Evaluation of Antinociceptive and Neurotoxic Effects of Intrathecal Dexmedetomidine in Rats

Abstract

Objective: Dexmedetomidine has been reported to produce analgesia after intrathecal administration. In the present study the α2-adrenoceptor agonist dexmedetomidine was evaluated for its potential spinal neurotoxic effects.Material and Methods: Three days after intrathecal cannulation, rats were administered either dexmedetomidine (3 μg/30 μL, i.t.) or saline (30 μL, i.t.). Antinociceptive, sedative and motor effects of intrathecal administrations of dexmedetomidine or saline were evaluated during 90 min. The tail-flick and hot plate tests were used to assess the thermal nociceptive threshold. Seven days after drug administration, animals were sacrified and spinal cords were evaluated for histopathological changes by light microscopy.Results: Dexmedetomidine administered intrathecally produced antinociception. Antinociception was accompanied by immediate sedation and loss of placing-stepping reflexes that lasted over 40 min in all dexmedetomidine administered rats. In all rats, microscopic examination revealed mild gliosis and minimal infiltration of inflamatory r cells in posterior white matter. Mild (total score 4-6) histopathologic lesions were seen in four animals in dexmedetomidine adminisered rats, but there was no statistically significant difference when compared with the saline administered rats. Conclusion:We observed that intrathecal injections of dexmedetomidine at the dose of 3 μg/30 μL produce antinociception but did not cause any histopathological sign of injury in the spinal cord.

Evaluation of the neurotoxicity of intrathecal dexmedetomidine on rat spinal cord (electromicroscopic observations)

“…'s study, intrathecal injections of dexmedetomidine at the dose of 10 μgr-1 produce antinociception but did not cause any histopathological sign of injury in the spinal cord. [ 25 ]…”

“…Konakci et al . [ 25 28 ] reported moderate or severe demyelinization of myelin sheaths in the white matter when 10 μg dexmedetomidine was administered through the epidural route. This dose was the same dose used in the present study.…”

Comparative evaluation of intrathecal morphine and intrathecal dexmedetomidine in patients undergoing gynaecological surgeries under spinal anaesthesia: A prospective randomised double blind study

“…Animal studies have been conducted with intrathecal dexmedetomidine in dose range of 2.5–100 µg, however, risk of neurotoxicity cannot be denied at dosage more than three µg. [ 12 13 14 ] Human studies have shown that 3–15 µg of dexmedetomidine co-administered with local anaesthetics has a dose-dependent effect on anaesthesia, analgesia and haemodyanamic stability. [ 5 15 16 17 18 ] Similar results were seen with other α 2 AR agonist, clonidine, in doses of 15–45 µg when added to intrathecal local anaesthetic.…”

Combined Use of Intrathecal Opioids and Dexmedetomidine in the Management of Neuropathic Pain

“…Dexmedetomidine is a potent and highly selective alpha 2-adrenoceptor agonist. Although dexmedetomidine has a number of undesirable side effects (diuresis, mydriasis, and sedation), intrathecal administration of dexmedetomidine has antinociceptive effects in animals [ 5 ]. Hence, a combination of several agents that produce synergistic interactions or similar therapeutic effects may also attenuate the undesired effects by permitting a diminution dose of individual agents to be administered.…”