Neuropathic pain attenuates ischemia reperfusion injury through β2-adrenergic pathway

The relationship between neuropathic pain and myocardial infarction (MI) was uncertain because of some medication or underlying diseases. This study investigated the impact of neuropathic pain on ischemia reperfusion injury using isolated rat hearts and cardiomyocytes.

Male Sprague-Dawley rats were assigned to the control and allodynia (AL) groups, with the latter subjected to the fifth lumbar spinal-nerve ligation. First, isolated hearts underwent 25-min ischemia and 90-min reperfusion to assess hemodynamic changes and MI area. Second, isolated cardiomyocytes underwent 10-min laser illumination to assess the opening of mitochondrial permeability transition pore (mPTP) and cellular hypercontraction. Lastly, expression of pro-survival kinases was measured in another cardiomyocytes using flow cytometry. AL-treated hearts were concomitantly examined regarding the involvement of β-adrenergic pathways by esmolol (ESM), β1-blocker (100μM, AL+ESM), and ICI118551 (ICI), β2-blocker (50nM, AL+ICI).

All hemodynamic variables did not change significantly in between-group comparisons except at 30min of reperfusion. MI area decreased remarkably in the AL and AL+ESM groups after 90-min reperfusion. The AL+ICI group significantly increased it as compared with the AL and AL+ESM groups. Similarly, the AL and AL+ESM groups significantly inhibited mPTP opening and cellular hypercontraction, whereas the AL+ICI group reversed these effects. Enhanced expression of pro-survival kinases was observed in the AL and AL+ESM groups, but the AL+ICI group abolished this enhancement.

Our findings suggested that neuropathic pain possessed cardioprotective effects through inhibiting mPTP opening. The underlying mechanisms were possibly regulated by β2-adrenergic activation and pro-survival kinase expression in cardiomyocytes.