Resting-State Functional Connectivity Analyses: Brain Functional Reorganization in a Rat Model of Postherpetic Neuralgia

Abstract

Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome, similar to other chronic pains, the mechanisms of which are not fully understood. To further understand the neural mechanism of this chronic pain and its transition, we performed functional magnetic resonance imaging (fMRI) scans on PHN rat models. Twelve PHN rat models were established by intraperitoneal injection of resiniferatoxin, with an additional 12 rats serving as controls. Nociceptive behavioral tests were performed on these rats and fMRI scans were performed on days 7 and 14 after modeling. Functional connection (FC) analysis was used to investigate the brain FC alterations associated with chronic pain in PHN rats, with the anterior cingulate cortex (ACC) as a seed. Nociceptive behavioral tests showed that PHN rats presented symptoms similar to those of PHN patients. FC analysis showed that compared to the control group, the PHN group showed different FC patterns on days 7 and 14. As can be seen, the brain FC alterations in the rat model of PHN changed dynamically, shifting from brain regions processing sensory information to regions processing emotions and motives.

Keywords: chronic pain; magnetic resonance imaging; neuralgia; postherpetic; rats.

Figure 1

Mechanical pain threshold and thermal pain threshold changes in the PHN and CON groups. (A): Changes in the mechanical pain threshold of von Frey filaments in the PHN and CON groups. (B): Changes in the thermal pain threshold after thermal stimulation in the PHN and CON groups.

Figure 2

FC alterations in specific brain regions of PHN rats on day 7 (A–G). ROI heat maps show the brain regions with significantly increased FC. The color scale bar is shown in lower-right part, with corrected t-values ranging from 2 to 6. Cg, cingulate gyrus; MCx, motor cortex; SCx, sensory cortex; CPu, caudate putamen; IC, insular cortex; AMY, amygdala; VC, visual cortex; cerebellum.

Figure 3

FC alterations in specific brain regions of PHN rats on day 14 (A–G). ROI heat maps show the brain regions with significantly increased FC. The color scale bar is shown in lower-right part, with corrected t-values ranging from 2 to 6. PFC, prefrontal cortex; IC, insular cortex; Pir, piriform cortex; NAc, nucleus accumbens; SCx, sensory cortex; Hip, hippocampus; MO, medulla oblongata; cerebellum.