Effect of intrathecal Ketamine in prevention of Phantom limb pain following lower extremity amputation surgeries: A randomized clinical trial.

Phantom limb pain refers to thepresence of painful sensations in an absent limb parts and it has beenclassified as neuropathic pain syndrome[1-3]. The first medical description ofpost amputation sensation was given in 1552 by Ambroise Pare, a French militarysurgeon, who noticed that patients complain of severe pain in the missing limbfollowing amputation[4]. Phantom limb pain and sensations may have its onsetimmediately or years after the amputation. There are reports of two peakperiods of onset, the first within a month and the second a year afteramputation[5]. Generally, pain diminishes in both frequency and duration duringthe first 6 months after amputation[6].

Although 80% of patients mayexperience phantom limb pain after lower limb amputation[4, 7], its reportedincidence varies widely due to the absence of a unified definition of phantomlimb pain or to the fact that many patients don’t report their pain for fear ofbeing stigmatized as mentally ill.

The underlying mechanisms ofdevelopment of phantom limb pain are poorly understood, however major changesin both central and peripheral nervous system in response to peripheral nerveinjury and subsequent alterations in the peripheral sensory input arepostulated for the development of phantom sensations. Central sensitization,occurring at the level of spinal cord is likely to play a important role inongoing pain[8-10]. Animal models of peripheral nerve injury have shown thatactivation of the N-methyl D-aspartate (NMDA) receptor is integral to theprocess of central sensitization, particularly in nerve injury models[11,12].Laboratory studies implicate that sensory input from noxious stimuli at thetime of nerve injury with acute central neural plasticity leads to persistentneuropathic pain. NMDA antagonists administered to animals prior to nerveinjury significantly reduced behavioral signs of neuropathic pain andassociated neurochemical changes[13,14]. The mechanism of action is thought tobe prevention of spinal cord sensitization.

In a randomized study assessingthe effect of pre-emptively modulating sensory input with epidural ketamine onpost-amputation pain and sensory processing, Wilson and others demonstratedthat epidural ketamine didn’t affect significantly onset of phantom pain andstump pain after one year of observation. But postoperative analgesia wassignificantly better in ketamine group with reduced stump sensitivity[8]. Thisstudy defined role of NMDA receptors in the development of pain following amputation,but warrants further studies to confirm its role in persistent phantom limbpain.

              However, there is still no consensus onthe efficacy of NMDA receptor antagonist ketamine intrathecally on phantom limbpain and therefore the present study is undertakenIn this study, we assess the effect ofpre-emptive treatment with intrathecally administered NMDA antagonist, Ketaminein combination with local anaesthetic on reducing spinal sensory transmissiontriggering hyperplastic changes, acute central sensitization and thedevelopment of persistent phantom limb pain.