Phenylephrine, an α1–adrenoceptor agonist, inhibits conditioned pain modulation in healthy humans

抄録

The mechanism involved in conditioned pain modulation (CPM), a phenomenon wherein pain is controlled by heterotopic conditioning stimuli (CS), remains unclear in humans and involves a delicate balance between inhibition and excitation. The present study aimed to investigate the effect of intravenous administration of an α1–adrenoceptor agonist, phenylephrine (PE), and an α1–adrenoceptor antagonist, phentolamine (PT), on CPM in healthy humans. Two men and seven women (33.2 ± 2.7 years; mean ± standard error) participated in this double–blind randomized study. Three sequential sessions were performed in two groups: the PE and normal saline (NS, control) groups. The first (baseline ⁄ control) session involved NS infusion (PE_1st and N_1st). The second involved PE (1 mcg/kg/min, PE_2nd) or NS infusion. The third involved PT (10 mcg/kg/min, PE_3rd) or NS infusion. Painful electrical tooth stimulation was used as the test stimulus to assess somatosensory evoked potential amplitude (ampSEP) and tooth pain intensity measured with a visual analog scale (VASt). CO₂ laser stimulation was used for CS. The CPM inhibition rate was calculated as follows: [1–(ampSEP or VASt with CS) ⁄ (ampSEP or VASt without CS)] × 100 (%). One–way repeated analysis of variance and multi­ple comparisons were used for statistical analysis. In the PE_1st, PE_2nd, and PE_3rd sessions, the ampSEP inhibition rates were 42.8% ± 7.7%, 22.2% ± 9.4%, and 44.9% ± 8.9%, respectively (22.2 < 42.8; P = 0.028); the respective VASt inhibition rates were 26.0% ± 5.9%, 3.0% ± 9.0%, and 16.6% ± 3.4% (3.0 < 26.0; P = 0.046). Systemic admin­istration of PE inhibited CPM, which was restored to the baseline value by PT, suggesting the role of the noradrenergic pathways in mediating CPM.