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In basic research, neural modulation in ulcerative colitis has been shown.1 In clinical settings, local anaesthetics such as lidocaine and ropivacaine were used, administered per rectum, for the treatment of distal ulcerative colitis with a response rate of 83% after long treatment periods (6–34 weeks) for proctosigmoiditis (n = 49).2 We report a patient with total ulcerative colitis that was ameliorated by continuous intravenous administration of lidocaine followed by oral administration of mexiletine (a congener of lidocaine).
A 24 year old man suffering from exacerbation of ulcerative colitis was admitted to our hospital. Total ulcerative colitis had been initially diagnosed one year previously. Disease extent was re-examined by barium study to reveal a total type of colitis. Conventional medical therapies, including steroids (60 mg prednisolone and steroid pulse therapy), 5-aminosalicylate, and leucocytapheresis were not effective. Abdominal pain with bleeding per rectum was very severe at night. We administered continuous systemic lidocaine (1 mg/min on the first day and 1.3 mg/min on subsequent days) only at night, resulting in complete disappearance of abdominal pain and bloody diarrhoea on the first day of treatment. This therapy was given for one week followed by oral mexiletine (300 mg/day on the first two days and 200 mg/day thereafter) administration. Prednisolone was tapered without exacerbation of colitis during this treatment, and the patient left our hospital.
Clinical reports by Kemler and colleagues,3 who reported on a patient with ulcerative colitis exacerbated by spinal cord stimulation, and by Peck and Wood,4 who obtained complete remission of a patient with ulcerative colitis after spinal cord injury, support the involvement of neural control in ulcerative colitis. Systemic lidocaine, which has been shown to suppress only spontaneous ectopic discharges without blocking nerve conduction,5 and mexiletine may modulate central and/or peripheral nerve function. Thus, in this case, the effectiveness of these drugs could be attributed to modulation of nerve function. Björck et al found that when using a 2% gel (400 mg lidocaine), maximum plasma levels were 0.5–1.9 mg/l in patients with proctitis two hours after application of the gel.2 In experimental models, plasma concentrations of 1.2–2.1 mg/l of lidocaine has been shown to be effective for neuropathic pain.6,7 Therefore, it is possible that in ulcerative colitis, lidocaine administered per rectum could exert its pharmacological effects after being absorbed into blood and has an effect on central and/or peripheral nerves. Another possibility is direct anti-inflammatory effects of these drugs on immune cells.8 However, it is not known whether systemic administration of lidocaine can achieve adequate concentrations in colonic tissue to have a direct anti-inflammatory effect on immunocytes.
A prominent feature of this case was the close association between pain and other symptoms such as bloody diarrhoea. Systemic lidocaine caused prompt symptomatic relief followed by amelioration of ulcerative colitis which was assessed by sigmoidoscopy and blood inflammatory parameters (data not shown), suggesting that pain or pain inducing substances could be a cause of exacerbation of ulcerative colitis as well as a result of the disease.
Lidocaine and mexiletine therapy could be useful for the treatment of the subgroup of patients with ulcerative colitis that are refractory to conventional medical treatments. While we do not know how to select responders to this treatment, pain could be one of the indicators.
Conflict of interest: None declared.
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