Effects of intracerebroventricular injection of vitamin B12 on formalin-induced muscle pain in rats: Role of cyclooxygenase pathway and opioid receptors

Introduction Muscle pain is a major clinical problem affecting nearly most of the world's population.1 Little is known about muscle pain because of the complexity of muscle nociception.2 To better understand the muscle pain mechanisms, different experimental pain models are used including intramuscular (IM) injection of carrageenan, acidic saline and formalin.2,3 In addition to peripheral modulation, supra-spinal pathways of pain such as descending pain modulation centers are involved in muscle pain mechanisms.4 Vitamin B12 is an essential water-soluble vitamin5 and has fundamental roles in the brain function at all ages and also in the prevention of central nervous system developmental disorders, mood disorders and dementia.6 Recently, vitamin B12 has been demonstrated to have potential effects on inflammatory and neuropathic pains in experimental and clinical studies.7,8 The cyclooxygenase pathway inhibition, the availability and effectiveness of noradrenaline and 5-hydroxytriptamine in the descending inhibitory nociceptive system may involve in analgesic effects of vitamin B12.7 Diclofenac, an acetic acid-type, non-steroidal antiinflammatory drug (NSAID), is commonly used as a potent pain killer exhibiting inhibitory actions on cyclooxygenase2 2 In addition to a local peripheral action on inflamed tissue; diclofenac also affects pain processing at the spinal and supra-spinal levels.10-13 Vitamin B12 and diclofenac affect each other function in producing analgesic effects. [...]it has been reported that local co-administration of vitamin B12 and diclofenac enhances diclofenac-induced antinociception and intraperitoneal (IP) co-injection of these chemicals increases vitamin B12-induced antinociception.10 It is well known that mu-, delta- and kappa-opioid receptors are widely distributed in the peripheral and nervous systems14 and play a central role in local, peripheral and central processings of pain.15 It has been reported that a non-specific antagonist of these receptors, naloxone, reverses the antinociceptive effect of diclofenac in acetic acid-induced visceral nociception in rats.12,13 Only in one study, it has been reported that prior microinjection of naloxone into the dorsal hippocampus prevents vitamin B12-induced antinociception in the formalin-induced orofacial pain.16 However, prior IP injection of naloxone did not prevent vitamin B complex (thiamine/pyridoxine/ cyanocobalamin)-induced antinociception in visceral and somatic pain models in rat