheres. These findings may broaden our understanding of central nervous system changes, as well as provide new information and a potential intervention target for nosogenesis of deafferentation pain.

Electroacupuncture-Related Metabolic Brain Connectivity in Neuropathic Pain due to Brachial Plexus Avulsion Injury in Rats

“…The altered metabolic connectivity revealed the changes in brain functional network, which was associated with pathophysiology of disorders. Our previous study also showed that neuropathic pain following BPAI induced metabolic connectivity changes significantly among sensorimotor-related areas and pain-related area in bilateral hemispheres (Huo et al, 2020). The specific neuroplasticity pattern might provide further insights to the mechanism of neuropathic pain following BPAI.…”

Metabolic Brain Network Analysis With 18F-FDG PET in a Rat Model of Neuropathic Pain

“…Our previous study has revealed a specific pattern of brain metabolic changes following unilateral BPAI. Metabolic connectivity based on sensorimotor-related seed ROIs indicated extensive involvement of bilateral hemispheres in the development and persistence of pain, including motor cortex, somatosensory cortex, dorsolateral thalamus, and caudate putamen (16). Meanwhile, neuropathic pain would also cause plastic changes in interconnected regions instead of segregated regions alone.…”

“…The procedure of BPAI has been described in our previous articles (14)(15)(16). Briefly, the rats were anesthetized using sodium Abbreviations: 18 pentobarbital with an intraperitoneal injection (40 mg/kg), then placed on a thermostatic operating table.…”

“…We have previously revealed changed regional brain activities following BPAI-induced neuropathic pain in rats by 18 F-FDG PET images (14)(15)(16). But growing evidence indicated that reorganization of large-scale brain connectivity and network is also a critical mechanism for chronic pain (17).…”

<p>Brain Metabolism in Rats with Neuropathic Pain Induced by Brachial Plexus Avulsion Injury and Treated via Electroacupuncture</p>

“…32 Flor et al reported that neuropathic pain due to amputation was related to expansion of the adjacent region, 12,50 which was consistent with our previous research. 19,51 Studies also revealed that cortical changes were not restricted to the sensorimotor cortex, but also an involved extensive range of areas, including the thalamus, anterior insula, and others. [52][53][54] The thalamus is the main relay of sensory and spinal nerve pathways (spinothalamic tract), which is important for the development of deafferentation pain.…”