Alleviation of mechanical stress-induced allodynia by improving blood flow in chronic constriction injury mice.

Reduced blood flow in the skin is observed in patients with neuropathic pain and in animal models. The aim of the present study was to elucidate the relationship between reduced skin blood flow and neuropathic pain in mice with a chronic constriction injury (CCI). Noradrenaline-induced contraction was enhanced in isolated plantar arteries ipsilateral to the CCI surgery compared to the contralateral arteries. Ten μM hydralazine, a peripheral vasodilator, at improved the enhanced contractile response in the ipsilateral arteries. The plantar blood flow in vivo was lower on the ipsilateral side of the CCI mice than on the contralateral side, and a 50% paw withdrawal threshold, as measured using the von Frey filament test, was lower on the former than on the latter side. An intraperitoneal injection (i.p.) of hydralazine (1 mg/kg) or phentolamine (5 mg/kg) improved blood flow in the skin and hyperalgesia in the ipsilateral plantar. In adrenalectomized CCI mice, plantar blood flow in the skin on the ipsilateral side was increased compared to in sham-operated mice, which was accompanied by alleviation of hyperalgesia. Moreover, the enhanced contractile response to noradrenaline was also observed in the ipsilateral plantar arteries isolated from the adrenalectomized CCI mice. Either hydralazine (1 mg/kg, i.p.) or an adrenalectomy barely affected mean arterial pressure in the CCI mice, whereas phentolamine (5 mg/kg, i.p.) lowered it. These results suggest that reduced blood flow in the skin contributes to neuropathic pain and that improving that blood flow with peripheral vasodilators, such as hydralazine, can alleviate it.