Effects of intracerebroventricular injection of vitamin B(12 )on formalin-induced muscle pain in rats: Role of cyclooxygenase pathway and opioid receptors

Vitamin B(12) modulates pain at the local and peripheral levels. This study has investigated the effects of intracerebroventricular (ICV) injection of vitamin B(12 )on themuscle pain. We used diclofenac (cyclooxygenase inhibitor) and naloxone (opioid receptors antagonist) to clarify the possible mechanisms. For ICV injections, a guide cannula was implanted in the left lateral ventricle of the brain. Muscle pain was induced by intramuscular injection of formalin (2.50%; 50 µl) in the right gastrocnemius muscle and the number of paw flinching was recorded at 5-min blocks for 60 min. Locomotor activity was performed using an open-field test. Formalin induced a biphasic pain. Vitamin B(12 )(1.25, 2.50, 5.00 and 10.00 µg per rat) and diclofenac (12.50 and 25.00 µg per rat) significantly reduced both phases pain intensity. Significant antinociceptive effects were observed after combined treatments of diclofenac (6.25 and 12.50 µg per rat) with vitamin B(12) (0.63 and 2.50 µg per rat), respectively. Prior ICV injection of naloxone (10.00 µg per rat) prevented vitamin B(12) (10.00 µg per rat) and diclofenac (25.00 µg per rat) induced antinociceptive effects. All the above-mentioned chemicals did not alter locomotor behavior in an open-field test. The present results showed that the cyclooxygenase pathway and opioid receptors may be involved in the central antinociceptive effect of vitamin B(12). In addition, opioid receptors might be involved in diclofenac-induced antinociception.