Korean J Pain.  2020 Apr;33(2):131-137. 10.3344/kjp.2020.33.2.131.

Increased calcium-mediated cerebral processes after peripheral injury: possible role of the brain in complex regional pain syndrome

• Nahm FS
• Lee JS
• Lee PB
• Choi E
• Han WK
• Nahm SS

• KMID: 2502636
• DOI: http://doi.org/10.3344/kjp.2020.33.2.131

Abstract

Background
Among various diseases that accompany pain, complex regional pain syndrome (CRPS) is one of the most frustrating for patients and physicians. Recently, many studies have shown functional and anatomical abnormalities in the brains of patients with CRPS. The calcium-related signaling pathway is important in various physiologic processes via calmodulin (CaM) and calcium-calmodulin kinase 2 (CaMK2). To investigate the cerebral mechanism of CRPS, we measured changes in CaM and CaMK2 expression in the cerebrum in CRPS animal models.
Methods
The chronic post-ischemia pain model was employed for CRPS model generation. After generation of the animal models, the animals were categorized into three groups based on changes in the withdrawal threshold for the affected limb: CRPS-positive (P), CRPS-negative (N), and control (C) groups. Western blot analysis was performed to measure CaM and CaMK2 expression in the rat cerebrum.
Results
Animals with a decreased withdrawal threshold (group P) showed a significant increment in cerebral CaM and CaMK2 expression (P = 0.013 and P = 0.021, respectively). However, groups N and C showed no difference in CaM and CaMK2 expression.
Conclusions
The calcium-mediated cerebral process occurs after peripheral injury in CRPS, and there can be a relationship between the cerebrum and the pathogenesis of CRPS.

Keyword

Blotting, Western; Brain; Calcium-Calmodulin-Dependent Protein Kinases; Calmodulin; Cerebrum; Complex Regional Pain Syndromes; Pain; Rats

Figure

• 

  Fig. 1 The WT after CRPS model generation. The WT was measured at 1 hr, 4 hr, 1 day, 2 days, 7 days, and 21 days after the CPIP procedure. Rats in group P showed a significant difference in WT in comparison to those in groups N and C (n = 7 rats per group, P < 0.01). Groups P, N, and C indicate the CRPS-positive (ΔWT ≥ 50%), CRPS-negative (ΔWT < 50%), and control groups, respectively. WT: withdrawal threshold, CRPS: complex regional pain syndrome, CPIP: chronic post-ischemia perfusion. *P < 0.05.

• 

  Fig. 2 Expression of cerebral calcium-calmodulin (CaM). A significant increase in the cerebral CaM level was found in group P in comparison to in groups N and C (n = 4 rats per group, P = 0.013). Error bars indicate standard errors. Groups P, N, and C indicate the CRPS-positive (ΔWT ≥ 50%), CRPS-negative (ΔWT < 50%), and control groups, respectively. *P < 0.05.

• 

  Fig. 3 Expression of cerebral calcium-calmodulin kinase 2 (CaMK2). A significant increase in the cerebral CaMK2 level was found in group P compared to in groups N and C (n = 4 rats per group, P = 0.021). Error bars indicate standard errors. Groups P, N, and C indicate the CRPS-positive (ΔWT ≥ 50%), CRPS-negative (ΔWT < 50%), and control groups, respectively. *P < 0.05.

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