Sue A Lynch | PubMed Health

PubMed1992

Transdermal clonidine versus placebo in painful diabetic neuropathy.

In a randomized, double-blind, 2-period crossover study, 24 patients with pain due to diabetic polyneuropathy received transdermal clonidine, 0.3 mg/day, and placebo patches, each for 6 weeks. Pain was assessed daily by a 13-word descriptor list. Mean daily pain scores for the 6th week, the primary outcome variable, averaged 13% lower with clonidine than with placebo (95% conf. lim. for clonidine effect: 29% reduction to 3% increase in pain), which was not statistically significant (P = 0.11, 2-tailed paired t test). After this study, however, 9 patients who wished to continue clonidine had single (3 patients) or multiple (6 patients) cycles of clonidine withdrawal and rechallenge. Seven of 9 patients consistently reported return of pain with patch withdrawal followed by relief upon retreatment. One patient had an equivocal response, and the other patient had no relief upon retreatment. The 7 responders appeared similar to the other 17 patients in pain quality and neurological exam. We conclude that there may be a subset of patients with diabetic polyneuropathy who respond to transdermal clonidine. Further research is needed to identify features of neuropathic pain that predict drug response and to develop study designs that are more sensitive to a response in a subset of patients.

Administration, Cutaneous↗

PubMed1992

Painful neuropathy: altered central processing maintained dynamically by peripheral input.

We performed sensory assessments before and during diagnostic tourniquet-cuff and local anesthetic blocks in 4 patients diagnosed with reflex sympathetic dystrophy (RSD). All patients complained of mechano-allodynia; lightly touching the skin evoked an intense pain sensation. At detection levels, electrical stimuli were perceived as painful, suggesting that the mechano-allodynia was mediated by A beta low-threshold mechanoreceptor afferents. A beta-mediated allodynia was further supported by reaction time latencies to painful electrical stimuli at threshold for A-fiber activation and, in 1 patient, by differential cuff blocks which abolished A beta function and allodynia while thermal sensation (warm and cold) were preserved. Local anesthetic block of painful foci associated with previous trauma abolished mechano-allodynia, cold allodynia, and spontaneous pain in all patients and relieved the motor symptoms in 1 patient with tonic contractures of the toes. Tactile and thermal perception in the previously allodynic area was preserved. When the local anesthetic block waned, spontaneous pain, allodynia, and motor symptoms returned. We propose a model of neuropathic pain in which ongoing nociceptive afferent input from a peripheral focus dynamically maintains altered central processing that accounts for allodynia, spontaneous pain, and other sensory and motor abnormalities. Blocking the peripheral input causes the central processing to revert to normal, abolishing the symptoms for the duration of the block. The model accounts for sympathetically maintained (SMP) and sympathetically independent (SIP) pain. The peripheral input can be independent of sympathetic activity or driven completely or in part by activity in sympathetic efferents or by circulating catecholamines. The shared final common pathway may explain the common features of SMP and SIP.

Adult↗