Role of Cholinergic Nervous System in Healing Neuropathic Lesions: Preliminary Studies and Prospective, Double-Blinded, Placebo-Controlled Studies

Abstract

The amplitudes of photo-electric-plethysmography (PPG) tracings were significantly increased by subcutaneous injections of methacholine (MC) and diminished by injections of atropine (AT) as compared with placebo injections of multi-electrolyte solution (MES) both in 8 normal subjects and 11 patients with diabetic peripheral neuropathy. AT-containing lotion delayed healing compared with placebo in the forearms of 6 normal subjects. MC-containing lotion sped healing compared with placebo in the forearms of 6 subjects with diabetic neuropathy. Thigh incisions in 6 neuropathic patients were shown to heal faster if soaked in MES rather than saline. Healing with the MES solution was shown to be further increased by the addition of MC to the solution and to be decreased by the addition of AT. The addition of MC produced erythema and an increase in the amplitude of PPG tracings. AT solutions produced blanching and a decrease in the PPG amplitude. It was concluded that (1) the slow healing characteristic of neuropathic ulcers is associated with a loss of cholinergic nerve function; (2) cholinergic stimulation will increase capillary blood flow and promote healing while cholinergic blockade has opposite effects; (3) secondary ischemia makes the ulcers susceptible to the deleterious effects of therapeutic agents such as saline; (4) the ischemic tissue will heal faster with a balanced MES than with saline; and (5) the benefits of MES on healing are augmented in patients with diabetic neuropathy by the addition of cholinergic agents to the solution.