Long-Term High-dose Oral Morphine in Phantom Limb Pain Introduction
A man aged 75-year-old was shown to the hospital for malignant mesenchymal tumor of the upper one-third of right tibia. It was already diagnosed around 13 years ago and was found to have localized disease with negative positron emission tomography for any surrounding metastasis. He had his right leg removed (above knee). Postoperative pain was treated with epidural morphine at the dose of 3 mg bid for five days after the amputation and the pain was completely relieved. Post-discharge prescription involved oral dose of morphine (5 mg, four hourly), paracetamol (1000 mg, six hourly) and Bisacodyl (10 mg at bedtime). After seven days of discharge, the patient experienced radiating intense clutching pain, with occasional pins and needle sensations and heaviness in the limb.
The most likely diagnosis of this presentation is
Chronic phantom limb pain (PLP) refers to a hallucination that the patient experiences the existence of the limb after its been removed and also experiences the pain in the missing limb. Phantom limb pain is very common in all amputees.1 The incidence of PLP post-amputation varies from 49% to 88%. 2 Although the underlying pathophysiology is unclear, peripheral and spinal mechanisms are considered to play a role in pain modulation in amputees and also the central mechanisms are likely to be crucial.3 However, deafferentation can also produce similar symptoms.4 Previous findings have indicated that the amputation of the lower limb could alter the cortical representation of the missing limb and the underlying white matter connections.5
A general physical examination and the typical signs experienced by the patients were suggestive of chronic phantom limb pain (PLP). His pain score was 8 on a visual analog scale (VAS).
The treatment of PLP was started with oral morphine 10 mg/ four hours and the dose was gradually titrated to 120 mg/ four hours over a period of four weeks. After this treatment, the VAS score was 1-2, suggesting improvement in pain. He was asked to visit the hospital at least once in a month for next 12 months and the oral dose of morphine was continued. This stable dose of morphine offered 80-90% relief and 1-3 VAS score was noted. However, in a later visit, the patient complained of more intense pain and thus the dose of morphine was increased to 300 mg/ four hours. During the subsequent follow up, there was no significant improvement in the pain. Therefore, epidural analgesia with 0.125% bupivacaine infusion was employed for pain relief which provided optimum pain relief with no phantom sensations. Moreover, a chemical lumbar sympathectomy was considered under fluoroscopic guidance at the level of L2 with 4 ml of phenol, following which the patient experienced partial pain relief. A dose of morphine was gradually reduced to 240 mg/ four hours and the additional modalities like spinal cord stimulator, neuromodulator, and nerve blocks were undertaken as an additional treatment measures for next few years. To avoid drug addiction, dose of morphine was gradually withdrawn that caused rebound pain; however, there were no signs of addiction. Furthermore, results of tests (including verbal adult intelligence scale (VAIS), Bender-Gestalt test; Draw a person test and Rorschach inkblot test) revealed that the patient has average intelligence with cluster B and C traits, and ruled out possible drug-seeking behavior.
Phantom pain is often refractory to conventional pain relieving approaches and therefore it represents challenges while treating.4 However, deep brain stimulation has been proven to be effective. Accumulative studies have indicated that the transcranial magnetic stimulation (rTMS) can relieve chronic pain. Most of therapies for phantom limb pain are based on the idea that plastic changes after amputation are maladaptive and attempt to normalize representations of cortical areas adjacent to the hand area.6
In this case, the dose of morphine was gradually titrated to its optimal range that offered pain relief. Earlier evidences have reported a need of high-dose morphine in the management of PLP. Due to its unclear physiology, treatment of PLP remains challenging. Approaches to treat PLP may include drugs and medications like NSAIDs, opioids, antiepileptic, antidepressants and non-pharmacological approaches like TENS, sympathectomy, deep brain stimulation and motor cortex stimulation. Opioids are proven to be effective the treatment of PLP and hypothesized to influence cortical reorganization.2
Morphine addiction is complicated and is characterized by having craving, loss of control over the substance use and compulsion to use drugs despite its well-known hazards. However, the rate of addiction in cancer patients is <1% after taking opioid medications. Increased pain severity and resumption of previous dose causing significant pain relief are suggestive of high-dose requirement.2 In this case the patient was stable on current dose (540 mg of oral morphine every four hours) for the last seven years without any signs of addiction and the patient continued his routine daily activities and depression was well controlled with medications.
Detailed assessment of pain along with analgesic titration plays a critical role in cancer pain management. If received under close observation and dose titration, addiction has not been found with morphine in PLP even at a dose of 300 mg/ four hours.
Croci D, Fandino J, Marbacher S. Phantom Radiculopathy: Case Report and Review of the Literature. World Neurosurg. 2016 Feb 9. pii: S1878-8750(16)00217-5.
Kumar V, Garg R, Bharati SJ, Gupta N, Bhatanagar S, Mishra S, et al. Long-term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk. Indian J Palliat Care. 2015 Jan-Apr;21(1):85-7.
Lee JH, Byun JH, Choe YR, et al. Successful Treatment of Phantom Limb Pain by 1 Hz Repetitive Transcranial Magnetic Stimulation Over Affected Supplementary Motor Complex: A Case Report. Ann Rehabil Med. 2015 Aug;39(4):630-3.
Jin QQ, Tang DD, Peng WW, Hu L. [The Research Advances of the Pathomechanism of Phantom Limb Pain (PLP)]. Sheng Li Ke Xue Jin Zhan. 2015 Oct;46(5):341-6.
Jiang G, Yin X, Li C, et al. The Plasticity of Brain Gray Matter and White Matter following Lower Limb Amputation. Neural Plast. 2015;2015:823185.
Raffin E, Richard N, Giraux P, Reilly KT. Primary motor cortex changes after amputation correlate with phantom limb pain and the ability to move thephantom limb. Neuroimage. 2016 Feb 11;130:134-144.