Abstract
Neuropathic pain is a major worldwide health problem. Although central sensitization has been reported in well-established neuropathic conditions, information on the acute brain activation patterns in response to peripheral nerve injury is lacking. This study first mapped the brain activity in rats immediately following spared nerve injury (SNI) of the sciatic nerve. Using blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD-fMRI), we observed sustained activation in the bilateral insular cortices (ICs), primary somatosensory cortex (S1), and cingulate cortex. Second, this study sought to link this sustained activation pattern with brain sensitization. Using manganese-enhanced magnetic resonance imaging (MEMRI), we observed enhanced activity in the ipsilateral anterior IC (AIC) in free-moving SNI rats on Days 1 and 8 post-SNI. Furthermore, enhanced functional connectivity between the ipsilateral AIC, bilateral rostral AIC, and S1 was observed on Day 8 post-SNI. Chronic electrophysiological recording experiments were conducted to confirm the tonic neuronal activation in selected brain regions. Our data provide evidence of tonic activation-dependent brain sensitization during neuropathic pain development and offer evidence that the plasticity changes in the IC and S1 may contribute to neuropathic pain development.
Highlights
Chronic pain is a major health problem affecting up to 20% of the global population
Immediate functional brain changes after spared nerve injury surgery To analyze the acute brain responses to nerve transection and determine the sustained activated brain areas possibly related to neuropathic pain development, we developed a nerve transection device for conducting SNI inside the MRI machine (Fig. 2)
Significant negative BOLD responses were found in the bilateral caudate putamen (CPu) (Fig. 4A)
Summary
Chronic pain is a major health problem affecting up to 20% of the global population. Acute pain can be properly managed, most people with chronic pain do not have access to adequate pain relief [1]. Among the most difficult cases are those with neuropathic pain initiated by primary lesions or dysfunction in the somatosensory nervous system. Many studies have investigated brain sensitization in well-established chronic neuropathic conditions. Higher tonic activity or sensitization to peripheral and central stimuli have been detected in many brain regions of humans with such conditions [2,3,4] and in animal models [5, 6]. Central sensitization at the spinal level was reported as activation-dependent and possibly
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