Hyperbaric oxygen therapy attenuates neuropathic hyperalgesia in rats and idiopathic trigeminal neuralgia in patients

Eur J Pain. 2012 Sep;16(8):1094-105. doi: 10.1002/j.1532-2149.2012.00113.x.


Background: Neuropathic pain after nerve injury is severe and intractable, and current drug and non-drug therapies offer very limited pain relief. Hyperbaric oxygen (HBO 2) has been clinically used for protection of the nervous system after acute injury. We investigated whether HBO 2 treatment could prevent and/or attenuate neuropathic pain in animals and in patients.

Methods: Mechanical allodynia and thermal hyperalgesia and neurochemical alterations of neuropathic pain were analysed in male, adult, Sprague-Dawley rats with sciatic nerve injury. Clinical trials were conducted in patients with idiopathic trigeminal neuralgia.

Results: Repetitive HBO 2 treatment [a combination of pressure at 3 atmosphere absolute (ATA) and pure oxygen] greatly inhibited behavioural signs of neuropathic pain manifested as thermal hyperalgesia and mechanical allodynia. Such an HBO 2 treatment also inhibited nerve injury-induced induction of c-Fos and activation of astrocytes and increased phosphorylation of NR2B receptor and the subsequent Ca 2+-dependent signals in rats. Neither high pressure (up to 3 ATA) nor pure oxygen alone resulted in analgesic effect. In clinical trials, one course of HBO 2 therapy (10 consecutive days) produced a rapid-onset, dose-dependent and long-lasting analgesic effects evidenced by the decreased doses of carbamazepine required for keeping patient pain at a minimum and decreased scores of visual analogue scales, which was used for patient's self-evaluation.

Conclusions: These findings support that HBO 2 therapy is an effective approach for treating neuropathic pain in both animals and human beings and suggest that neural protection, anti-inflammation and inhibition of nerve injury-induced altered neural activity may contribute to the analgesic effect of HBO 2 therapy.

Publication types

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

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Hyperalgesia / metabolism
  • Hyperalgesia / therapy*
  • Hyperbaric Oxygenation*
  • Male
  • Neuralgia / metabolism
  • Neuralgia / therapy*
  • Pain Measurement
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sciatic Nerve / injuries
  • Spinal Cord / metabolism*
  • Treatment Outcome
  • Trigeminal Neuralgia / metabolism
  • Trigeminal Neuralgia / therapy*


  • Cyclic AMP Response Element-Binding Protein
  • NR1 NMDA receptor
  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Cyclic AMP
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Extracellular Signal-Regulated MAP Kinases