Systematic administration of B vitamins attenuates neuropathic hyperalgesia and reduces spinal neuron injury following temporary spinal cord ischaemia in rats

Eur J Pain. 2014 Jan;18(1):76-85. doi: 10.1002/j.1532-2149.2013.00390.x. Epub 2013 Sep 5.

Abstract

Background: B vitamins have been demonstrated to be effective in treating chronic pain due to peripheral nerve injury. We investigated whether B vitamins could alleviate neuropathic pain and reduce neuron injury following temporary ischaemia in a rat model of spinal cord ischaemia-reperfusion injury (SCII).

Methods: SCII was produced by transiently blocking the unilateral lumbar arteries in adult male Sprague-Dawley rats. Behavioural and neurochemical signs of neuropathic pain and spinal neuron injury were analysed with and without B vitamin treatment.

Results: SCII caused behavioural thermal hyperalgesia and mechanical allodynia and neurochemical alterations, including increased expression of the vanilloid receptor 1 (VR1) and induction of c-Fos, as well as activation of the astrocytes and microglial cells in the spinal cord. Repetitive systemic administration of vitamin B complex (B1/B6/B12 at 33/33/0.5 mg/kg, i.p., daily, for 7-14 consecutive days) significantly reduced thermal hyperalgesia and the increased expression of VR1 and c-Fos, as well as activation of the astrocytes and microglial cells. SCII caused a dramatic decrease of the expression of the rate-limiting enzyme glutamic acid decarboxylase-65 (GAD65), which synthesizes γ-aminobutyric acid (GABA) in the axonal terminals, and β-III-tubulin, and also caused loss of Nissl bodies in the spinal cord. These alterations were largely prevented and rescued by the B vitamin treatment.

Conclusions: These findings support the idea that the B vitamins are capable of neuroprotection and antinociception during spinal cord injury due to temporary ischaemia. Rescuing the loss of inhibitory GABAergic tone may reduce spinal central sensitization and contribute to B vitamin-induced analgesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Glutamate Decarboxylase / metabolism
  • Hot Temperature
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Immunohistochemistry
  • Male
  • Motor Activity / drug effects
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Neurons / drug effects*
  • Neurons / pathology
  • Nissl Bodies / drug effects
  • Physical Stimulation
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / pathology
  • Spinal Cord Ischemia / complications*
  • Spinal Cord Ischemia / pathology
  • Tubulin / biosynthesis
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / therapeutic use*

Substances

  • Proto-Oncogene Proteins c-fos
  • Tubulin
  • Vitamin B Complex
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2