Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain.

OBJECTIVE: Botulinum toxin type A (BTX-A) has been reported to have analgesic effects independent of its action on muscle tone, possibly by acting on neurogenic inflammation. Such a mechanism may be involved in peripheral neuropathic pain. METHODS: A possible direct analgesic effect of BTX-A pain processing was investigated in 29 patients with focal painful neuropathies and mechanical allodynia using a randomized, double-blind, placebo-controlled design. Patients received a one-time intradermal administration of BTX-A (20-190 units) into the painful area. Outcome measures, evaluated at baseline, then at 4, 12, and 24 weeks, included average spontaneous pain intensity, quantified testing of thermal and mechanical perception and pain, allodynia to brushing (area, intensity), neuropathic symptoms, clinical global impression, and quality of life. RESULTS: BTX-A treatment, relative to placebo, was associated with persistent effects on spontaneous pain intensity from 2 weeks after the injection to 14 weeks. These effects correlated with the preservation of thermal sensation at baseline (p < 0.05). BTX also improved allodynia to brush and decreased pain thresholds to cold, without affecting perception thresholds. There were sustained improvements in the proportion of responders (number needed to treat for 50% pain relief: 3.03 at 12 weeks), neuropathic symptoms, and general activity. Most patients reported pain during the injections, but there were no further local or systemic side effects. INTERPRETATION: These results indicate for the first time that BTX-A may induce direct analgesic effects in patients with chronic neuropathic pain independent of its effects on muscle tone and suggest novel indications for BTX-A in analgesia.

Investigation of the paradoxical painful sensation ('illusion of pain') produced by a thermal grill.

A paradoxical painful sensation can be elicited by the simultaneous application of innocuous warm and cold stimuli to the skin. In the present study, we analyzed the conditions of production of this unique experimental illusion of pain in 52 healthy volunteers (27 men, 25 women). The stimuli were produced by a thermode composed of six bars whose temperature was controlled by Peltier elements. The temperature of alternate (even- and odd-numbered) bars could be controlled independently to produce various patterns of the 'thermal grill'. After measuring the cold and heat pain thresholds, a series of combinations of warm and cold stimuli, whose distance to the thermal pain threshold was at least 4 degrees C, were applied on the palmar surface of the right hand during 30s. After each stimulus, the subjects had to describe and rate their sensations on visual analog scales. Paradoxical painful sensations, mostly described as burning, were reported by all the subjects but three. However, the phenomenon was less frequent in approximately one third of ('low responder') volunteers. The frequency and intensity of such painful sensations were directly related to the magnitude (i.e. 5-25 degrees C) of the difference of the temperature between the warm and cold bars of the grill. The combination of increasingly colder temperature to a given warm temperature induces similar effects as combining increasingly warmer temperature to a given cold temperature. These results suggest that pain can be the result of a simple addition of non-noxious warm and cold signals.