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

Ann Neurol. 2008 Sep;64(3):274-83. doi: 10.1002/ana.21427.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analgesics / administration & dosage*
  • Botulinum Toxins, Type A / administration & dosage*
  • Chronic Disease / drug therapy
  • Double-Blind Method
  • Female
  • Humans
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Injections, Intradermal
  • Male
  • Middle Aged
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Neuralgia / physiopathology
  • Neuromuscular Agents / administration & dosage
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / physiopathology
  • Peripheral Nervous System Diseases / drug therapy*
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / physiopathology
  • Placebos
  • Quality of Life / psychology
  • Treatment Outcome


  • Analgesics
  • Neuromuscular Agents
  • Placebos
  • Botulinum Toxins, Type A